Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia

Abstract

ImportanceThere is a need for observational studies to supplement evidence from clinical trials, and the target trial emulation (TTE) framework can help avoid biases that can be introduced when treatments are compared crudely using observational data by applying design principles for randomized clinical trials. Adalimumab (ADA) and tofacitinib (TOF) were shown to be equivalent in patients with rheumatoid arthritis (RA) in a randomized clinical trial, but to our knowledge, these drugs have not been compared head-to-head using routinely collected clinical data and the TTE framework.ObjectiveTo emulate a randomized clinical trial comparing ADA vs TOF in patients with RA who were new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD).Design, Setting, and ParticipantsThis comparative effectiveness study emulating a randomized clinical trial of ADA vs TOF included Australian adults aged 18 years or older with RA in the Optimising Patient Outcomes in Australian Rheumatology (OPAL) data set. Patients were included if they initiated ADA or TOF between October 1, 2015, and April 1, 2021; were new b/tsDMARD users; and had at least 1 component of the disease activity score in 28 joints using C-reactive protein (DAS28-CRP) recorded at baseline or during follow-up.InterventionTreatment with either ADA (40 mg every 14 days) or TOF (10 mg daily).Main Outcomes and MeasuresThe main outcome was the estimated average treatment effect, defined as the difference in mean DAS28-CRP among patients receiving TOF compared with those receiving ADA at 3 and 9 months after initiating treatment. Missing DAS28-CRP data were multiply imputed. Stable balancing weights were used to account for nonrandomized treatment assignment.ResultsA total of 842 patients were identified, including 569 treated with ADA (387 [68.0%] female; median age, 56 years [IQR, 47-66 years]) and 273 treated with TOF (201 [73.6%] female; median age, 59 years [IQR, 51-68 years]). After applying stable balancing weights, mean DAS28-CRP in the ADA group was 5.3 (95% CI, 5.2-5.4) at baseline, 2.6 (95% CI, 2.5-2.7) at 3 months, and 2.3 (95% CI, 2.2-2.4) at 9 months; in the TOF group, it was 5.3 (95% CI, 5.2-5.4) at baseline, 2.4 (95% CI, 2.2-2.5) at 3 months, and 2.3 (95% CI, 2.1-2.4) at 9 months. The estimated average treatment effect was −0.2 (95% CI, −0.4 to −0.03; P = .02) at 3 months and −0.03 (95% CI, −0.2 to 0.1; P = .60) at 9 months.Conclusions and RelevanceIn this study, there was a modest but statistically significant reduction in DAS28-CRP at 3 months for patients receiving TOF compared with those receiving ADA and no difference between treatment groups at 9 months. Three months of treatment with either drug led to clinically relevant average reductions in mean DAS28-CRP, consistent with remission.

Risk of dyslipidemia and major adverse cardiac events with tofacitinib versus adalimumab in rheumatoid arthritis: a real-world cohort study from 7580 patients

“…In contrast, adalimumab is an injectable tumor necrosis factor-alpha (TNF-α) inhibitor monoclonal antibody biologic that directly targets inflammatory cells and cytokines (Zullow et al, 2014;Panaccione et al, 2021;Huang et al, 2022;Zouboulis et al, 2023). Both drugs are widely used either alone or in combination strategies to manage RA symptoms and slow disease progression, often in side-by-side comparative studies (Zhang et al, 2014;Fleischmann et al, 2017;Deakin et al, 2023).…”

Chimeric antigen receptors: “CARs” in the fast lane for rheumatology

“…Although these therapies have resulted in major advances for the treatment of SLE there remains a need for therapies with capacity to induce reliable, long-lived drug-free remission. Combination therapies among approved agents are likely to be tested soon, yet our experience from other diseases suggests that this approach may be difficult to pursue due to lack of support by sponsors [19,20].…”