Background/Purpose: In patients with rheumatoid arthritis (RA) who do not respond or lose response to a tumor necrosis factor inhibitor (TNFi), opinions are divided on whether it is better to try an alternative TNFi (cycling) or switch to a therapy with a different mode of action (swapping).The purpose of the review was to compare the effectiveness and safety of the cycling versus the swapping strategies as reported in observational studies.

Methods: We searched 4 electronic databases, sources of gray literature, and bibliographic references of relevant articles for observational studies evaluating the efficacy and safety of targeted therapies in adult RA patients who failed to respond to at least one TNFi. Studies were excluded if they were single-arm or had insufficient data to evaluate the outcomes of interest. Two independent reviewers selected studies, extracted data and evaluated study quality using the Newcastle-Ottawa Scale (NOS). Our primary outcome measure was change in Disease Activity Score of 28 joints (DAS28). We also evaluated the modified American College of Rheumatology 20%, 50% and 70% response criteria (mACR which excludes acute phase reactants) and total serious adverse events. All analyses were based on the random-effects model.

Results: Of 33,716 citations, 24 observational studies (n=10,074 patients) representing 14 countries, met the inclusion criteria. Eight were conference abstracts. Most publications (13 of 24) were based on registries. Most studies had a NOS score equal to or greater than 7 (out of 9) with comparability being the weakest domain. The mean age of patients was 48.7-62.8 years, the majority were females (78%) with a disease duration of 6-17.3 years and a baseline disability score 0.6-2.0. Sixteen studies evaluated cycling versus swapping directly of which 13 were suitable for analysis. Most compared TNFi to rituximab (10 of 13) with two studies investigating tocilizumab or abatacept and one comparing non-TNFi as a group. Other comparisons reported were: (i) cycling vs. another cycling alternative, (ii) swapping vs. another swapping alternative, and (iii) swapping monotherapy vs. swapping combined with cDMARDs. At 12 and 24 weeks, DAS28 score improved significantly in those swapping compared to those cycling (mean difference (MD) 0.89, 95% confidence interval (CI) 0.05 to 1.74 and MD 0.34 95% CI: 0.2, 0.48; respectively). Similar results were observed for the mACR50 favoring the swapping strategy at 24 weeks (OR = 1.45 95%CI: 1.06, 1.98). However, at 52 weeks no difference was observed. No statistically significant differences were observed between groups in the odds of achieving DAS28 remission, mACR20 or mACR70, or experiencing a serious adverse event.

Conclusion: Current evidence from observational studies shows greater improvements with the swapping strategy compared with the cycling strategy in terms of efficacy for RA patients failing their first TNFi. No differences were observed regarding safety. Data were not available for anakinra, certolizumab pegol, golimumab, or tofacitinib.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cycling-versus-swapping-in-patients-with-rheumatoid-arthritis-with-an-inadequate-response-to-at-least-one-tumor-necrosis-factor-alpha-inhibitor-a-systematic-review-and-meta-analysis-of-observational/