DOI: 10.1111/apt.14541
LETTERS TO THE EDITORS
Letter: the addition of an immunosuppressant in patients with unsatisfactory response to vedolizumab 25.2 10.6 weeks of
EDITORS,
after a mean period of
We read with interest the article by Strik and colleagues1 showing
monotherapy (Table 1). All had multiple previous failures to
that the addition of an immunosuppressant to infliximab or adali-
immunomodulators and/or biologics. Patients were divided into 2
mumab in patients with inflammatory bowel disease (IBD) resulted in
groups. Group A included 9 patients with an incomplete control of
increased serum drug concentrations and regained clinical response.
intestinal symptoms despite the shortening of the administration
The efficacy of this strategy among patients on anti-TNFa
intervals of vedolizumab to every 4 weeks. After a mean follow-up
monotherapy was also clearly reported by other studies.2-4 Con-
of 20.4 3.7 weeks, 2 patients were in steroid-free remission, and
versely, very few data on the addition of an immunomodulator in
2 patients had a clinical response. The median time of achievement
case of unsatisfactory response to vedolizumab monotherapy have
of clinical response or steroid-free remission was 8 weeks (range:
been reported to date.
4-12 weeks). Group B included 4 patients with no or mild intestinal
From July 2016 to September 2017, all consecutive patients
vedolizumab
symptoms who added methotrexate due to the persistence of
treated with vedolizumab who added an immunomodulator due to
severe
an incomplete control of intestinal symptoms or to the persistence
21.5 11.5 weeks, 2 patients had a response on articular manifes-
articular
manifestations.
After
a
mean
follow-up
of
of severe articular manifestations were entered into a prospectively
tations. No adverse events were reported.
maintained database. During the study period, 146 patients with IBD
We have clearly distinguished 2 different clinical settings in
were treated with vedolizumab. Among them, 13 (10 with Crohn’s
which the addition of an immunomodulator to vedolizumab might be
disease and 3 with ulcerative colitis) added an immunomodulator
considered. First, some patients may experience a clinical benefit on
T A B L E 1 Overview of patients who added an immunosuppressant to vedolizumab following an incomplete control of intestinal symptoms (Group A, 9 patients) or due to the persistence of severe articular manifestations (Group B, 4 patients) Disease activity at
Time
Disease
Disease duration (y)
Disease location
Disease behaviour
Previous resections (no.)
VDZ + IM initiation (HBI/Mayo partial score)
A1 - M, 51
UC
17
E2
—
—
6 (Mayo)
Yes (2)
A2 - M, 27
CD
7
L3
B2
Yes (1)
8 (HBI)
Yes (2)
A3 - F, 52
CD
18
L3
pB1
Yes (2)
10 (HBI)
A4 - M, 51
CD
19
L3
B2
Yes (5)
A5 - M, 39
CD
19
L2
B1
A6 - M, 60
CD
22
L4
A7 - F, 44
UC
5
A8 - F, 25
CD
A9 - F, 28
Group/ Patient number Gender, Age
Previous anti-TNFa therapy (no. of lines)
between start of VDZ and addition of IM (wk)
IM (dosage)
Length of follow-up (wk)
Steroid-free remission
Clinical response
Articular response
28
MMF (1500 mg/day)
24
Yes
—
—
32
MMF (1500 mg/day)
20
No
Yes
—
Yes (2)
18
MTX (15 mg/weekly)
16
No
No
—
7 (HBI)
No
22
AZA (2 mg/Kg/day)
24
No
No
—
No
11 (HBI)
Yes (1)
18
AZA (2 mg/Kg/day)
24
No
Yes
—
B2
Yes (2)
5 (HBI)
Yes (2)
10
6-MP (1.5 mg/Kg/day)
16
Yes
—
—
E3
—
—
5 (Mayo)
Yes (2)
40
MMF (1500 mg/day)
24
No
No
—
9
L3
pB3
Yes (1)
8 (HBI)
Yes (2)
48
MMF (1500 mg/day)
16
No
No
—
CD
9
L2
B1
Yes (1)
12 (HBI)
Yes (2)
28
AZA (2 mg/Kg/day)
20
No
No
—
B10 - F, 57
CD
25
L3
B2
No
6 (HBI)
Yes (2)
14
MTX (25 mg/weekly)
16
—
—
No
B11 - M, 33
CD
8
L1
B2
Yes (1)
3 (HBI)
Yes (2)
18
MTX (15 mg/weekly)
38
—
—
Yes
B12 - F, 72
CD
2
L1
B1
No
7 (HBI)
Yes (1)
22
MTX (15 mg/weekly)
12
—
—
No
B13 - F, 61
UC
4
E3
—
—
1 (Mayo)
Yes (2)
30
MTX (15 mg/weekly)
20
—
—
Yes
MP, mercaptopurine; AZA, azathioprine; CD, Crohn’s disease; HBI, Harvey-Bradshaw Index; IM, immunosuppressant; MMF, mycophenolate mofetil; MTX, methotrexate; UC, ulcerative colitis; VDZ, vedolizumab. AP&T correspondence columns are restricted to letters discussing papers that have been published in the journal. A letter must have a maximum of 500 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http:// mc.manuscriptcentral.com/apt. 1040
|
© 2018 John Wiley & Sons Ltd
wileyonlinelibrary.com/journal/apt
Aliment Pharmacol Ther. 2018;47:1040–1048.
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LETTERS TO THE EDITORS
intestinal symptoms following treatment with vedolizumab, but se-
1041
LINKED CONTENT
vere articular manifestations may persist. In these cases, the use of an immunomodulator—particularly methotrexate—is only intended
This article is linked to Strik et al and Strik and D’Haens papers. To
to obtain a control of articular symptoms. Second, the addition of an
view these articles visit https://doi.org/10.1111/apt.13994 and
immunomodulator to vedolizumab monotherapy can improve clinical
https://doi.org/10.1111/apt.14570.
benefit when vedolizumab monotherapy did not obtain complete F. S. Macaluso
control of intestinal symptoms. In this line, a recent study by Alle-
R. Orlando
gretti et al5 showed that the addition of an immunomodulator to
S. Renna
vedolizumab was an independent predictor of clinical response or
C. Sapienza
remission at week 54 among patients with Crohn’s disease, while a
M. Ventimiglia
6
recent case series comprising 4 patients showed that the addition of methotrexate to vedolizumab did not obtain a clinical response
G. Rizzuto
and did not improve the pharmacokinetic profile of the drug. Conse-
M. Cottone
quently, we believe that our promising—but preliminary—results
A. Orlando
may be secondary to the addition of the therapeutic effect of the
IBD Unit, ‘‘Villa Sofia-Cervello’’ Hospital, Palermo, Italy
immunomodulator to that of vedolizumab, rather than to a pharma-
Email:
[email protected]
cokinetic benefit similar to that observed with anti-TNF combination therapies.7
REFERENCES
ACKNOWLEDGEMENTS Declaration of personal interests: Fabio Salvatore Macaluso: Lecture grant from MSD to Takeda Pharmaceuticals. Sara Renna: served as an advisory board member for AbbVie and MSD; received lecture grants from AbbVie, MSD, Takeda Pharmaceuticals, Zambon. Mario Cottone: received financial support for the organisation of a secondlevel Master degree in inflammatory bowel disease from AbbVie, MSD, Takeda Pharmaceuticals and Sofar. Ambrogio Orlando: served as an advisory board member for AbbVie, MSD, Takeda Pharmaceutical; received lecture grants from AbbVie, MSD, Takeda Pharmaceuticals, Sofar, Chiesi. Other authors: no conflicts of interest.
FUNDING INFORMATION None.
ORCID F. S. Macaluso S. Renna
http://orcid.org/0000-0001-5128-3846
http://orcid.org/0000-0001-8270-2978
1. Strik AS, van den Brink GR, Ponsioen C, et al. Suppression of antidrug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2017;45:1128-1134. 2. Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulatory to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11:444-447. 3. Macaluso FS, Sapienza C, Ventimiglia M, et al. The addition of an immunosuppressant after loss of response to anti-TNFa monotherapy in inflammatory bowel disease: a two-year study. Inflamm Bowel Dis. 2017; in press. 4. Orlando A, Renna S, Rizzuto G, et al. Selective use of combination therapy in patients with infliximab-resistant inflammatory bowel disease: data from a tertiary referral center. Clin Gastroenterol Hepatol. 2016;14:914. 5. Allegretti JR, Barnes EL, Stevens B, et al. Predictors of clinical response and remission at 1 year among a multicenter cohort of patients with inflammatory bowel disease treated with vedolizumab. Dig Dis Sci. 2017;62:1590-1596. 6. Gouynou C, Peyrin-Biroulet L. Letter: addition of methotrexate neither restores clinical response nor improves the pharmacokinetic profile of vedolizumab-treated patients. Aliment Pharmacol Ther. 2017;46:1019-1020. 7. Macaluso FS, Cottone M, Orlando A. The selective use of combination therapy in patients with inflammatory bowel disease resistant to antiTNF: to whom, how and how long? J Crohns Colitis. 2016;10:1451.
DOI: 10.1111/apt.14570
Letter: the addition of an immunosuppressant in patients with unsatisfactory response to vedolizumab—Authors’ reply EDITORS,
effect of adding an immunomodulator to vedolizumab monother-
We thank Macaluso and colleagues for their interest in our
apy in a small group of IBD patients (n = 13). Unfortunately,
paper.1,2 In their letter the authors describe the beneficial
only clinical response and steroid-free remission rates were © 2018 John Wiley & Sons Ltd
