Background/Purpose: Anti-TNF agents are efficacious in the treatment of ankylosing spondylitis (AS). The switch to another TNF blockage can be an alternative in cases of lack or loss of efficacy and side effects. There are, however, no clear evidence for a beneficial effect of co-therapy with conventional synthetic DMARDs in AS. The aim of this study was to determine the efficacy and predictors of anti-TNF switch in the long-term follow-up of AS patients, in a routine clinical care center.

Methods: Data from an ongoing longitudinal electronic database of AS patients under anti-TNF therapy between June 2004 and August 2013 were assessed. Demographic and clinical parameters, concomitant therapy and treatment responses by ASDAS were recorded. ASDAS remission(<1.3) and ASDAS inactive/moderate(<2.1) were analyzed to characterize the switch of TNF blockage. Final assessment of switch response excluded patients who underwent anti-TNF therapy less than 24 weeks and patients that stopped a given anti-TNF treatment course due to non-adherence, adverse events or infection (without further drug introduction).

Results: Of 117 AS patients treated with anti-TNF (mean treatment duration: 39.4 ± 30.1 months) 69(59%) received solely the first anti-TNF, 48(41%) switched to a second anti-TNF (58% failure and 42% side effects) and 13(11%) to a third anti-TNF (62% failure and 38% side effects).The choice of the second anti-TNF did not influence the maintenance of the therapy; it was comparable among patients who started and switched to monoclonal antibody (infliximab or adalimumab) and those who started with monoclonal antibody and switched to etanercept (66% vs. 77%, p=0.72). At the final assessment, 42 patients still under the first anti-TNF (non-switcher group) achieved more frequently ASDAS remission-ESR (62% vs. 36%, p=0.04) and ASDAS inactive/moderate-ESR (88% vs. 58%, p=0.03) than patients treated with more than one anti-TNF. The switch to a third anti-TNF resulted in a lower response rate with 25% reaching inactive/moderate disease activity (p<0.001) and 12.5% achieving ASDAS remission (p=0.03). Duration of the last anti-TNF treatment was comparable in all groups (p=0.24). Non-switchers achieved lower BASDAI (p=0.04) and BASFI (p=0.03) than switcher groups. Switchers due to failure or adverse effects were comparable regarding demographic and clinical parameters at baseline and at final assessment. The analysis of predictors at baseline revealed that non-switchers were more often treated with sulfasalazine (SSZ) (63.8% vs. 41.7%, p=0.02) than switcher patients. Further evaluation of the use of this drug revealed that non-switchers with pure axial involvement also used more frequently SSZ than switchers (70.8% vs.15% vs. p=0.03). In contrast, the frequency of SSZ use was comparable in non-switchers and switchers AS patients with peripheral involvement (58.1% vs. 48.7%, p=0.51).

Conclusion: This study provides novel evidence that SSZ comedication reduces anti-TNF switch in AS patients, particularly in those with pure axial disease.  The underlying mechanism remains unknown and may involve the prevention of anti-drug antibodies formation and/or an additional anti-inflammatory effect.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sulfasalazine-comedication-a-predictor-of-reduced-long-term-anti-tnf-switch-in-ankylosing-spondylitis/