Tofacitinib Monotherapy in Rheumatoid Arthritis: Clinical Trials and Real-World Data Contextualization of Patients, Efficacy, and Treatment Retention.

Abstract

Purpose: To evaluate the characteristics, efficacy, and retention of tofacitinib monotherapy in patients with rheumatoid arthritis using data from randomized controlled trials (RCTs) and real-world data (RWD).

Patients and methods: Three patient groups receiving tofacitinib 5 mg twice daily (BID) monotherapy were defined for post hoc RCT/long-term extension (LTE) analyses: (1) disease-modifying antirheumatic drug (DMARD)-inadequate responder patients from phase 3/3b/4 RCTs; (2) methotrexate-naïve patients from a phase 3 RCT; and (3) index study patients continuing in an LTE study. Outcomes included low disease activity (LDA)/remission rates defined by Clinical Disease Activity Index (CDAI); Disease Activity Score in 28 joints (DAS28-4), erythrocyte sedimentation rate; DAS28-4, C-reactive protein (DAS28-4[CRP]); and rates of/time to discontinuation due to lack of efficacy/adverse events. RWD were identified by non-systematic literature searches of PubMed, Embase, and American College of Rheumatology/European Alliance of Associations for Rheumatology congress abstracts (2012-2022).

Results: RCT/LTE analyses included 1000/498 patients receiving tofacitinib 5 mg BID monotherapy. Baseline disease activity was high; patients tended to receive concomitant glucocorticoids; most were biologic DMARD-naïve. CDAI LDA rates were 32.2-62.2% for Groups 1/2 (months 3-12) and 64.0-70.7% for Group 3 (months 12-72). In Groups 1, 2, and 3, 4.0%, 15.6%, and 27.7% of patients, respectively, discontinued tofacitinib monotherapy due to lack of efficacy/adverse events. From 11 RWD publications, 16.6-66.1% received tofacitinib monotherapy. Consistent with clinical data, tofacitinib monotherapy effectiveness (month 6 CDAI LDA, 30.2%; month 3 DAS28-4[CRP] remission, 53.4%) and persistence were observed in RWD, with retention comparable to tofacitinib combination therapy.

Conclusion: Tofacitinib monotherapy demonstrated clinically significant responses/persistence in RCT/LTE analyses, with effectiveness observed and persistence comparable to combination therapy in RWD.

Trial registration: NCT00814307, NCT02187055, NCT01039688, NCT00413699, NCT00661661 (ClinicalTrials.gov).