Background/Purpose: Tumor necrosis factor inhibitors (TNFi) therapies were one of the major advances in the treatment of Ankylosing Spondylitis (AS) patients. For infliximab, anti-drug antibodies (ADA) seem to contribute to drug failure but it is not known its long term influence on tapering, drug survival and switching. We aim to evaluate the frequency and long-term kinetics of anti-infliximab antibodies (anti-IFX) and its influence on drug survival, treatment failure, infusion reaction, tapering strategy and in subsequent treatment with a second TNFi.

Methods: A prospective cohort of 60 AS patients under infliximab (IFX) as their first biological therapy were evaluated retrospectively regarding clinical and laboratorial data, IFX levels and anti-IFX, both by ELISA, at baseline and after 6, 12-14, 22-24, 48-54, 96-102 weeks and immediately before the switching, treatment withdrawal or the end of the study. The switching group (to another TNFi), were further evaluated after 3 and 6 months. For the tapering group, additional clinical and laboratory data were assessed before tapering strategy and at tapering failure or withdrawal of the drug. Biological agent and anti-IFX antibodies quantification was performed according to the manufacturer’s protocol of the kits (Promonitor® IFX and Promonitor ®anti-IFX).

Results: Anti-IFX were detected in 27 (45%) patients during follow-up and 85.1% in the first year. The concomitant use of methotrexate was negatively associated with anti-IFX (5.0 [18.5%] vs. 14.0 [42.4%]; p=0.048). Infusion reactions were more often observed in positive anti-IFX patients at 22-24 weeks (3.0 [21.4%] vs. 1.0 [2.2%]; p=0.020) and at 48-54 weeks (3 [20.0%] vs. 0 [0.0%]; p=0.034). Anti-IFX at 48-54 weeks was associated with treatment failure (7.0 [46.7%] vs. 4.0 [13.8%]; p=0.028) and lower overall IFX survival (54.9 months [CI 95% 26.3-83.4] vs. 148.9 months [CI 95% 123.5-174.4]; p< 0.001). Of note, for the tapering group (n=24) anti-IFX was associated with shorter survival of this strategy (9.9 months [IC 95% 4.0-15.8] vs 63.4 months [IC 95% 27.9-98.8]; p=0.004). In contrast, for patients who failed to IFX (n=29), anti-IFX positivity at the switching was related to a better clinical response to the second TNFi at 3 months (15.0 [83.3%] vs. 3.0 [27.3%]; p=0.005) and at 6 months (15 [83.3%] vs. 4 [36.4%]; p=0.017).

Conclusion: This study demonstrates that in spite of anti-IFX association with worse IFX performance, this marker was a predictor of 2nd TNFi good clinical response. We also provided novel data that anti-IFX is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision in these two treatment strategies. Additionally, concomitant use of methotrexate (MTX) may be recommended to reduce anti-IFX formation in AS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-infliximab-antibodies-as-a-marker-of-drug-survival-and-tapering-in-ankylosing-spondylitis-patients-12-years-follow-up/