Session Information
Date: Monday, November 9, 2015
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Classic DMARDs are not
routinely prescribed for axial spondyloarthritis (SpA). Recent studies have
found that concomitant therapy with methotrexate (MTX) reduced immunogenicity
of TNF inhibitors (TNFi). However the effect of sulfasalazine (SSZ) on the
development of anti-drug antibodies (ADA) has not been properly studied. We
investigated the effect of MTX or SSZ on ADA development in a cohort of SpA
patients treated with Infliximab (Ifx) or Adalimumab (Ada).
Methods: SpA patients were enrolled from two prospective
observational cohorts, Spain (n=122) and The Netherlands (n=85). Out of 208 SpA
patients treated with Ifx or Ada we included 152 patients; 41(26.9%) with Ifx
and 111(73%) with Ada, who had drug and ADA levels measured during the first
year of TNFi therapy. Concomitant DMARD use was assessed at baseline.
Disease activity was measured at baseline, 6 months
and 1 year by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
Low disease activity (LDA) was defined as BASDAI<4 with normal CRP and
clinical improvement as ΔBASDAI>2. Serum drug levels were measured by
ELISA and ADA levels were measured by ELISA(Spain) and ABT(The Netherlands) and
samples were collected just before drug administration.
We performed the last observation carried forward
analysis to include patients who dropped-out before one year.
Results: The demographic and clinical characteristics
of the 152 SpA patients are shown in table1. ADA were detected in 26(17%) SpA
patients: 5(19%) treated with Ifx and 21(81%) with Ada. Only 3 patients with ADA were treated with DMARS concomitantly, specifically with SSZ.
The majority of ADA appeared at 6 months: 17 (65%)
patients and 9 (35%) developed ADA at 1 year. SpA patients treated with TNFi in
monotherapy developed more frequently ADA than patients treated concomitantly
with DMARDs: 23(26%) vs 3(4.7%), p=0.004. Patients treated with TNFi in
combination with MTX or SSZ developed ADA less frequently than patients treated
in monotherapy: 23(26%) vs 0(0%), p=0.02; 23(26%) vs 3(8%), p=0.03,
respectively). However we did not find significant differences in ADA development when we compared SpA patients treated with MTX vs SSZ: 0(0%) vs 3(8%),
p=0.54, respectively.
Most patients with ADA did not reach LDA during the first
year of treatment: 9(38%) ADA positive patients vs 70(62%) ADA negative
patients, p=0.04. ΔBASDAI was higher in ADA negative patients (Mdn, IQR): 2.2,
0.9-4 in ADA negative patients vs 1.1, 0.5-2.8 in ADA positive patients, p=0.03
Conclusion: In our cohorts of SpA patients treated
with Ifx or Ada the concomitant use of DMARDs (MTX or SSZ) is associated with
a lower development of ADA, which suggests a protective role of DMARDs to
prevent immunogenicity and, hence, to prevent a secondary failure of the
biological treatment.
Table 1: Clinical and demographic
characteristics of patients grouped by presence of anti-drug antibodies (ADA).
|
Characteristics |
ADA-(n=126) |
ADA+ (n=26) |
p value |
|
Men, n (%) |
75 (60%) |
9 (35%) |
ns |
|
Age(years), mean (SD) |
46.3±12.7 |
45.8±12.3 |
ns |
|
HLA B27 positive, n (%) |
91 (73%) |
18 (75%) |
ns |
|
Disease duration (years), mean (SD) |
10.7±9 |
11±10 |
ns |
|
Biological treatment duration (years) |
5.2±2.2 |
6±3 |
ns |
|
Baseline BASDAI, mean (SD) |
6.0±1.9 |
5.8±1.7 |
ns |
|
Baseline ESR, mean (SD) |
21.2±19 |
23.3±19.2 |
ns |
|
Baseline CRP, mean (SD) |
10.9±13.7 |
9.6±12 |
ns |
|
Extraaxial manifestation ( IBD,Psoriasis,Uveitis,Peripheral artritis) |
60 (48%) |
13 (50%) |
ns |
|
Concomitant treatment, n (%) |
|
|
|
|
Methotrexate (MTX) |
15 (12%) |
0 (0%) |
0.004 |
|
Sulfasalazine (SZS) |
33 (26%) |
3 (12%) |
|
|
MTX + SZS |
13 (10%) |
0 (0%) |
|
|
TNF inhibitors monotherapy |
65 (52%) |
23 (88%) |
SD: standard deviation
ns: no significant; unpaired t test
To cite this abstract in AMA style:
Martínez A, Plasencia-Rodriguez C, Pascual-Salcedo D, Kneepkens EL, Wolbink G, Villalba A, Jurado T, Peiteado D, Nuño L, Jochems A, Balsa A. The Effect of Sulfasalazine and Methotrexate on the Immunogenicity of Infliximab and Adalimumab in Patients with Spondyloarthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-effect-of-sulfasalazine-and-methotrexate-on-the-immunogenicity-of-infliximab-and-adalimumab-in-patients-with-spondyloarthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-sulfasalazine-and-methotrexate-on-the-immunogenicity-of-infliximab-and-adalimumab-in-patients-with-spondyloarthritis/