Clinical and radiographic treatment effects were sustained through 24 months in patients with RA receiving tofacitinib.
Study data published in Arthritis & Rheumatologysupport the efficacy and safety of tofacitinib with methotrexate through 24 months of treatment in patients with rheumatoid arthritis (RA).
Investigators conducted a phase 3, double-blind, 24-month randomized controlled trial with adult patients with RA and inadequate response to methotrexate. Patients were randomly assigned to receive one of the following: 5 mg tofacitinib twice daily; 10 mg tofacitinib twice daily; placebo advanced to tofacitinib 5 mg twice daily; or placebo advanced to tofacitinib 10 mg twice daily. Prior to study drug initiation, all patients had been receiving methotrexate continuously for ≥4 months and a stable dose for ≥6 weeks. Patients remained on a stable dose of methotrexate (≤25 mg weekly) through the present study. In the placebo treatment sequences, nonresponders — or those who achieved <20% improvement in swollen and tender joint counts — were advanced to tofacitinib at 3 months. The remaining patients receiving placebo were advanced at 6 months.
The following clinical efficacy parameters were evaluated: 20%, 50%, and 70% improvements in American College of Rheumatology criteria (ACR 20/50/70 response); mean change from baseline in the 28-joint Disease Activity Score based on erythrocyte sedimentation rate (DAS28-4[ESR]); remission, defined by DAS28-4(ESR) <2.6, clinical disease activity index ≤2.8, simplified disease activity index ≤3.3, and Boolean remission criteria; and low disease activity, defined by DAS28-4 (ESR) ≤3.2, clinical disease activity index ≤10, or simplified disease activity index ≤11. Mean changes from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) were also captured from baseline to 3 and 12 months. Structural progression was also assessed using mean changes from baseline in van der Heijde modified Total Sharp Score (mTSS). Treatment-emergent adverse events were reported according to treatment phase.
Of 797 patients initially selected for inclusion, 539 (67.6%) completed 24 months of treatment. Patients had similar demographic and baseline characteristics across the 4 treatment conditions. ACR20/50/70 responses, proportions of patients achieving remission or low disease activity, and improvements from baseline in DAS28-4(ESR) were maintained from 12 to 24 months. Specifically, 41% and 49% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, achieved low disease activity at 24 months. Further, low disease activity was achieved by 23% and 30%, respectively, of these same treatment groups. Between 12 and 24 months, ≥90% of patients showed no progression in structural damage (mTSS ≤0.5), with minimal changes from baseline for mTSS and erosion scores. The improvements in the HAQ-DI from baseline to 12 months were maintained through 24 months for both tofacitinib 5 mg and 10 mg.