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May 2016 • Volume 18, Supplement 1
The Official Publication of the Consortium of Multiple Sclerosis Centers
2016 Annual Meeting of the CMSC
Abstracts from the 30th Annual Meeting of the Consortium of Multiple Sclerosis Centers 1 June 2016 to 4 June 2016 National Harbor, Maryland ijmsc.org
Photo courtesy of EMSP’s Under Pressure Project. Photo Credit: Lurdes R. Basoli.
At Sanofi Genzyme, we believe that when we know more, we can do more. The vs.MS global survey revealed that the MS Community is struggling. It’s time to get real about disability – what it looks like, how it can be seen and felt, and what can be done to better delay it.
A global initiative that aims to shed light on and address the true physical and emotional impact of MS on people living with the disease and their
Declare yourself vs.MS and encourage your patients to learn more at www.vs-MS.com. Together, we can strengthen the voice of the MS Community and reimagine our expectations of life with MS.
care partners #vsMS
@SanofiGenzyme
@SanofiGenzyme
A Closer Look At The
Survey Results
Emotional Burden
Nearly 1/2 of respondents living with RMS feel limited by their depression or anxiety
More than 2/3 of respondents living with RMS said most people around them don’t know they have MS because their symptoms are invisible
Relationships & Intimacy
Nearly 1/2 of respondents do not feel as sexually attractive since their RMS diagnosis
1/3 of respondents living with RMS go out of their way to keep their MS private and hidden
More than 1/2 of single respondents worry that their RMS will impact their ability to find a partner
Effect on Cognition
More than 1/2 of respondents living with RMS find issues with memory to be limiting on their daily activities
More than 1/2 of respondents living with RMS said their ability to process information has slowed down
More than 1/2 of respondents living with RMS often have difficulties concentrating and remembering things
of respondents living with RMS reported that what matters most to them is taking action to prevent progression and potential disability
About the vs.MS Survey
More than 1/2 of respondents living with RMS feel lonely or isolated because of their MS
Effect on Career
More than 45% of respondents living with RMS feel they now have trouble making decisions
2/3 of respondents living with RMS said their MS affected their ability to keep their job
More than 1/4 of respondents living with RMS have difficulty completing assignments at work due to their MS
1/2 of respondents feel their ability to progress in their career has changed for the worse since they were diagnosed with RMS
Physical Symptoms
Disability & Progression
Nearly 1/2 of RMS care partners do not discuss their fear of MS progressing to avoid upsetting the person they care for
Nearly 1/2 of respondents living with RMS feel guilty or upset with how their symptoms and disabilities affect others around them
Nearly 3/4 of respondents living with RMS believe the treatment decisions they make now will impact their disease activity and disability level later in life
More than 1/2 of respondents living with RMS feel that their physical functioning has worsened since their diagnosis
1,075
PEOPLE LIVING WITH RMS
7
580
RMS CARE PARTNERS
COUNTRIES (U.S., CA, FR, IT, UK, SP, & AU)
More than 3/4 of respondents living with RMS feel fatigue is limiting on their daily activities, even when they get enough sleep
More than 1/3 of respondents feel urinary problems associated with their RMS are a factor in the decisions they make when planning to leave the house
More than 40% of respondents living with RMS are unable to do housework or chores because of their fatigue
SURVEY CONDUCTED FROM
JULY THROUGH AUGUST 2015
DEVELOPED BY SANOFI GENZYME WITH INPUT & GUIDANCE FROM
GLOBAL STEERING COMMITTEE
OF LEADING NEUROLOGISTS
Editorial Board
May 2016 • Vol. 18, Suppl. 1
Editor in Chief Francois Bethoux, MD Cleveland Clinic Cleveland, Ohio, USA Ex Officio June Halper, MSN, ANP, FAAN Hackensack, New Jersey, USA Project Manager Maria Stadtler, CCRP Cleveland Clinic Cleveland, Ohio, USA Board Members Ted Brown, MD, MPH Evergreen Neuroscience Institute and Medical Center Kirkland, Washington, USA Susan Coote, PT, PhD University of Limerick Limerick, Ireland Mary Filipi, PhD, ARNP University of Nebraska Medical Center Omaha, Nebraska, USA Marcia Finlayson, PhD, OT Reg (Ont), OTR Queen’s University Kingston, Ontario, Canada Frederick W. Foley, PhD Yeshiva University Bronx, New York, USA Holy Name Medical Center Teaneck, New Jersey, USA Kathleen Fuchs, PhD University of Virginia Health System Charlottesville,Virginia, USA Eduard Gappmaier, PT, PhD University of Utah Salt Lake City, Utah, USA Christoph Heesen, MD Institute of Neuroimmunology and Clinical MS Research University Medical Center Hamburg, Germany James Marriott, MD, FRCPC University of Manitoba Winnipeg, Manitoba, Canada Lori Mayer, MSN, DNP(s), MSCN, CCRP MS Clinic of Central Texas Round Rock, Texas, USA Sarah Morrow, MD, MSc, FRCPC University of Western Ontario London Health Sciences Centre London, Ontario, Canada Jacob J. Sosnoff, PhD University of Illinois at Urbana-Champaign Urbana, Illinois, USA Megan Weigel, DNP, ARNP-c Baptist Medical Center Jacksonville Beach, Florida, USA
2016 Annual Meeting of the CMSC
W
e are pleased to present this supplement to the International Journal of MS Care (IJMSC) containing the abstracts from the 2016 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), held from June 1 through 4, 2016, in National Harbor, Maryland (within the Washington, DC, area). These abstracts include platform, poster, and Whitaker Research Track presentations delivered at the meeting. If you were not able to attend the conference, this is a wonderful opportunity for you to appreciate the diversity and depth of this outstanding group of presentations. The print version of this supplement is being distributed at the CMSC meeting in National Harbor to meeting attendees. The electronic version, which is available to all on the IJMSC website at ijmsc.org, can be searched using key words to identify abstracts on topics of individual interest. We would like to thank Sanofi Genzyme for their support, which made this publication possible. We hope that this material will assist you in your care of MS patients and stimulate your interest in furthering research and care in MS. —Francois Bethoux, MD Editor in Chief
Mary Alissa Willis, MD Cleveland Clinic Cleveland, Ohio, USA Publishers Joseph J. D’Onofrio Frank M. Marino Delaware Media Group 66 S. Maple Ave., Ridgewood, NJ 07450 201-612-7676
[email protected] Managing Editor Annette Theuring Art Director James Ticchio
Cover photo credit: Sean Pavone / Thinkstock
International Journal of MS Care iv
RMS=relapsing forms of multiple sclerosis.
QUIETING MS Quietly *
for your patients with relapsing MS
* AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Overall discontinuation rates due to adverse events were 12.5% with AUBAGIO 14 mg, 11.2% with AUBAGIO 7 mg, and 7.5% with placebo, and treatment discontinuation rates due to common adverse events were ≤3.3% in the pooled clinical trials.1,2 MS=multiple sclerosis.
INDICATION AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis. IMPORTANT SAFETY INFORMATION WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. AUBAGIO is contraindicated in patients with severe hepatic impairment and in patients taking leflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If druginduced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO. Based on animal data, AUBAGIO may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting AUBAGIO. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment or prior to the completion of an accelerated elimination procedure after AUBAGIO treatment.
Warnings and Precautions Patients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine). Before starting therapy, use of reliable contraception must be confirmed, and the patient counseled on risks to the fetus. Patients with delayed onset of menses or other reason to suspect pregnancy should immediately see their physician for pregnancy testing. Patients who become pregnant or wish to become pregnant should discontinue treatment, followed by accelerated elimination until plasma concentrations of 60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination. Interstitial lung disease and rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with leflunomide; a similar risk would be expected for teriflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and use accelerated elimination. Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.
Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%). Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters. Use in Specific Populations: AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use reliable contraception. Men wishing to father a child should discontinue therapy and undergo accelerated elimination, with verification of plasma concentrations 26.5). Participants completed surveys of the Hospital Anxiety and Depression Scale (HADS), Tampa Scale for Kinesiophobia (TSK), and Pain Catastrophizing Scale (PCS). Separate multinomial logistical regressions evaluated the differences between pain groups on psychosocial factors. Results: No pain was reported by 37.7% of the sample, 31.1% reported pain with low PI (n = 19), and 31.1% reported pain with high PI (n = 19). Pain with high PI was associated with higher reporting of all psychosocial factors compared to no pain (TSK OR = 1.19, 95% CI = 1.06-1.32; PCS OR = 1.10, 95% CI = 1.04-1.17; depression OR = 1.42, 95% CI = 1.16-1.73; anxiety OR = 1.35, 95% CI = 1.13-1.62) and pain with low PI (TSK OR = 1.16, 95% CI = 1.04-1.29; PCS OR = 1.07, 95% CI = 1.01-1.13; depression OR = 1.29, 95% CI = 1.08-1.54; anxiety OR = 1.23, 95% CI = 1.04-1.46). Within catastrophizing, pain with high PI was associated with higher rumination, magnification, and helplessness compared to no pain, and pain with high PI was associated with higher helplessness compared to those in pain
International Journal of MS Care 20
Posters: Cognition, Depression, and Psychosocial Issues with low PI. Conclusions: Higher levels of pain interference were associated with higher levels of kinesiophobia, catastrophizing, depression, and anxiety. Future research should evaluate the efficacy of targeting these modifiable factors to reduce the pain experience in people with MS. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Annalisa F. Sciullo, Carly A. Solon: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Elizabeth K. Seng: International Headache Academy (grant/research support). Keywords: Psychological issues and MS (CG10) Preliminary Comparison of Baseline Cognition and Correlations with Patient-Reported Outcomes of Fingolimod Versus Glatiramer Acetate in Multiple Sclerosis Patients in a Longitudinal Observational Study Brian D. Hoyt,1 Justin Honce,2 Stefan Silau,3 Brittany Wedeman,3 Eric Engebretson,3 Kristen Johnson,4 Nadia Tenenbaum,5 Vivian Herrera,4 Lisa Siconolfi,5 Enrique Alvarez,3 Kavita Nair6 Neurology/Neurosurgery, University of Colorado School of Medicine, Aurora, CO; Radiology, University of Colorado School of Medicine, Aurora, CO; 3Neurology, University of Colorado School of Medicine, Aurora, CO; 4Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ; 6University of Colorado School of Pharmacy, Aurora, CO 1 2
Background: Stable relapsing multiple sclerosis (MS) patients who are long-term users of fingolimod (FTY) and glatiramer acetate (GA) have few if any signs of inflammation. However, their brain atrophy rates are unknown. Measures of brain atrophy, cognition, patient-reported outcomes (PROs), and their interrelationships may provide insight into subclinical disease progression and whether it differs between disease-modifying therapies. Objectives: Compare baseline cognitive characteristics and describe correlations between Neuro-QoL scales and cognitive tests in a cohort of stable relapsing MS patients on FTY or GA enrolled in a prospective 2-year study examining brain volume, cognition, and PROs. Methods: Relapsing MS patients aged 18–60 years on FTY or GA for >2 years were identified and will be followed for 2 years with a baseline visit and subsequent annual visits including magnetic resonance imaging (MRI), cognitive testing, and the NeuroQoL. In this analysis, baseline performance was compared on measures of attention/processing speed, executive function, and memory on the following tests: Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Verbal Fluency (VF), California Verbal Learning Test-II (CVLTII), Brief Visuospatial Memory Test-Revised (BVMT-R). An analysis of baseline cognitive characteristics by treatment arm and correlations between Neuro-QoL scales and cognitive tests for all currently enrolled patients is presented. Results: For this analysis, 45/60 planned FTY and 25/60 planned GA patients had completed a baseline visit. No group differences were found for demographic or disease characteristics (disease duration, Expanded Disability Status Scale [EDSS], or normalized brain volume). Similarly, no group differences were found on the cognitive measures (all P > .05). For all patients, PASAT, SDMT, and VF correlated with NeuroQoL general cognition and executive function scales (all P < .05). Correlations between CVLT-II and BVMT-R and the NeuroQoL general cognition scale approached significance (P = .06). The NeuroQoL fatigue scale was negatively correlated with VF (P = .01). Conclusions: Preliminary analysis suggests that stable long-term users of FTY and GA are comparable on measures of cognition. Performance on all objective cognitive measures was correlated with subjective selfreport of cognitive concerns. This comparison will help determine whether future differences over the 2-year study period can be attributed to type of therapy or other group differences. Supported by: Novartis Pharmaceuticals Corporation Disclosure: Brian D. Hoyt, Justin Honce, Stefan Silau, Enrique Alvarez: Novartis Pharmaceuticals Corporation (grant/research support). Brittany Wedeman, Eric Engebretson: Nothing to disclose. Kristen Johnson, Nadia Tenenbaum, Vivian Herrera, Lisa Siconolfi: Novartis Pharmaceuticals Corporation (employee). Kavita Nair: Novartis Pharmaceuticals Corporation, Genentech, Astellas, Eli Lilly (grant/research support). Keywords: Cognition and MS, Psychological issues and MS
(CG11) Discrete Norms and Regression-Based Formulae for Interpreting the Minimal Assessment of Cognitive Function in Multiple Sclerosis: A Canadian Normative Study David P. Marino,1,2 Jason A. Berard,1,3 Denis Cousineau,3 Anthony Feinstein,4 Sarah A. Morrow,5 Lisa A.S. Walker1 The Ottawa Hospital Research Institute, Ottawa, ON, Canada; 2University of Toledo, Toledo, OH; 3University of Ottawa, Ottawa, ON, Canada; 4Psychiatry, University of Toronto, Toronto, ON, Canada; 5Western University, London, ON, Canada 1
Background: The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS; Benedict et al., 2002) is a consensusbased collection of neuropsychological tests designed to evaluate cognitive dysfunction in individuals with multiple sclerosis (MS). Because the MACFIMS comprises different tests, it is typically scored using each respective published test manual, leaving the examiner to make test interpretations from norms derived from different populations. Objectives: The goal of this study was to co-norm the MACFIMS tests to allow for improved psychometric interpretation. Methods: This study aggregated MACFIMS data sets from across three Canadian cities (Ottawa, Toronto, London), yielding a total of 330 healthy control participants from four different studies evaluating cognition in individuals with MS. Results: From these data traditional age-based discrete norms were derived. In addition, regression-based formulae controlling for demographics (sex, age, education) were established for ease of use in a clinical setting. The various demographic variables varied in their contribution to each MACFIMS test in the regression models, predicting 0% to 18% of the variance. Conclusions: Provision of these regression-based formulae will allow for more accurate interpretation of MACFIMS scores by allowing clinicians to correct for all relevant demographic variables simultaneously, leading to improved clinical decision making for individuals with MS. The provision of both discrete and regressionbased options will allow clinicians the freedom to choose the scoring method best suited to their practice. Supported by: Multiple Sclerosis Society of Canada, University of Ottawa Brain and Mind Research Institute, Novartis Canada Disclosure: Nothing to disclose Keywords: Psychological issues and MS (CG12) “You Need to Strategize and You Also Need Recommendations, Advice, and Counsel from Others.” Disability Income Insurance: Perspectives of People with Multiple Sclerosis and Care Partners Mary Beth Mercer,1 Paul Ford,1 Deborah M. Miller2 Bioethics, Cleveland Clinic, Cleveland, OH; 2Mellen Center, Cleveland Clinic, Cleveland, OH 1
Background: There has been considerable change in the personal insurance environment since the last comprehensive insurance survey of people with multiple sclerosis (PwMS) was conducted. The Affordable Care Act has been a boon in terms of access, but many individuals have found it cost prohibitive with regard to copays and deductibles. Since the economic downturn of 2008, many PwMS, like the rest of the working population, have experienced loss of or reduction in work, the primary source of disability income, long-term care, and life insurances. In order to gain a greater understanding of the personal insurance environment and the related changes in coverage, concerns, and consequences that occur, we plan to conduct a national survey with PwMS. The first step in this process is to conduct focus groups with PwMS to inform the development of this national survey. Methods: Focus groups were conducted to explore the views and experiences of people with MS and care partners with regard to health, life, long-term care, and disability insurances. Constant comparative analysis was used to identify themes within the narratives. Results: Thirty-six people with MS and 24 partners participated in 8 focus groups conducted at 4 National Multiple Sclerosis Society chapters in geographically distinct regions. Of those with MS, 75% are female and 81% are white, with a mean age of 53 years; 50% are employed and 55% have disability income insurance. Three-quarters of care partners are spouses, 96% are white,
International Journal of MS Care 21
Posters: Cognition, Depression, and Psychosocial Issues 50% are female, and their mean age is 60. Three themes related to disability income insurance emerged that are broadly grouped as burden, subtle symptoms, and applications denial. Participants perceive the initial application and appeals processes as burdensome and stressful in terms of effort, uncertainty of outcome, and duration. Some disabilities resulting from MS are not always readily apparent (eg, fatigue and cognitive impairment) and may be difficult to demonstrate to prove eligibility even though they impact job attendance and performance. Furthermore, participants perceive that most initial applications are denied and that the manner in which applications are completed is of utmost importance in determining eligibility decisions. Thus, they recommend that applicants seek legal assistance to increase the likelihood of approval yet recognize that cost may be a barrier to accessing legal services. Conclusions: These data will help ensure that the insurance survey we conduct will address matters important to PwMS and their families. Supported by: National Multiple Sclerosis Society Disclosure: Mary Beth Mercer, Paul Ford: Nothing to disclose. Deborah M. Miller: Biogen Idec (receipt of intellectual property rights/patents). Keywords: Disability insurance, Employment in MS (CG13) Differences in Pain, Pain-Related Physical and Emotional Functioning, and Multiple Sclerosis (MS)– Related Impairment by the Number of Pain Locations in MS Elizabeth S. Gromisch,1,2 Robert D. Kerns,2,3 Rebecca Czlapinski,3 Beth Beenken,1,2 John Otis,4,5 John Beauvais1,2 Department of Psychology, VA Connecticut Healthcare System, West Haven, CT; Yale University School of Medicine, New Haven, CT; 3Pain Research, Informatics, Multimorbidities and Education (PRIME) Center, VA Connecticut Healthcare System, West Haven, CT; 4Research Service, VA Boston Healthcare System, Boston, MA; 5Boston University, Boston, MA 1 2
Background: Between 13% and 80% of patients with multiple sclerosis (MS) experience pain that is commonly associated with functional difficulties, emotional distress, and decreased quality of life. MS-related pain is associated with multiple body parts and includes back pain, spasticity in the extremities, and facial/head pain associated with optic neuritis and trigeminal neuralgia. Objectives: This study examined differences in the experience of pain and its impacts by number of pain sites among persons with MS. It was hypothesized that persons with evidence of widespread pain would report greater pain and pain- and MS-related interference with physical and emotional functioning. Methods: Data were collected as part of a randomized clinical trial of cognitive-behavioral therapy for MS-related pain. Twenty-five participants completed the baseline evaluation, including self-reports of severity and location, pain-related physical functioning (West Haven-Yale Multidimensional Pain Inventory), and emotional functioning (Profile of Mood States and Beck Depression Inventory-Second Edition), and measures of MS-related functional status (MS Functional Composite). Participants were categorized into one of two groups by the number of pain locations, which was determined by quartiles. A P value of .1 was chosen due to the low sample size. Results: Participants with five or more pain locations endorsed greater fatigue (P = .039) and depressive symptomatology (P = .055). They were also engaged in more activities away from home (P = .027) than participants with four or fewer pain locations. There were no significant differences between the two groups in terms of their pain severity (P = .626), numbers of years of pain (P = .944), disease duration (P = .408), age (P = .501), or performance on the MS Functional Composite (P = .626). Conclusions: While the sample size was low, our findings suggest that persons with MS who had pain in more locations experience greater fatigue and depression even though they did not report greater pain severity or duration. Their engagement in more outside activities than participants with fewer pain locations suggests that while having pain in more locations may affect energy and mood symptoms, it may not necessarily interfere with their ability to engage in instrumental activities. Future research should more closely examine the relationship between pain and emotional functioning, and the hypothesis that
negative mood may mediate the spread of pain to other body sites among persons with MS. Supported by: VA RR&D D4150R, VA HSR&D 13-407 Disclosure: Nothing to disclose Keywords: Management of activities of daily living in MS, Pain and MS, Psychological issues and MS (CG14) Development and Validation of the MS Resiliency Scale Elizabeth S. Gromisch,1,2 Jessica H. Sloan,3 Vance Zemon,3 Tuula Tyry,4 Laura C. Schairer,5 Stacey Snyder,6 Frederick W. Foley3,7 Department of Psychology, VA Connecticut Healthcare System, West Haven, CT; 2Yale University School of Medicine, New Haven, CT; 3Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 4Dignity Health, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; 5VA NY Harbor Healthcare System, New York, NY; 6Mount Sinai Hospital, New York, NY; 7Holy Name Medical Center, Teaneck, NJ 1
Background: Resiliency is the most common pattern of adjustment, in which an individual is able to keep a relatively healthy and stable level of psychological and physical functioning after a traumatic experience. Factors such as hope, adaptive coping styles, physical activities, social support, and emotional awareness have been associated with resiliency. For some individuals, having a major medical diagnosis such as multiple sclerosis (MS) may be a traumatic experience. While several measures of resiliency have been developed, few measures focus on chronic illness and none are MS-specific. Objectives: This study aimed to develop and validate the MS Resiliency Scale (MSRS), a 75-item questionnaire with five proposed subscales that incorporate the different aspects involved in resiliency: 1) Hopefulness and Optimism, 2) Physical Well-Being, 3) Cognitive Processes, 4) Emotional Management, and 5) Support System. Methods: Participants (N = 1038) were individuals with MS who were recruited through the North American Research Committee on Multiple Sclerosis (NARCOMS) who completed the survey online; 106 participants were removed from the analyses due to missing data. The Resiliency Scale and Hospital Anxiety and Depression Scale (HADS) were used to establish convergent and divergent validity. Principal component analysis was run to determine the subscales. Results: Using a promax rotation with Kaiser normalization, and suppressing items with coefficients below 0.3, five subscales emerged that accounted for 42.75% of the variance. Each subscale had high reliability (internal consistency): Emotional and Cognitive Strategies (14 items; α = .947), Physical Well-Being (3 items; α = .765), Information Seeking (2 items; α = .730), Social Support (5 items; α = .813), and Spirituality (2 items; α = .859). Four of the subscales were weakly to moderately and significantly correlated with each other (r range: .106–.413). The exception was the Spirituality and Physical Well-Being subscales, which was nearly significant (r = .061, P = .068). The total score was positively correlated with the Resiliency Scale (r = .637, P < .0005), and negatively correlated with HADS Depression (r = –.724, P < .0005) and Anxiety (r = –.561, P < .0005). Conclusions: The 26-item MSRS provides clinicians with valuable information on patients’ adjustment to their MS. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Elizabeth S. Gromisch, Jessica H. Sloan, Vance Zemon, Tuula Tyry, Laura C. Schairer, Stacey Snyder: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Management of activities of daily living in MS, Psychological issues and MS (CG15) The Effects of Reward and Incentive on Performance on the Symbol Digit Modalities Test in Multiple Sclerosis Gabriel Hoffnung,1 Nicholas A. Vissicchio,1 Jeffrey G. Portnoy,1 Caroline Altaras,1 Lisa Glukhovsky,1 Mary Ann Picone,2 Frederick W. Foley1 Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ 1
Background: The Symbol Digit Modalities Test (SDMT) is one of the most commonly used measures in the evaluation of cognition in multiple sclerosis (MS); it is generally regarded as a measure of processing speed. Effort is an important component in the measure-
International Journal of MS Care 22
Posters: Cognition, Depression, and Psychosocial Issues ment of cognitive performance, and the role of motivation in effort is well established. Objectives: To examine the effect of a reward paradigm on patient performance on the SDMT in MS. Methods: This research is being conducted as part of a large, ongoing study at the MS center of Holy Name Medical Center in Teaneck, NJ. 20 patients with definite MS have been recruited so far (current to the date of submission of this abstract). The study is being carried out using the SDMT, a well-validated cognitive measure in MS. Each patient is being administered the SDMT twice with approximately 3 to 5 minutes between each administration. The two administrations of the SDMT include a monetary reward condition, wherein performance is incentivized through financial reward, and a control condition, with no reward offered for performance. Individual performance on the SDMT is being compared between the reward and no reward administration. Counterbalancing is being employed to control for learning effects. Results: Mean (SD) for total scores on all SDMT trials (N = 40) was 53.1 (14.5). Mean total scores for the control trial (n = 20) and the reward trial (n = 20) of the SDMT were 52.4 (13.9) and 53.6 (14.2), respectively. This difference was not significant (t = –1.035, P= .314). Conclusions: Results are preliminary, due to the small sample size; however, the reward paradigm appears to have no significant effect on performance. It appears that the function measured by total performance on the SDMT is relatively stable in response to reward/incentive-based motivation. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Gabriel Hoffnung, Nicholas A. Vissicchio, Jeffrey G. Portnoy, Caroline Altaras, Lisa Glukhovsky, Mary Ann Picone: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Multiple sclerosis, Cognition, Motivation, Reward, SDMT (CG16) The Effects of Learning on Cognitive Fatigue in Multiple Sclerosis Gabriel Hoffnung,1 Nicholas A. Vissicchio,1 Jeffrey G. Portnoy,1 Eliana Pasternak,1 Lisa Glukhovsky,1 Mary Ann Picone,2 Frederick W. Foley1 Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ 1
Background: Both cognitive and fatigue symptoms are highly common in multiple sclerosis (MS), and complaints of cognitive fatigue are also common. Learning is known to enhance performance, though not necessarily to overcome fatigue. Objectives: To measure learning effects on a measure of cognitive fatigue in MS. Methods: This research is being conducted as part of a large, ongoing study at the MS center of Holy Name Medical Center in Teaneck, NJ. 38 patients with definite MS have been recruited so far (current to the date of submission of this abstract). The study is being carried out using the Symbol Digit Modalities test (SDMT), a well-validated cognitive measure in MS. Each patient is being administered the SDMT twice with approximately 3 to 5 minutes between each administration. Fatigue in this study is being operationalized as the difference in performance on the SDMT between the first 30 seconds (30″) and the final 30 seconds (90″) of a 90-second administration. Learning is operationalized as performance on administration 2 as compared to administration 1. A mixed between-within (group × time) analysis of variance was performed to compare fatigue between the two administrations. Results: Mean (SD) for total scores on all SDMT trials (N = 74) was 54.6 (12.4). Mean total score for trial 1 (n = 37) and trial 2 (n = 37) of the SDMT were 52.6 (11.8) and 56.5 (12.8), respectively. Mean score for the 30″ interval was 20.25 (4.39) for the total sample and 19.54 (4.05) and 20.97 (4.65) for trials 1 and 2. Mean score for the 90″ interval was 17.20 (4.01) for the total sample and 16.72 (4.56) and 17.67 (4.05) on trials 1 and 2. A significant fatigue effect (30″ vs. 90″) was noted in the total sample (t = 10.956, P < .001) as well as on trials 1 and 2 (t = 6.799, P < .001; t = 8.783, P < .001). Learning effects were significant between trials 1 and 2 on total score (t = –5.408, P < .001), as well as at 30″ and 90″ (t = –4.498, P < .001; t = –2.697, P = .011). However, there was no significant group × time effect (Wilks lambda = .987, F = .475, P = .624). Conclusions: While learning has a significant effect on performance, and the learning effect on performance is present throughout task duration, learning does not significantly affect fatigue.
Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Gabriel Hoffnung, Nicholas A. Vissicchio, Jeffrey G. Portnoy, Eliana Pasternak, Lisa Glukhovsky, Mary Ann Picone: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Learning, Cognitive fatigue, Multiple sclerosis, Performance (CG17) Accelerometer Protocol Adherence in a Sample of People with Multiple Sclerosis and Cognitive Impairment Janet D. Morrison School of Nursing, The University of Texas at Austin, Austin, TX
Background: Impaired cognitive function affects up to 70% of persons with multiple sclerosis (MS), is regularly underdiagnosed and poorly managed, and has few treatment options. Physical activity has been related to better cognitive performance in both healthy and cognitively impaired older adults. Research scientists have suggested the possibility of a comparable linkage between greater physical activity and better cognitive functioning in persons with MS. Methods used to quantify physical activity in persons with MS, such as wearing an accelerometer during waking hours for 7 days, may be more challenging for a sample of persons with MS and cognitive impairment. Objectives: To determine the feasibility of using accelerometers to characterize physical activity in persons with MS and cognitive impairment enrolled in a study investigating the effects of physical activity on cognitive function. Methods: Persons with MS enrolled in the study scored 600 minutes were considered to have adequately adhered to the protocol. Results: Sample characteristics (n = 14): mean age 41.9 ± 9.8; mean MS duration 11.4 ± 7.5; mean years of education 16.4 ± 2.6 years; mean SDMT raw score 41.9 ± 9.8; 64% female; 79% white; 21% black; 21% Hispanic; 79% relapsing-remitting MS; 7% secondary progressive MS; 14% primary progressive MS; 50% employed full or part time and 29% unemployed due to disability. Eleven of 14 participants (78.6%) had 3 or more days of >600 minutes of accelerometer wear time. Conclusions: A sample of persons with MS and cognitive impairment was able to adhere to a 7-day accelerometer protocol. Improved adherence may be achieved by sending daily text, phone, or email reminders and/or by placing the accelerometer in a conspicuous place overnight (by their cell phone or toothbrush). Supported by: International Organization of MS Nurses, National Institute of Nursing Research at the National Institutes of Health Disclosure: International Organization of MS Nurses, National Institute of Nursing Research at the National Institutes of Health (grant/research support) Keywords: Nursing management in MS, Physical activity (CG18) Stability of Depression in Patients with Multiple Sclerosis Jason Botvinick, Jeffrey G. Portnoy, Gabriel Hoffnung, Lisa Glukhovsky, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Depression in multiple sclerosis (MS) has an estimated lifetime prevalence of 50% and a point-prevalence of 20% to 25%. However, few studies have followed the course of depression in MS longitudinally. Prior research has shown the course of depression to be stable, but these studies have been limited in sample size and longitudinal range. Objectives: To evaluate the stability of depression in MS patients over a period greater than 5 years. Methods: Participants (N = 349) were recruited from an outpatient clinic at a large medical center in New Jersey. Longitudinal data were collected as part of an ongoing research project. Participants completed a Beck Depression Inventory-II (BDI-II) and a demographic questionnaire. Linear regression was used to examine the relationship between time and change in BDI-II score. Linear regression was also used to relate BDI-II scores at baseline and follow-up. Results: Initial BDI-II significantly predicted BDI at follow-up (β = .603, P < .001). Time did not predict a change in BDI-II score (β = –.026, P = .625).
International Journal of MS Care 23
Posters: Cognition, Depression, and Psychosocial Issues Conclusions: Depression is highly stable in the MS population over more than a 5-year span. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jason Botvinick, Jeffrey G. Portnoy, Gabriel Hoffnung, Lisa Glukhovsky: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Comprehensive care and MS, Psychological issues and MS
Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jason Botvinick, Jeffrey G. Portnoy: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Management of activities of daily living in MS, Psychological issues and MS
(CG19) Disability Predicts Longitudinal Depression in People with Multiple Sclerosis
Jeffrey G. Portnoy,1 Jason Botvinick,1 Gabriel Hoffnung,1 Lisa Glukhovsky,1 Frederick W. Foley2
Jason Botvinick, Jeffrey G. Portnoy, Gabriel Hoffnung, Lisa Glukhovsky, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Depression has been shown to be more stable over time in individuals with multiple sclerosis (MS) than in the general population. However, it is unclear what factors account for the stability of depression in people with MS. Prior research has found Expanded Disability Status Scale (EDSS) scores and measures of fatigue to be significant predictors of depression, but patients’ subjective perceptions of their disability have not been examined in this context. Objectives: To evaluate the predictive value of disability data on depression over time. Methods: Participants (N = 121) were recruited from an outpatient clinic at a large medical center in New Jersey. Longitudinal data were collected as part of an ongoing research project. Participants completed a Beck Depression InventoryII (BDI-II), Incapacity Status Scale (ISS), and demographic questionnaire. Linear regressions were used to assess the ISS as a predictor of BDI-II score at baseline and follow-up, and of change in BDI-II over time. Results: ISS scores positively predicted BDI scores at baseline (β = .429, P < .001) and follow-up (β = .380, P < .001) and change in BDI-II score over time (β = .272 , P = .003). Conclusions: Higher levels of disability predict greater depression in individuals with MS, both cross-sectionally and longitudinally. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jason Botvinick, Jeffrey G. Portnoy, Gabriel Hoffnung, Lisa Glukhovsky: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Psychological issues and MS (CG20) Stability of Both Cognitive-Affective and Somatic Symptoms in Multiple Sclerosis Jason Botvinick, Jeffrey G. Portnoy, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Previous research has shown that there is a difference in the stability of neurovegetative, evaluative, and mood symptoms in multiple sclerosis (MS). There are many reasons why mood might be more variable, including differences in coping style and benefit finding. The Beck Depression Inventory–II (BDI-II) measures two different domains of depressive symptoms: somatic and cognitive-affective. There has not been research that has examined the longitudinal course of depression using these domains in the BDIII. Objectives: To evaluate the stability of the domains of somatic and cognitive-affective symptoms of depression in MS. Methods: Participants (N = 349) were recruited from an outpatient clinic at a large medical center in New Jersey. Longitudinal data were collected as part of an ongoing research project. Participants completed a BDIII and demographic questionnaire. Prior research was used to divide total BDI-II scores into somatic and cognitive-affective scores. Linear regression was used to examine the relationship between time and change in somatic and cognitive-affective BDI-II scores. Linear regression was also used to relate somatic and cognitive-affective BDI-II scores at baseline and follow-up. Results: Time did not significantly predict change in either cognitive-affective (β = –.027, P = .613) or somatic scores (β = .018, P = .735). Initial cognitive-affective scores predicted cognitive-affective scores at follow-up (β = .604, P < .001). Initial somatic scores predicted somatic scores at follow-up (β = .533, P < .001). Conclusions: Depression appears stable across both somatic and cognitive-affective domains over time.
(CG21) Longitudinal Efficacy of Antidepressant Pharmacotherapy in Multiple Sclerosis Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY; 2Holy Name Medical Center, Teaneck, NJ 1
Background: Depressive disorders are highly prevalent comorbidities of multiple sclerosis (MS), and research has suggested that depression among MS patients remains stable over time. Despite the known risks of polypharmacy, little research has investigated the long-term benefits of antidepressant medication on the course of depression in MS. Objectives: To evaluate the longitudinal efficacy of antidepressant medication in MS patients. Methods: Participants (N = 349) were recruited from an outpatient MS clinic at a medical center in New Jersey. Longitudinal depression and medication data were collected as part of ongoing neuropsychological research. Medication information was obtained from participants through interview and medical records, while participants also completed the Beck Depression Inventory-II (BDI). Pearson chi-square test and linear regressions were used to examine the course of depression over time for participants in antidepressant-medicated and nonmedicated groups. Results: Outcome data ranged longitudinally from 0.92 to 71.33 months (mean = 29.50, SD = 17.44). Antidepressant medication status did not significantly relate to clinically meaningful change in BDI score (χ2 = 2.619, P = .270). Time did not significantly predict change in BDI score for the antidepressant (β = −.050, P = .535) or nonantidepressant groups (β = −.006, P = .933). Conclusions: Depression’s stability in the MS population appears refractory to the effects of standard antidepressant pharmacotherapy longitudinally. Additional or alternate management of depressive disorders is indicated for patients with MS. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jeffrey G. Portnoy, Jason Botvinick, Gabriel Hoffnung, Lisa Glukhovsky: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Comprehensive care and MS, MS and the caregiver/family, Psychological issues and MS (CG22) Patient Perceptions of Mood, Cognition, and Fatigue: Lessons from the Incapacity Status Scale Jeffrey G. Portnoy, Marnina B. Stimmel, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: The Incapacity Status Scale (ISS) is a well-validated 16-item interview measuring living disability in multiple sclerosis (MS). However, like many subjective rating scales, it possesses shortcomings in assessing the multiple dimensions of patients’ complaints. In particular, subjective measurement items regarding mood, cognition, and fatigue in MS are often limited in their ability to capture the complexity of the features associated with disability in these areas. Objectives: To assess the ability of the mood, cognition, and fatigability items of the ISS to accurately represent these constructs. Methods: Retrospective chart review of patients who had undergone neuropsychological testing (N = 68) was performed at an outpatient MS clinic in a large medical center. Data collected included the ISS, the Behavior Rating Inventory of Executive Function (BRIEF), three mood inventories, six neuropsychological tests of cognition, and two fatigue inventories. Internal consistency analyses of the ISS and partial Spearman rank-order correlations, controlled for the effects of age, race, and gender, were conducted to examine the relationships among ISS mood, cognition, and fatigability items and external measures of those three constructs. Results: Two ISS questions were excluded from internal consistency analysis due to high nonresponse rates: medical problems (86.8%) and sexual function (64.5%). Internal consistency for the ISS was strong (Cronbach α = .883).
International Journal of MS Care 24
Posters: Cognition, Depression, and Psychosocial Issues ISS mood was significantly correlated with the BRIEF (ρ = .300, P = .045) and three other inventories (ρ = .301, P = .032; ρ = .358, P = .009; ρ = .392, P = .001). ISS fatigue was significantly correlated with both fatigue inventories (ρ = .309, P = .029; ρ = .424, P = .008). ISS cognition was significantly correlated with only one of six cognitive tests (ρ = −.347, P = .008). Conclusions: The ISS items on mood and fatigability appear to be valid construct measures. The cognition item fails to capture almost all dimensions of cognitive dysfunction in MS. Implications for the development and application of future subjective MS rating instruments are discussed. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jeffrey G. Portnoy, Marnina B. Stimmel: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Management of activities of daily living in MS, MS and the caregiver/family, Psychological issues and MS (CG23) Subjective and Objective Impairment Metrics as Unique Correlates of Employment Status in Multiple Sclerosis Jeffrey G. Portnoy, Eliana Pasternak, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Disability in multiple sclerosis (MS) is multifaceted, with physical, cognitive, and psychosocial elements all playing roles in overall disease burden. Given the high rates of unemployment associated with MS, examination of the potential relationship between employment and measures of impairment across multiple domains could provide valuable insight into the factors underlying unemployment among individuals with MS. Objectives: Determine peripheral measures associated with employment status in MS. Methods: Retrospective chart review was performed for patients who had undergone neuropsychological testing (N = 61) at a medical center’s outpatient MS clinic. Partial Spearman rank-order correlations, controlled for the effects of age, race, and gender, assessed the relationships between employment status and objective and subjective neuropsychological tests and inventories. Results: Employment status was significantly associated with a subjective inventory of neuropsychological impairment (ρ = −.414, P = .006) and objective neurocognitive tests of visual memory (ρ = .299, P = .017), attention and processing speed (ρ = .387, P = .003), and verbal fluency (ρ = .274, P = .030; ρ = .347, P = .009). Conclusions: Domains of cognitive functioning, rated both subjectively and objectively, are strongly related to MS patients’ employment status. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jeffrey G. Portnoy, Eliana Pasternak: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Employment in MS, Management of activities of daily living in MS, Psychological issues and MS (CG24) Timed Oral Cognitive Tests Predict Brainstem Dysfunction Complaints Jeffrey G. Portnoy, Marnina B. Stimmel, Roseann Archetti, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Many neuropsychological tests have been validated for the assessment of cognitive function in multiple sclerosis (MS). While these tests are typically used to evaluate the underlying features of complex cognition, such as processing speed, attention, and language, the demands they place on speeded brainstem activity may give them additional clinical value as potential predictors of complaints related to brainstem dysfunction, such as dysarthria and dysphagia. Furthermore, these tests may be less appropriate measures for patients whose performance is rate-limited by difficulties with speech production. Objectives: Examine the relationship between timed oral tests of cognition and complaints associated with brainstem dysfunction. Methods: Patients who had undergone neuropsychological testing (N = 66) were examined via retrospective chart review. Patients completed orally administered neurocognitive measures as part of a neuropsychological battery. Kendall τ correlations were computed to examine the relationship between the neurocognitive measures and Incapacity Status Scale items on feeding and
speech/hearing. Ordinal regressions examined predictive models of these disability items using three neurocognitive measures: the Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Stroop Color and Word Test. Results: Significant correlations were noted between at least one brainstem disability item and six neuropsychological tests. Models using the SDMT, COWAT, and Stroop significantly predicted scores on both feeding (R2 = .438, P = .001) and speech/hearing items (R2 = .335, P = .001). Conclusions: A strong predictive relationship exists between timed oral cognitive tests and subjective complaints of brainstem dysfunction. In patients with impaired production of speech, such tests may be skewed measures of cognitive function; however, such tests could possess previously unseen value as objective measurements of disordered brainstem activity. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Jeffrey G. Portnoy, Marnina B. Stimmel, Roseann Archetti: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Management of activities of daily living in MS, Psychological issues and MS (CG25) Relationship of Changes in Physical Activity to Fatigue and Depression in Pediatric Multiple Sclerosis Joshua D. Lee, Stephanie A. Grover, E. Ann Yeh Departments of Neurology and Neurosciences and Mental Health, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Background: Fatigue and depression are common symptoms of pediatric multiple sclerosis (MS). Whether modifiable behaviors, such as physical activity, influence fatigue and depression in this patient population is unclear. Objectives: We evaluated the relationship between changes in physical activity and the evolution of fatigue and depression over time in pediatric patients with MS and monophasic acquired demyelinating syndromes (mono-ADS). Methods: Physical activity, fatigue, and depression were assessed at baseline and 6–12 months later using standardized questionnaires in consecutive children (age 5.8–17.7 years) with MS (n = 27) and mono-ADS (n = 29) attending a pediatric MS clinic in Toronto, Canada. Questionnaires queried physical activity (Godin Leisure Time Exercise Questionnaire), fatigue (Varni PedsQL), and depression (CES-DC). Changes in physical activity, fatigue, and depression over time and their interactions were compared within and between MS and monoADS cohorts using Fisher exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and Spearman correlation analysis. This study was approved by the institutional research ethics committee. Results: MS patients reported lower total physical activity at baseline (40.0 [39.0] vs. 63.0 [44.0] metabolic equivalents [METs], P = .02) and at follow-up (40.0 [41.5] vs. 56.0 [50.5] METs, P = .10), as well as less strenuous physical activity at baseline (18.0 [31.5] vs. 27.0 [36.0] METs, P = .09) and follow-up (9.0 [27.0] vs. 27.0 [33.8] METs, P = .04) compared to mono-ADS. MS patients reported higher fatigue scores (general fatigue: 7.0 [7.0] vs. 5.0 [7.5], P = 0.07; total fatigue: 25.0 [16.0] vs. 16.0 [21.0], P = .08) than mono-ADS patients at follow-up. MS patients also reported higher depression scores at baseline (15.0 [12.0] vs. 9.0 [7.0], P = .04) and follow-up (15.0 [19.0] vs. 6.0 [10.0], P = .001). Furthermore, MS patients exhibited a trend toward worsening depression (+2.0 [7.0], P = .09) compared to a trend toward improvement in mono-ADS patients (–3.0 [7.5], P = .11). In the MS cohort, decreased total physical activity correlated with greater fatigue at follow-up (ρ = –0.5 to –0.4, P < .05). Similarly, decreased strenuous physical activity and HCS correlated with greater fatigue (ρ = –0.6 to –0.4, P < .05) and depression (ρ = –0.4, P < .05) at follow-up. Conclusions: Decrease in physical activity is associated with greater fatigue and depression in pediatric MS patients. Limitations of this study include small sample size and observational design precluding inferences of causality. Future interventional studies may clarify the relationship of physical activity to fatigue and depression in this population. Supported by: SickKids Foundation, SickKids Research Institute Disclosure: Nothing to disclose Keywords: Comprehensive care and MS, Psychological issues and MS
International Journal of MS Care 25
Posters: Cognition, Depression, and Psychosocial Issues (CG26) The Feasibility of a Positive Psychology Group Intervention for Patients with Multiple Sclerosis Kaitlynne Leclaire,1 Bonnie I. Glanz,2 Allison LaRussa,1 Fiona Stuart,1 Brian C. Healy,1 Jeff Huffman,3 Tanuja Chitnis,4 Howard L. Weiner,1 Audrey H. Cecil5 Neurology, Brigham and Women’s Hospital, Brookline, MA; 2Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, Brookline, MA; 3Massachusetts General Hospital, Boston, MA; 4Massachusetts General Hospital for Children, Boston, MA; 5Social Work, Brigham and Women’s Hospital, Brookline, MA 1
Background: Positive psychology (PP) uses targeted activities to increase the frequency and intensity of positive emotional experiences such as optimism. This intervention has successfully improved several patient-reported outcomes (PROs) in healthy subjects as well as subjects with cardiovascular and other diseases, but it has not been used in multiple sclerosis (MS). Objectives: To evaluate the feasibility and tolerability of a 5-week group PP training intervention and determine the impact of the intervention on optimism and positive affect in patients with MS. Methods: Participants (n = 11) were recruited from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital, Partners MS Center (CLIMB). All participants were female, and their ages ranged from 36 to 62 years (mean = 53). Subjects completed 5 weeks of group PP training in groups of 3 to 5. The PP activities included: gratitude for positive events, personal strengths, a gratitude letter, enjoyable and meaningful activities, and remembering past successes. Participants completed the exercises in between sessions, and the groups met once per week to discuss the exercises, with sessions lasting from 45 to 60 minutes. The primary outcome of the study was the proportion of subjects who completed the 5 weeks in order to measure feasibility and tolerability of the intervention. In addition, participants completed a battery of PROs pre and post intervention. The battery consisted of measures of optimism (LOT-R), positive and negative affect (PANAS), anxiety (STAI), depression (CES-D), and quality of life (SF-36). The change in the scores for each PRO was assessed using a paired t test. Results: All participants completed the intervention (proportion completed = 1; 95% CI: 0.72-1), demonstrating the feasibility and tolerability of the intervention. For each PRO, the mean change showed a positive effect of the intervention. In particular, optimism, positive affect, and quality of life were all observed to increase, while negative affect, depression, and anxiety were all observed to decrease. Despite the constancy of the direction, only changes on the vitality subscale of the SF-36 (P = .012) and the CES-D (P = .049) were statistically significant. Conclusions: Our study demonstrates that group PP is a feasible intervention that should be studied further in larger numbers of MS subjects. Supported by: Merck Serono Disclosure: Kaitlynne Leclaire, Allison LaRussa, Fiona Stuart: Google Life Sciences, Merck Serono (grant/research support). Bonnie I. Glanz: Google Life Sciences, Merck Serono, National Multiple Sclerosis Society (grant/research support). Brian C. Healy: Biogen Idec (consulting fees); Genzyme, Google Life Sciences, Merck Serono, Novartis (grant/research support). Jeff Huffman, Tanuja Chitnis, Howard L. Weiner, Audrey H. Cecil: Nothing to disclose. Keywords: Psychological issues and MS (CG27) Is It Depression? Atypical Presentation of Mood Disorders in Multiple Sclerosis Laura T. Safar Psychiatry, Harvard Medical School, Boston, MA
Background: The clinical presentation of psychiatric disorders in the setting of neurologic illnesses may differ from the classic presentation of primary psychiatric disorders. Patients with multiple sclerosis (MS) and depression may present an increased prevalence of irritability, cognitive disturbances, and other symptoms compared to patients with major depressive disorder and no neurologic illness. In addition, nondepressed patients with MS frequently present symptoms of fatigue and cognitive and sleep disturbances that may mimic depression. These factors may misguide clinicians and cause patients to receive an inadequate diagnosis and treatment. Objectives: To examine the frequency of fatigue, sleep disturbances, subjective cognitive complaints, irritability, impulsivity, and affect disturbances
in patients with MS referred to a psychiatric evaluation and their relationship with these patients’ psychiatric diagnoses. Methods: 50 patients with MS referred to psychiatric evaluation were examined on the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item scale (GAD-7), the Center for Neurologic Study-Lability Scale (CNS-LS) for pseudobulbar affect, the Mood Disorder Questionnaire (MDQ), and the Modified Fatigue Impact Scale (MFIS). Results: Symptoms of fatigue, sleep disturbances, and subjective cognitive complaints were highly prevalent in these patients, both in cases clinically assessed as presenting a depressive syndrome and in those without this diagnosis. A subset of patients presented a high PHQ-9 score, but did not present clinical depression. A significant proportion of patients reported isolated symptoms of bipolar disorder and pseudobulbar affect without meeting clinical criteria for these two entities. Conclusions: The clinical presentation of psychiatric disorders in MS may differ from that of primary psychiatric disorders. Screening tools and formal assessment instruments may be helpful to identify the presence of symptoms in a systematic way, but clinical correlation is needed to reach an accurate diagnosis and for the adequate management of these patients. Supported by: None Disclosure: Nothing to disclose Keywords: Comprehensive care and MS, Psychological issues and MS (CG28) Motor and Cognitive Predictors of Fall Risk in Multiple Sclerosis Lisa Glukhovsky, Gabriel Hoffnung, Jason Botvinick, Jeffrey G. Portnoy, Marnina B. Stimmel, Roee Holtzer, Frederick W. Foley Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY
Background: Persons with multiple sclerosis (PwMS) carry a higher risk of falls; studies estimate that at least 50% of PwMS may experience a fall over a 3- to 6-month period. As PwMS may manifest varying physical and neuropsychological symptoms with complex interactions, it is important to elucidate the relationship of these symptoms to fall risk. Objectives: The study aimed to examine motor and cognitive predictors of fall risk. Methods: Data were collected from 30 participants at a large outpatient medical center in New Jersey. All participants signed informed consent forms and were diagnosed previously with MS. Participants were administered the Nine-Hole Peg Test (NHPT), Timed 25-Foot Walk (T25FW), Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS), and Expanded Disability Status Scale (EDSS). Participants were also asked to provide demographic information and history of falls during the previous 2 months. Bivariate correlations were conducted to select covariate variables for logistic regressions. Binary logistic regressions were conducted to examine whether motor and cognitive symptoms each predict fall risk. Age, gender, disability level (EDSS), and verbal learning/memory (California Verbal Learning Test-Second Edition [CVLT-II] Total Immediate Recall) were entered into the first block of the regressions because prior studies have found these variables to be associated with mobility. Results: Upper-extremity function (NHPT) and processing speed (SDMT Total) were found to correlate significantly with whether participants had fallen during the previous 2 months. After controlling for age, gender, disability level, verbal learning/memory, and walking speed, dominant upper-extremity function significantly predicted number of falls (B = .204, P = .029). In a second regression controlling for age, gender, disability level, and verbal learning/memory, processing speed significantly predicted number of falls (B = –1.285, P = .035). Conclusions: Reduced performance in dominant upper motor function and processing speed each predicted higher number of falls in PwMS. This research provides potentially valuable information about identification and reduction of fall risk for MS. Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Lisa Glukhovsky, Gabriel Hoffnung, Jason Botvinick, Jeffrey G. Portnoy, Marnina B. Stimmel, Roee Holtzer: Nothing to disclose. Frederick W. Foley: Biogen Idec, Bayer HealthCare Pharmaceuticals (consulting fees). Keywords: Neuropsychology and MS, Psychological issues and MS
International Journal of MS Care 26
Posters: Cognition, Depression, and Psychosocial Issues (CG29) TeriMOOD Study Design: Assessing Changes in Depressed Mood in Patients with Relapsing Multiple Sclerosis Switching from Interferon Beta to Teriflunomide Due to Symptoms of Depression Lori Hendin Travis,1 Jeffrey Chavin,2 Maria Melanson,2 Adel Gehchan,3 Matt Mandel2 Phoenix Neurological Associates Ltd, Phoenix, AZ; 2Genzyme, a Sanofi company, Cambridge, MA; 3Genzyme Canada, Mississauga, ON, Canada 1
Background: Teriflunomide is an immunomodulatory agent approved for the treatment of relapsing forms of multiple sclerosis (RMS). Depression is a common symptom in patients with MS, with lifetime prevalence estimates as high as 50%. Depression is a result of both neuropathology (eg, brain lesions) and psychosocial factors (eg, coping style, social support system). There is also evidence that some MS treatments, such as interferon beta (IFNβ), may exacerbate depression. It is important to address depression in patients with MS, as this comorbidity can lead to reduced health-related quality of life (QOL), reduced adherence to therapy, and increased morbidity and mortality. Objectives: To describe the design of the TeriMOOD study, which evaluates changes in depressed mood in patients with RMS switching from IFNβ therapy to teriflunomide due to symptoms of depression. Methods: TeriMOOD is a prospective, multicenter, single-arm observational study being initiated in the United States and Canada. Inclusion criteria: age 18–65 years (inclusive), a diagnosis of RMS, switching from any IFNβ therapy (prior duration of treatment ≥6 months) to teriflunomide 14 mg due to symptoms of depression, and a screening Beck Depression Inventory-II (BDI-II) score ≥14. Target recruitment is 75 patients. The primary endpoint is the assessment of changes in depressed mood over 6 months, as measured by BDI-II. Secondary endpoints include the proportion of patients who remain free of relapse after 6 months, changes in health-related QOL (measured using the Multiple Sclerosis International Quality of Life [MusiQOL] scale), and cognitive function (measured using the Symbol Digit Modalities Test [SDMT]). The tertiary endpoint is change in antidepressant use. Adverse events are monitored throughout the study. Results: BDI-II, MusiQOL, and SDMT assessments used in TeriMOOD will be discussed in more detail in the presentation. Patient results from TeriMOOD will be reported after study completion. Conclusions: TeriMOOD will evaluate the impact on QOL and cognitive function when switching treatment from IFNβ to teriflunomide due to the presence of depressed mood. Understanding depressive mood changes and their impact on QOL is an important area of research, particularly given the recent trend to prioritize wellness and emotional well-being in treatment goals for patients with MS. Supported by: Genzyme, a Sanofi company Disclosure: Lori Hendin Travis: Acorda, Biogen Idec, EMD Serono, Genzyme, Novartis, Pfizer, Mallinckrodt (consulting fees); Biogen, EMD Serono, Genzyme (grant/research support). Jeffrey Chavin, Maria Melanson, Adel Gehchan: Genzyme, a Sanofi company (employee). Matt Mandel: Genzyme, a Sanofi company (employee, ownership interest). Keywords: Disease-modifying treatments in MS, Management of activities of daily living in MS, Psychological issues and MS (CG30) Longitudinal Evaluation of Cognition in Multiple Sclerosis: Impact of Cognitive Reserve Louise M. Gresham,1 Roxana M. Barbu,2 Jason A. Berard,3 Lisa A.S. Walker4 Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 2Institute of Cognitive Science, Carleton University, Ottawa, ON, Canada; 3Psychology, University of Ottawa, Ottawa, ON, Canada; 4Psychology, The Ottawa Hospital, Ottawa, ON, Canada 1
Background: Up to 70% of people with multiple sclerosis (PwMS) suffer cognitive impairment in multiple domains, including complex attention, information processing speed, learning and memory, and executive function. Cognitive outcomes in PwMS, however, are highly variable. For instance, some PwMS remain cognitively intact despite advanced disease. Cognitive reserve (CR) theory postulates that individuals with higher levels of intellectual enrichment can tolerate more pathology than others before exhibiting cognitive impairment. The North American Adult Reading Test (NAART), which measures a person’s ability to pronounce phonetically irregular words, estimates
the verbal intellectual abilities of individuals who have acquired cognitive dysfunction. CR can be quantified using NAART and years of education as proxy measures. Objectives: The current study evaluated whether or not PwMS were impaired compared to healthy controls (HC) on measures of cognitive functioning across several domains. This study also investigated whether CR predicted cognitive outcome following a 3-year interval. Methods: Thirty-two individuals with early-phase relapsing-remitting MS were recruited from the MS clinic of the Ottawa Hospital. All had a mild level of physical disability and a disease duration of less than 10 years. In addition, 32 age-, education-, and IQ-matched healthy controls were recruited from the community. At baseline and after a 3-year interval, participants completed an extensive battery of neuropsychological tests that evaluated a variety of cognitive domains (eg, information processing speed, visual/verbal memory). CR was assessed using individuals’ education (in years), and their score on the NAART. Results: On tasks targeting information processing speed, memory, and executive functions, PwMS did worse than HC. On memory and language tasks there was no significant difference between PwMS and HC. CR measures, specifically years of education and NAART scores, did not predict follow-up scores in any cognitive domain. Conclusions: These results suggest that PwMS show less cognitive impairment in some cognitive domains compared to others in the early phase of the disease. Second, results indicate that CR did not predict cognitive outcome in the early phase of the disease in this sample. Results were discussed in terms of unique characteristics of our sample. Supported by: Multiple Sclerosis Society of Canada Disclosure: Nothing to disclose Keywords: Psychological issues and MS (CG31) Relationship Between Body Mass Index, Depression, and Ambulation in a Multiple Sclerosis Population Lucille J. Carriere,1 Amy B. Sullivan,2 Lael A. Stone2 Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Murfreesboro, TN; Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 1 2
Background: Obesity has become a national epidemic within the United States. However, less attention has focused on the relationship between obesity and disability due to multiple sclerosis (MS). Evidence suggests that obesity, a pro-inflammatory state, may exacerbate neurologic diseases and may have implications for depression, quality of life (QOL), and ambulation. Data suggest that depression and QOL are significantly worse in overweight/obese MS patients. Evidence is mixed with regard to weight and ambulation, but higher body-mass index (BMI) has been associated with accelerated disability in MS.5 Less is known about the relationship between ambulation and depression, but a recent study found depression to be predictive of walking impairment over time. Objectives: To expand current knowledge regarding the relationship between BMI, mood, QOL, and ambulation in an MS population. Methods: Data collected retrospectively from a large clinical database at the Cleveland Clinic. Inclusion criteria: new/follow-up neurology visit at the Mellen Center during a 6-month period, >18 years of age, MS diagnosis, BMI data for visit, and ambulatory. Height/weight data collected exclusively by medical staff. Ambulation was measured by the Timed 25-Foot Walk (T25FW), QOL by the EuroQOL (EQ-5D), and depression by the Patient Health Questionnaire-9 (PHQ-9). Results: Nearly 67% of the study sample (N = 2256) was classified as overweight/obese. Separate multivariate linear regression models were run for T25FW, BMI, and PHQ-9. For the T25FW model, BMI and depression were significant predictors of walking speed. Patients experienced a slower walking speed with a higher BMI as well as with higher levels of depressive symptoms. For the depression model, increased BMI was significantly associated with an increased PHQ-9 total score. For the QOL model, increased BMI was significantly associated with a decreased EQ-5D index score. Conclusions: Overall, higher body mass was associated with decreased walking speed, increased symptoms of depression, and lower QOL. Findings suggest that obesity is associated with significant adverse outcomes for emotional/
International Journal of MS Care 27
Posters: Cognition, Depression, and Psychosocial Issues physical functioning in an MS cohort. Clinically, results suggest a need for weight loss programs to target patients with higher BMI to possibly preserve or improve ambulation. The relationship between depression and decreased ambulation highlights the importance of ongoing depression screening at neurology visits and appropriate referrals to behavioral medicine. Walking impairments have been identified as particularly damaging to QOL; thus, a comprehensive approach to managing depression may have far-reaching benefits for overall health of MS patients. Future studies should utilize longitudinal designs, as well as examine the role of comorbidities as they relate to obesity in MS; such understanding may provide clinical utility for providers and possibly improve long-term emotional/physical functioning of individuals with MS. Supported by: None Disclosure: Lucille J. Carriere, Lael A. Stone: Nothing to disclose. Amy B. Sullivan: National Multiple Sclerosis Society, Novartis (consulting fees). Keywords: Obesity, Psychological issues and MS (CG32) Validity and Reliability of the Auditory Consonant Trigrams Test in Multiple Sclerosis Maha Abu-AlHawa,1 Jason A. Berard,2 Leila Osman,3 Louise M. Gresham,4 Lisa A.S. Walker5 Institute of Cognitive Science, Carleton University, Ottawa, ON, Canada; 2Psychology, University of Ottawa, Ottawa, ON, Canada; 3Ottawa Hospital Research Institute, Ottawa, ON, Canada; 4Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 5 Psychology, The Ottawa Hospital, Ottawa, ON, Canada 1
Background: It is well established that cognitive impairment is present in over half of people with multiple sclerosis (PwMS). While evaluation through neuropsychological assessment is optimal, access to such services is limited. Thus, there is an increased need for assessment tools that can be administered by non-neuropsychologists in the clinic setting. The Brief International Cognitive Assessment for MS (BICAMS) was established for just such a purpose. However, the BICAMS fails to evaluate working memory. The Auditory Consonant Trigrams test (ACT) is a measure of working memory under conditions of interference that takes approximately 5 minutes to administer. The utility of ACT in MS has yet to be fully established. Objectives: The goal of the present study was to determine if ACT can discriminate between PwMS and healthy controls (HC) and to establish its psychometric properties. Methods: Fifty-seven PwMS recruited from the Ottawa Hospital MS Clinic were matched to 51 HC on age, sex, and education. Participants completed the ACT (9-s and 18-s delay intervals) at baseline and 2-week follow-up as part of a larger battery of tests that also included the BICAMS. Results: PwMS performed significantly worse than HC on the ACT (9 and 18 s) at both baseline and follow-up. On the 9-s ACT 35.1% were classified as impaired (1.5 SD below HC mean) at both baseline and follow-up. On the 18-s ACT 17.5% and 29.8% were classified as impaired at baseline and follow-up, respectively. The sensitivity of the ACT is comparable to that of the individual BICAMS measures. Testretest reliability of both the 9-s (r = 0.52, P 5 at baseline; as expected, these patients had higher EDSS scores, a shorter time since first MS diagnosis, and a greater occurrence of progressive MS compared with those with MSSS scores ≤5. Consistent with effects of teriflunomide in the overall study population, ARR was significantly reduced by both doses of teriflunomide in the MSSS >5 subgroup (relative reductions: 30.3%, P = .0002 and 37.5%, P < .0001, for teriflunomide 7 mg and 14 mg vs. placebo, respectively). Similarly, teriflunomide 14 mg also significantly reduced the risk of both 12-week (HR reduction [HRR]: 40.3%; P = .0082) and 24-week confirmed disability progression (HRR: 46.1%; P = .0108) in this population. Conclusions: Teriflunomide was associated with significant reductions in ARR and disability progression in patients from the pooled TEMSO/TOWER studies with faster-advancing disease, as represented by baseline MSSS scores >5. Together with evidence of efficacy in patients with a first clinical episode suggestive of MS from the TOPIC study (NCT00622700), teriflunomide is efficacious across a broad spectrum of MS disease severity. Supported by: Genzyme, a Sanofi company Disclosure: Aaron E. Miller: Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech, Genzyme, GSK, Mallinckrodt Pharmaceuticals (Questcor), Novartis, Roche, Teva (consulting fees); Biogen Idec,
International Journal of MS Care 33
Posters: Disease Modification Genentech, Novartis, Questcor, Roche, Sanofi (grant/research support). Ludwig Kappos: Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation (grant/research support); Neurostatus Systems GmbH (royalty); Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva (speaker fees); Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, XenoPort (steering committee, advisory board, and consultancy fees); Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva (consulting fees). Jiwon Oh: Biogen, EMD Serono, Genzyme, Novartis, Roche, Teva (consulting fees); MS Society of Canada, Biogen, Genzyme (grant/research support). Karthinathan Thangavelu: Genzyme (employee). Pascal Rufi: Sanofi (employee). Steve Cavalier, Philippe Truffinet: Genzyme (employee, ownership interest). Giancarlo Comi: Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation (SSIF), Teva (fees for non-CME services from commercial interests or their agents); Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation (SSIF), Teva (consulting fees). Keywords: Disease-modifying treatments in MS, Imaging and MS, Natural history of MS (DX11) Effects of Induced Depression on the Animal Model of Multiple Sclerosis: An Overlooked Disability Amal Fuad Almahroos, Zahra Almosawi, Hawra Alalwan, Reem Abdulla, Fajer Alammadi, Ahmed Al-Mahrezi, Ahmmed Almubarak, Ayman Mohamed, Amer Kamal College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
Background: Depression is a common disabling symptom of multiple sclerosis (MS) with a lifetime prevalence of 50%. Objectives: The aim of this study is to investigate the impact of induced depression on a cuprizone mouse model of demyelination. Methods: Mice were divided into cuprizone with no intervention (Cup-O), cuprizone undergoing induced depression (Cup-Dep), and control groups (9–10 per group). Depression was induced by repeated open-space forced swim and was implemented 6 days prior to the testing period. Multiple sclerosis was induced by continuously feeding 6-week-old C57BL/6 male mice a 0.2% cuprizone-enriched diet. Spatial learning and memory were tested using Morris water maze while rotarod was used to assess motor function. Results: Cognitive and motor deficits were established in a cuprizone mouse model of demyelination as Cup-O had worse results than the control group in Morris water maze (P < .001) and rotarod (P < .05). Induced depression was seen to exaggerate the aforementioned deficits; Cup-Dep showed a significantly reduced performance in Morris water maze (P < .001) and rotarod (P < .05) in comparison to Cup-O. Conclusions: Depression can further worsen the natural disease course of an MS model. Therefore, depression-ameliorating measures should be considered as a part of an MS management plan based on the results of this study. Supported by: None Disclosure: Nothing to disclose Keywords: Depression (DX12) Effect of Ocrelizumab on Humoral Immunity Markers in the Phase 3, Double-Blind, Double-Dummy, Interferon Beta-1a–Controlled OPERA I and OPERA II Studies Amit Bar-Or,1 Douglas L. Arnold,1,2 Giancarlo Comi,3 Hans-Peter Hartung,4 Stephen L. Hauser,5 Fred Lublin,6 Krzysztof Selmaj,7 Anthony Traboulsee,8 Peter Chin,9 Paulo Fontoura,10 Hideki Garren,10 Gaelle Klingelschmitt,10 Donna Masterman,9 Ludwig Kappos,11 on behalf of the OPERA I and OPERA II investigators McGill University, Montreal, QC, Canada; 2NeuroRx Research, Montreal, QC, Canada; University Vita-Salute San Raffaele, Milan, Italy; 4Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 5University of California, San Francisco, CA; 6Icahn School of Medicine at Mount Sinai, New York, NY; 7Medical University of Lodz, Lodz, Poland; 8 University of British Columbia, Vancouver, BC, Canada; 9Genentech, Inc, South San Francisco, CA; 10F. Hoffmann-La Roche Ltd, Basel, Switzerland; 11University Hospital Basel, Basel, Switzerland 1 3
Background: Ocrelizumab (OCR) is a humanized monoclonal antibody that targets CD20+ B cells. Selective depletion of CD20+ B cells may potentially preserve the capacity for B-cell reconstitution and preexisting humoral immunity. Objectives: To assess the
effect of OCR on specific humoral immunity in two identical phase 3, randomized, double-blind, double-dummy, interferon beta-1a (IFNβ-1a)–controlled trials in relapsing multiple sclerosis (OPERA I and OPERA II). Methods: In OPERA I and OPERA II, patients were randomized 1:1 to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFNβ-1a 44 μg 3 times weekly over the 96-week study treatment period. Prior to study enrollment, physicians were advised to review patient immunization status and follow local guidance for vaccination; immunizations were to be completed ≥6 weeks prior to treatment. Measurements of antibody (Ab) titers against mumps, rubella, varicella, and Streptococcus pneumoniae were taken at baseline and at weeks 12, 24, 48, 72, and 96. The proportion of patients with Ab levels that could be considered protective was assessed for each treatment group over time. Results: The pooled safety analysis of the OPERA I and OPERA II studies included 826 IFNβ-1a–treated and 825 OCR-treated patients. At baseline, 94.1% and 93.6% of the IFNβ-1a and OCR groups, respectively, had positive levels of mumps Ab; this proportion ranged (min–max) 92.7–94.8% and 91.8–93.5% over the 6 measurements taken during the 96-week study treatment period. Positive rubella Ab levels were seen among 87.9% and 89.0% of the IFNβ-1a and OCR groups, respectively, at baseline and ranged 89.8–90.8% and 88.7–89.4% over the treatment period. Positive varicella Ab levels were seen in 95.5% of both treatment groups at baseline and ranged 96.2–97.5% and 94.8–95.6% over the treatment period in the IFNβ1a and OCR groups, respectively. Among the evaluable patients, the mean (SD) level of S. pneumoniae Ab was 53.67 (54.13) mg/L and 55.35 (67.00) mg/L at baseline; at 96 weeks, the mean change from baseline was −1.13 (40.25) mg/L and −1.99 (59.60) mg/L in the IFNβ-1a and OCR groups, respectively. Conclusions: In OPERA I and OPERA II, Ab titers against common viral and bacterial antigens were similar between the IFNβ-1a and OCR groups at baseline and were maintained during the 96-week study treatment period. Treatment with OCR does not appear to affect preexisting humoral immunity. Funded by: F. Hoffmann-La Roche Ltd Disclosure: Amit Bar-Or: F. Hoffmann-La Roche Ltd, Genentech, Biogen Idec, GlaxoSmithKline, Merck/EMD Serono, MedImmune, Mitsubishi Pharma, Ono Pharma, Receptos, Sanofi-Genzyme, Guthy-Jackson/GGF, Novartis (grant/ research support, served on scientific advisory boards). Douglas L. Arnold: NeuroRx Research, Acorda Therapeutics, Biogen, Genzyme, F. Hoffmann-La Roche Ltd, Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi, Teva (consulting fees, equity interest). Giancarlo Comi: Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Bayer, Excemed, Serono Symposia International Foundation, Almirall, Chugai, Receptos (consulting services and speaking activities). Hans-Peter Hartung: Biogen, F. Hoffmann-La Roche Ltd, GeNeuro, Genzyme, Merck Serono, Novartis, Octapharma, Opexa, Receptos, Sanofi, Teva with approval by the Rector of Heinrich-Heine-University (consulting, serving on steering committees and ad boards, and speaking at scientific symposia). Stephen L. Hauser: Annexon, Symbiotix, Bionure, F. Hoffmann-La Roche Ltd (serves on scientific advisory boards; received travel reimbursement and writing assistance). Fred Lublin: F. Hoffmann-La Roche Ltd, Genentech, Inc, Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB Technologies, Akros, Cognition Pharmaceuticals, Inc (advisory boards, drug safety monitoring board, co-chief editor for journal Multiple Sclerosis and Related Diseases); Novartis Pharmaceuticals Corp, Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS, Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt (advisory boards, drug safety monitoring board, co-chief editor for journal Multiple Sclerosis and Related Diseases, consulting fees, grant/research support, ownership interest). Krzysztof Selmaj: Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd, Merck, Synthon, Receptos, Genzyme (honoraria for advisory boards). Anthony Traboulsee: Biogen, F. Hoffman-La Roche Ltd, Genzyme, Serono, Teva, Chugai, Canadian Institute for Health Research, Michael Smith Foundation, MS Society of Canada (grant/research support, speaker fees and/or advisory board fees). Peter Chin, Donna Masterman: Genentech, Inc (employee, ownership interest). Paulo Fontoura, Hideki Garren, Gaelle Klingelschmitt: F. Hoffmann-La Roche Ltd (employee, ownership interest). Ludwig Kappos: Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, UCB, Xenoport, Teva, CSL Behring, Neurostatus Systems AG (grant/research support, royalty, steering committee, advisory board, consultancy fees, speaker fees, support of educational activi-
International Journal of MS Care 34
Posters: Disease Modification ties); F. Hoffmann-La Roche Ltd, Swiss Multiple Sclerosis Society, Swiss National Research Foundation, European Union, Roche Research Foundations (steering committee, advisory board, consultancy fees, speaker fees, support of educational activities). Keywords: Disease-modifying treatments in MS, Immunology and MS (DX13) Real-World Outpatient Resource Use of Patients with Multiple Sclerosis Newly Initiating Subcutaneous Interferon Beta-1a Versus Oral Disease-Modifying Drugs Chris M. Kozma,1 Frederick Munschauer,2 Amy L. Phillips2 CK Consulting Associates, LLC, Saint Helena Island, SC; 2EMD Serono, Inc, Rockland, MA
1
Background: Administrative claims data provide information on outcomes in actual clinical care settings in a broader patient population. Objectives: To evaluate resource use associated with outpatient management of patients with multiple sclerosis (MS) newly initiating subcutaneous interferon beta-1a (scIFNβ1a) vs. oral disease-modifying drugs (DMDs; ie, teriflunomide, fingolimod, dimethyl fumarate) using real-world data. Methods: Patients from the IMS LifeLink PharMetrics Plus™ Database between 1/1/2012 and 6/30/2013 met the inclusion criteria: MS diagnosis (ICD-9CM: 340.xx); initiation of scIFNβ1a, teriflunomide, fingolimod, or dimethyl fumarate (1st claim = index date); continuous eligibility 12 months pre- and post-index; no DMD 12 months pre-index (treatmentnaïve); and age 18–63 years. Resource use associated with outpatient management was assessed 12 months following DMD initiation and included outpatient visits, neurologist visits, magnetic resonance imaging (MRI), liver function tests (LFTs), and complete blood counts (CBCs). Generalized linear models with gamma distribution and log link assessed resource use controlling for age, sex, region, and clinically meaningful disease severity measures (ie, 90-day pre-index indicators for relapse, neurologist visits, and MRI). Results: 1665 patients (686 scIFNβ1a, 118 teriflunomide, 455 fingolimod, and 406 dimethyl fumarate) met inclusion criteria (mean age = 44.4 years; 75.5% female). After adjustment for demographic and 90-day pre-index indicators, the estimated mean number of outpatient visits per patient was lowest for scIFNβ1a (18.2) vs. fingolimod (21.1; P = .002), dimethyl fumarate (21.5; P = .001), and teriflunomide (22.9; P = .003). On average, patients receiving scIFNβ1a had fewer MS-related outpatient visits (6.6) vs. dimethyl fumarate (8.7; P < .001), fewer neurologist visits (5.3) vs. fingolimod (6.2; P = .010), and fewer MRIs (0.54) vs. fingolimod (0.72; P = .018) and dimethyl fumarate (0.77; P = .007). The mean number of LFTs was lower for dimethyl fumarate (0.45) vs. scIFNβ1a (0.63; P = .037) and higher for teriflunomide (1.16; P = .010 vs. scIFNβ1a). The mean number of CBCs did not differ among DMDs. Conclusions: In this realworld population, after controlling for demographics and pre-index clinically meaningful indicators of disease severity, several resource use measures associated with outpatient management were lower in patients initiating scIFNβ1a compared with patients initiating oral DMDs. Supported by: EMD Serono, Inc, Rockland, MA (a business of Merck KGaA, Darmstadt, Germany), Pfizer Inc, New York, NY Disclosure: Chris M. Kozma: EMD Serono, Inc (grant/research support). Frederick Munschauer, Amy L. Phillips: EMD Serono, Inc (employee). Keywords: Disease-modifying treatments in MS (DX14) Cost of Patients with Multiple Sclerosis Newly Initiating Subcutaneous Interferon Beta-1a Versus Oral Disease-Modifying Drugs—A Real-World Assessment Chris M. Kozma,1 Frederick Munschauer,2 Amy L. Phillips2 CK Consulting Associates, LLC, Saint Helena Island, SC; 2EMD Serono, Inc, Rockland, MA
1
Background: Administrative claims datasets can provide information about the costs associated with medical treatments in real-world settings. This information may offer additional insights about the comparative impact and value of treatments, which may assist in optimizing patient care. Objectives: To utilize real-world data to evaluate costs among patients with multiple sclerosis (MS) initiating subcutaneous interferon beta-1a (scIFNβ1a) vs. oral disease-modifying drugs (DMDs; ie, teriflunomide, fingolimod, dimethyl fumarate). Meth-
ods: Patients with third-party payer coverage were identified from the IMS LifeLink PharMetrics Plus™ Database from 1/1/2012 to 6/30/2013. Inclusion criteria were: MS diagnosis (ICD-9-CM: 340. xx); initiation of scIFNβ1a, teriflunomide, fingolimod, or dimethyl fumarate (1st claim = index date); continuous eligibility 12 months pre- and post-index; no DMD 12 months pre-index (treatment-naïve); and age 18–63 years. Total (all-cause) and medical costs (excluding DMD costs) were assessed during the 12-month post-index period (reported in 2014 US dollars). Generalized linear models with gamma distribution and log link assessed cost controlling for demographics (ie, age, sex, and region) and clinically meaningful measures of disease severity (ie, 90-day pre-index indicators for relapse, neurologist visits, and MRI). Results: A total of 1665 patients (686 scIFNβ1a, 118 teriflunomide, 455 fingolimod, and 406 dimethyl fumarate) met inclusion criteria (mean age = 44.4 years; 75.5% female; 28.0% Northeast, 35.0% Midwest, 29.8% South, and 7.1% West). After adjustment for demographics and clinically meaningful disease severity indicators, the estimated least square mean 12-month total cost for scIFNβ1a was $57,558 compared with teriflunomide ($55,414; P = .4977), fingolimod ($69,478; P < .0001), and dimethyl fumarate ($69,798; P < .0001). The estimated least square mean 12-month medical cost for scIFNβ1a was $13,562 compared with fingolimod ($15,840; P = .0234), teriflunomide ($17,148; P = .0350), and dimethyl fumarate ($20,987; P < .0001). Conclusions: In this real-world MS patient population, after controlling for demographics and clinically meaningful measures of disease severity, 12-month total cost was significantly lower in patients initiating scIFNβ1a compared with those initiating fingolimod or dimethyl fumarate, and 12-month medical cost was significantly lower in patients initiating scIFNβ1a compared with patients initiating any oral DMD. Supported by: EMD Serono, Inc, Rockland, MA (a business of Merck KGaA, Darmstadt, Germany), Pfizer Inc, New York, NY Disclosure: Chris M. Kozma: EMD Serono, Inc (grant/research support). Frederick Munschauer, Amy L. Phillips: EMD Serono, Inc (employee). Keywords: Disease-modifying treatments in MS, Economic issues and MS (DX15) Comparison of Costs and Health Resource Utilization in Multiple Sclerosis Patients Treated with Disease-Modifying Therapies Jacqueline Nicholas,1 Aaron Boster,2 Wei-Shi Yeh,3 Robert Garland,3 Monica A. Fay,4 Ravi Iyer,3 Andrew Lee3 Health Economics & Outcomes Research, Novartis Pharmaceutical Corporation, East Hanover, NJ; 2OhioHealth Neurological Physicians, Columbus, OH; 3Global Health Economics and Outcomes Research, Biogen, Cambridge, MA; 4US Medical Affairs, Biogen, Weston, MA 1
Background: Disease-modifying therapies (DMTs) have dramatically changed the disease management of multiple sclerosis (MS). However, literature has limited information on the relative economic value of different DMTs in a real-world setting. Objectives: To compare the change in costs and health resource utilization of MS patients who initiated delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF), glatiramer acetate (GA), interferon (IFN), fingolimod (FTY), or teriflunomide (TER). Methods: A large administrative US-based claims database (MarketScan) was used. Adult MS patients (18–64 years) who initiated a DMT of interest in 2013 were included. Patients were not treated with DMT in the year prior to the date of DMT initiation (index date). Total health-care cost and nonprescription medical cost were compared for 1 year pre- and post-index date. Difference-in-differences estimate was used to assess the difference in cost between DMF and other DMTs over time while adjusting for demographics and Charlson Comorbidity Index (CCI). Results: Among the patients previously untreated with a DMT, a total of 1048 initiated DMF, 891 GA, 765 IFN, 207 FTY, and 170 TER. Baseline differences between these groups were seen in age (45.4, 43.2, 43.7, 44.4, and 48.6, respectively; P < .0001), CCI (0.65, 0.78, 0.73, 0.48, and 0.69, respectively; P = .02), and annual health-care cost before the index date ($21,905, $17,646, $16,823, $23,541, and $20,130, respectively; P < .01). Total annual health-care cost increased by $38,561, $45,559, $44,942,
International Journal of MS Care 35
Posters: Disease Modification $53,626, and $43,137 after the initiation of DMF, GA, IFN, FTY, and TER, respectively (P < .01). Among these groups, the reduction in annual nonprescription medical cost was $6,747 for DMF, $1,453 for GA, $2,746 for IFN, $4,246 for FTY, and $581 for TER (P < .01). The difference between DMF and other DMTs remains consistent after controlling for confounders. Conclusions: DMF had the lowest increase in total health-care cost and the highest reduction in nonprescription medical cost among the DMTs compared. Supported by: Biogen Disclosure: Jacqueline Nicholas: Biogen, Novartis, Genzyme, Teva, National Multiple Sclerosis Society, Multiple Sclerosis Association of America and Prime Med CME (consulting fees). Aaron Boster: Merck Serono, Biogen, Novartis, SunPharma, Roche, Genetech, National Multiple Sclerosis Society, NIH, Medtronic (consulting fees). Wei-Shi Yeh, Robert Garland, Monica A. Fay, Ravi Iyer, Andrew Lee: Biogen (employee, stockholder). Keywords: Disease-modifying treatments in MS, Economic issues and MS, Realworld evidence
Pharmaceuticals, Opexa Therapeutics, Novartis, Nuron, Roche (consulting fees); Genzyme, Hoffmann-LaRoche, Merck-Serono, Nuron, Perceptives, Sanofi-Aventis, Canadian Institute of Health Research, Multiple Sclerosis Society of Canada (grant/research support). Keywords: Clinical outcomes, Disease-modifying treatments in MS, Imaging and MS
(DX16) Four or More Active T2 Lesions at 6 Months Predicts Future Relapse/Disability in Patients with Relapsing Multiple Sclerosis on Placebo But Not Interferon Beta-1a Subcutaneously Three Times Weekly: Post Hoc PRISMS Analyses
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly reduced disease activity versus subcutaneous interferon beta-1a (SC IFNβ-1a) over 2 years in patients with highly active relapsing-remitting multiple sclerosis (RRMS) at baseline despite prior therapy. Improvements in clinical and magnetic resonance imaging (MRI) endpoints in this subgroup were durable over 4 years in an ongoing extension study (NCT00930553), despite most receiving no therapy since month 12. Objectives: To examine 5-year efficacy of alemtuzumab in the highly active subgroup, including those who received no additional treatment after the initial 2 alemtuzumab courses. Methods: Highly active disease was defined as ≥2 relapses in the year before randomization and ≥1 gadolinium-enhancing lesion at baseline. Patients randomized to alemtuzumab in the core study received 2 annual courses at months 0 and 12. In the extension, patients could receive alemtuzumab retreatment for relapse and/or MRI activity, or another disease-modifying therapy (DMT). No evidence of disease activity (NEDA) was defined as absence of clinical (relapse and 6-month confirmed disability progression) and MRI disease activity. Results: The extension enrolled 92/103 (89%) alemtuzumab patients with highly active disease at core study baseline. Over 5 years, 57 patients (62%) had no alemtuzumab retreatment or other DMT. In the extension (years 3–5), annualized relapse rate (ARR) was 0.18; 54% and 47% had no evidence of clinical and MRI disease activity, respectively. NEDA was observed in 54%, 52%, and 54% of patients in years 3, 4, and 5, and 26% had sustained NEDA over years 3–5. Six-month sustained reduction in disability (SRD) was achieved by 45% of patients over years 0–5. Among patients with no retreatment or other DMT since the initial 2 alemtuzumab courses, ARR in the extension (years 3–5) was 0.04, and 76% and 52% had no evidence of clinical and MRI disease activity, respectively. In this cohort, NEDA was observed in 71%, 63%, and 67% of patients in years 3, 4, and 5, respectively, and 41% had NEDA sustained over years 3–5. SRD was achieved by 53% over years 0–5. Conclusions: Efficacy of alemtuzumab in patients with highly active disease despite prior therapy was superior to that of SC IFNβ-1a in the core study and was durable in the extension through year 5 despite the majority not receiving treatment since month 12. These results suggest that alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continued treatment for highly active RRMS. Supported by: Genzyme, a Sanofi company; Bayer HealthCare Pharmaceuticals Disclosure: Barry A. Singer: Acorda, Bayer, Biogen, EMD Serono, Genzyme, Pfizer, Novartis, Teva (consulting fees); Acorda, Biogen, Genzyme, MedImmune, Novartis, Roche (grant/research support). Stephen Krieger: Acorda, Bayer, Biogen, Genentech, Genzyme, Novartis, Serono, Takeda, Teva (consulting fees); Biogen (fees for non-CME services from commercial interests or their agents). Regina Berkovich: Acorda, Avanir, Bayer, Biogen, Genentech, Genzyme, Novartis, Teva (consulting fees); Acorda, Avanir, Bayer, Biogen, Genzyme, Novartis, Teva (commercial speaker). Mark S. Freedman: Bayer HealthCare, Genzyme (grant/research support); Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation, EMD Canada (consulting fees). David H. Margolin, Karthinathan Thangavelu: Sanofi Genzyme (employee). Aaron Boster: Biogen, Novartis, Teva, Genzyme, Medtronic,
Anthony Traboulsee,1 Regina Berkovich,2 Hao Zhang,3 Fernando Dangond,4 David Li1 University of British Columbia, Vancouver, BC, Canada; 2University of Southern California, Los Angeles, CA; 3EMD Serono, Inc, Rockland, MA; 4EMD Serono, Inc, Billerica, MA 1
Background: In PRISMS-2, interferon beta-1a (IFNβ-1a) given subcutaneously (SC) three times weekly (tiw) reduced T2 lesions, relapses, and disability progression versus placebo in patients with relapsing multiple sclerosis (RMS). Objectives: To examine relationships between active T2 lesion numbers and subsequent clinical events in patients receiving IFNβ-1a SC tiw or placebo. Methods: Patients were randomized to IFNβ-1a 44 μg SC tiw, IFNβ-1a 22 µg SC tiw (not examined here), or placebo for 2 years, undergoing magnetic resonance imaging (MRI) scans biannually. In a 2-year extension, patients switched from placebo to IFNβ-1a SC or continued IFNβ-1a SC. Post hoc between-treatment comparisons of annualized relapse rate (ARR), according to the number of active T2 lesions on MRI scans at month 6 (0, ≥1, 0–1, ≥2, or ≥4 lesions), were performed using a negative binomial model; relapses (yes/no) and disability progression were compared using logistic regression. Results: Among placebo patients (n = 187), ARR over 2 years was higher for those with ≥4 versus 0–1 (rate ratio 1.54; P = .0013), ≥2 versus 0–1 (1.28; P = .0394), and ≥4 versus 0 (1.58; P = .0045) active T2 lesions at month 6; no significant effect was seen in IFNβ-1a 44 µg SC tiw patients (n = 184). Similar results were seen over 4 years: active T2 lesions (≥4 vs. 0–1, ≥2 vs. 0–1, ≥4 vs. 0) were associated with higher ARR in the placebo/delayed treatment group only. Placebo/delayed treatment patients were significantly more likely to have had a relapse by year (Y) 2 and Y4 with ≥2 versus 0–1, ≥1 versus 0, and ≥4 versus 0 active 6-month T2 lesions, and to have relapses at Y4 with ≥4 versus 0–1 active 6-month T2 lesions. For patients in the placebo/delayed treatment group, the presence of ≥2 versus 0–1 active 6-month T2 lesions predicted disability progression at Y2 and Y4, and the presence of ≥4 versus 0–1 active 6-month T2 lesions predicted progression at Y2. No comparisons predicted relapse or disability in IFNβ-1a 44 µg SC tiw patients at Y2 or Y4. Conclusions: Greater T2 lesion activity predicted worsened clinical results in patients with RMS receiving placebo/delayed treatment but not in those receiving IFNβ-1a 44 µg SC tiw. Patients with multiple T2 lesions after 6 months on treatment might be expected to be treatment nonresponders; however, this analysis suggests that the presence of multiple T2 lesions after 6 months does not predict poorer outcomes in patients treated with IFNβ-1a 44 µg SC tiw. Supported by: EMD Serono, Inc, Rockland, MA (a business of Merck KGaA, Darmstadt, Germany), Pfizer Inc, New York, NY Disclosure: Anthony Traboulsee: Genzyme, Roche, Chugai, Biogen (grant/ research support); Roche, Genzyme, Teva, Biogen (consulting fees). Regina Berkovich: Nothing to disclose. Hao Zhang: EMD Serono, Inc (employee, ownership interest). Fernando Dangond: EMD Serono, Inc (employee). David Li: Vertex
(DX17) Patients with Highly Active Relapsing-Remitting Multiple Sclerosis Despite Prior Therapy Show Durable Improvement with Alemtuzumab over 5 Years Barry A. Singer,1 Stephen Krieger,2 Regina Berkovich,3 Mark S. Freedman,4 David H. Margolin,5 Karthinathan Thangavelu,5 Aaron Boster,6 on behalf of the CARE-MS I and CARE-MS II Investigators The MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO; Icahn School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY; 3Keck School of Medicine, University of Southern California, Los Angeles, CA; 4 University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; 5 Genzyme, a Sanofi company, Cambridge, MA; 6OhioHealth Neurological Physicians, Columbus, OH 1 2
International Journal of MS Care 36
Posters: Disease Modification Mallinckrodt (consulting fees, fees for non-CME services from commercial interests or their agents). Keywords: Disease-modifying treatments in MS (DX18) Delayed-Release Dimethyl Fumarate Does Not Adversely Affect the Pharmacokinetics of a Commonly Used Oral Contraceptive: A Drug-Drug Interaction Study Bing Zhu,1 Karin Galil,1 Ivan Nestorov,1 Guolin Zhao,1 Venkata Meka,1 Jeanelle Kam,2 Sarah I. Sheikh1 Biogen, Cambridge, MA; 2Covance Clinical Research Unit, Dallas, TX
1
Background: As women of childbearing age make up a large proportion of the multiple sclerosis (MS) population, it is important to study the potential drug-drug interaction between the MS therapy delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) and oral contraceptives. Objectives: To evaluate the effect of DMF 240 mg twice daily (bid) on the pharmacokinetics of norgestimate/ethinyl estradiol once-daily (qd) in healthy women. Methods: Forty-six healthy volunteers were enrolled in this randomized, open-label, crossover, drug-drug interaction study. Of the 46 subjects enrolled, 32 completed the study. All subjects received norgestimate/ethinyl estradiol qd in the Lead-in Period; eligible subjects were then randomized 1:1 to one of two treatment sequences. In sequence 1, subjects received norgestimate/ethinyl estradiol qd and DMF 240 mg bid (norgestimate/ethinyl estradiol+DMF) in period 1, then norgestimate/ethinyl estradiol qd alone in period 2. In sequence 2, these regimens were reversed. Each period was 28 days in duration; DMF was administered only for the first 21 days when applicable. To evaluate the pharmacokinetic profiles of norgestimate (via its primary metabolite, norelgestromin) and ethinyl estradiol, blood samples were collected pre-dose and at multiple time points (up to 24 hours) post-first dose on day 21 of both treatment periods. Results: Mean plasma norelgestromin and ethinyl estradiol concentration profiles were superimposable following norgestimate/ ethinyl estradiol alone and norgestimate/ethinyl estradiol+DMF treatments. There was no statistically significant effect of DMF on the pharmacokinetic parameters of norelgestromin and ethinyl estradiol, with 90% confidence intervals of geometric mean ratios for AUC0-τ and Cmax contained within the 0.8 to 1.25 range. The median values of plasma progesterone, a pharmacodynamic endpoint, were also comparable for each treatment (norgestimate/ethinyl estradiol alone and norgestimate/ethinyl estradiol+DMF). In addition, the safety profile of concurrent use of norgestimate/ethinyl estradiol and DMF was consistent with that observed for DMF in previous studies. Conclusions: No impact of DMF on the pharmacokinetics or pharmacodynamics of norgestimate/ethinyl estradiol was observed. Supported by: Biogen Disclosure: Bing Zhu, Guolin Zhao, Sarah I. Sheikh: Biogen (employee, ownership interest). Karin Galil: Biogen (consulting fees). Ivan Nestorov, Venkata Meka: Biogen (employee, ownership interest). Jeanelle Kam: Covance (employee). Keywords: Dimethyl fumarate, Drug-drug interactions, Disease-modifying treatments in MS (DX19) Disease Activity Is Associated with Nonadherence in Dimethyl Fumarate Compared to Fingolimod in Clinical Practice Carrie M. Hersh,1 Samuel Cohn,2 Claire Hara-Cleaver,3 Robert Bermel,3 Robert J. Fox3, Jeffrey A. Cohen,3 Daniel Ontaneda3 Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas, NV; 2Cleveland Clinic, Cleveland, OH; 3The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH 1
Background: Dimethyl fumarate (DMF) and fingolimod (FTY) are frequently used oral disease-modifying therapies for relapsing multiple sclerosis (MS). Phase 3 trials established these agents as effective and generally well tolerated. Using propensity score (PS) analysis, our previous 12-month experience showed comparable efficacy and adherence, though DMF had greater radiographic disease activity and side effects early after treatment initiation. In our cohort, the direct relationship between nonadherence and disease activity on these two oral agents remained unclear. Objectives: To assess the effect of nonadherence on disease activity in DMF compared to FTY
in patients with MS in clinical practice. Methods: Patients followed in a large academic MS center who were prescribed DMF (n = 458) or FTY (n = 317) within 12 months of respective FDA approval and had 12-month follow-up data available were identified. We also identified a subgroup of DMF (n = 99) and FTY (n = 64) patients with disease activity, defined as clinical relapse and/or new radiographic disease activity (eg, new T2 and/or gadolinium-enhancing lesions). Effects of nonadherence in patients with disease activity were compared between treatment groups using PS analysis and an adjusted linear regression model. Degree of covariate balance was determined by comparing standardized differences before and after propensity adjustment. PS weighting showed favorable covariate balance between DMF and FTY groups. Reason for nonadherence, eg, intolerability, forgetfulness, and cost/insurance issues, was also collected. Results: In our subgroup population of patients with disease activity, 49 DMF and 24 FTY patients were nonadherent on respective therapies during the initial 12 months of treatment. PS weighting showed higher risk of nonadherence in DMF vs. FTY patients (difference estimate = 8.12, 95% CI = 2.88-13.37, P = .003). The most common reason for adherence issues in this cohort was forgetfulness (DMF n = 33/49; FTY n = 13/24). Nonadherence due to intolerability was unexpectedly low in the DMF group (n = 6/49). Conclusions: In our patient cohort, disease activity was associated with increased nonadherence in DMF patients compared to their FTY counterparts, the most common reason being forgetfulness. Counseling measures on importance of adequate adherence with a twicedaily medication should be stressed in clinical practice. Supported by: Biogen, National Multiple Sclerosis Society Sylvia Lawry Physician Clinical Fellowship Award FP 1788-A-1 Disclosure: Carrie M. Hersh: National Multiple Sclerosis Society (grant/research support). Samuel Cohn: Nothing to disclose. Claire Hara-Cleaver: Biogen Idec, Teva Neuroscience, EMD Serono, Acorda Pharmaceuticals, Novartis, Genzyme (consulting fees). Robert Bermel: Biogen Idec, Novartis, Teva, Genzyme, Questcor (consulting fees, grant/research support). Robert J. Fox: Biogen, Novartis (advisory board); Biogen, MedDay, Novartis, Questcor, Teva, Xenoport (consulting fees). Jeffrey A. Cohen: Biogen Idec, EMD Serono, Genzyme, Novartis, Receptos, Synthon, Teva, Vaccinex (consulting fees). Daniel Ontaneda: NIH (grant/research support). Keywords: Adherence, Disease-modifying treatments in MS (DX20) Evaluating Effect of Dimethyl Fumarate on Leukocytes Among Caucasian, African American, and Hispanic American Patients with Multiple Sclerosis Carrie L. Sammarco,1 Lana Zhovtis Ryerson,1 Ashley Akhter,2 Tamar Bacon,1 Lisa Laing,1 Ilya Kister1 MS Comprehensive Care Center, New York University Langone Medical Center, New York, NY; 2New York University School of Nursing, New York, NY 1
Background: Dimethyl fumarate (DMF) demonstrated significant efficacy in two randomized clinical trials for treatment of relapsingremitting multiple sclerosis (RRMS). However, trials included few patients of African American (AA) and Hispanic American (HA) backgrounds. Recent reports of progressive multifocal leukoencephalopathy (PML) in patients treated with DMF, possibly related to leukopenia developing after the start of the drug, is of concern. Identifying cohorts of patients at increased risk of leukopenia related to DMF is imperative to potentially reduce risk in clinical practice. Objectives: To evaluate DMF effect and differences on leukocytes in patients with MS in Caucasians, AAs, and HAs at the New York University MS Center, which serves an ethnically diverse patient population. Methods: Retrospective chart review was performed of all clinic patients who were started on DMF in the first year of drug availability. Race was derived from patient self-description. Relapses and new T2 and gadolinium-enhancing lesions were recorded 1 year prior to and while on DMF therapy. The entire cell-based counts (CBC) and differentials were captured and reviewed for patients on DMF therapy to evaluate leukocyte counts as well as other cell lines (neutrophils, platelets, hemoglobin, and mean corpuscular volume), which may point to bone marrow suppression. Furthermore, full medication lists were obtained for review to evaluate the role of other agents that may be contributing to leukopenia. Results of multivariate analyses
International Journal of MS Care 37
Posters: Disease Modification will be presented. Results: Initial analysis of data revealed the following: There were 256 MS patients who were started on DMF with available CBC. The average age was 45 years (range 21–79); 74% were women. Ethnicity was available for 85% of patients; 56% were Caucasian, 17% AA, and 12% Hispanic. Mean duration of MS symptoms was 6 years (range 1–55). The mean duration of treatment was 14 months. 10% of patients were drug naïve. The discontinuation rate was 20%, with 6% related to leukopenia (Caucasian 2%, AA 0%, Hispanic 2%). Grade 2 lymphopenia was seen in 15% of patients (n = 39); Grade 3 in 9% (n = 23); and Grade 4 in 2% (n = 4). Evaluation of statistical differences among the racial groups, other cell line involvement, and role of concomitant medications will be presented. Conclusions: DMF efficacy and tolerability appears to be similar among Caucasians, African Americans, and Hispanic Americans. Evaluation of DMF-related leukopenia among the three racial groups may help identify high-risk group or other contributing factors that may predispose patients to this complication. Supported by: None Disclosure: Carrie L. Sammarco: Biogen (consulting fees, grant/research support). Lana Zhovtis Ryerson: Biogen (grant/research support, consulting fees), Teva (consulting fees). Ashley Akhter, Tamar Bacon: Nothing to disclose. Lisa Laing: Biogen (grant/research support). Ilya Kister: Biogen (scientific advisory board), GuthyJackson Charitable Foundation, National Multiple Sclerosis Society, Biogen, Serono, Novartis (grant/research support). Keywords: Disease-modifying treatments in MS (DX21) Relapses in Multiple Sclerosis Patients Treated with Dimethyl Fumarate with No Variation in Lymphocyte Counts Cecilie Fjeldstad, Tania Reyna, Jennifer Smith, Tony Sharp, Gabriel Pardo MS Center of Excellence, Oklahoma Medical Research Foundation, Oklahoma City, OK
Background: Dimethyl fumarate (DMF, Tecfidera) has proven to be effective in relapsing multiple sclerosis (MS) by reducing clinical relapses and magnetic resonance imaging (MRI) activity. In the pivotal clinical trials the proportion of patients with a relapse was 29%. A drop of 30% in the mean lymphocyte counts (LC) was identified, with the majority remaining above the lower limit of normal (0.9 × 109/L). A drop in LC to
