Study data published in Arthritis & Rheumatology support 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.
The safety and tolerability of tofacitinib were consistent with existing data. Safety events were similar in type and frequency for both tofacitinib doses, and the rates of discontinuation for any reason were similar across the 4 study cohorts. The most frequent reported adverse events were pneumonia (2.2%) for the tofacitinib 5 mg group and herpes zoster and urinary tract infection (1.3% for both) for the tofacitinib 10 mg group. A total of 11 deaths were recorded during the study, among which 6 were considered to be related or possibly related to study drug administration.
These data support the efficacy of tofacitinib 5 mg and 10 mg twice daily for the treatment of RA in conjunction with methotrexate. The safety profile of the drug was also consistent with existing data from prior randomized controlled trial on tofacitinib.
van der Heijde D, Strand V, Tanaka Y, et al. Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: clinical efficacy, radiographic and safety outcomes from the 24-month phase 3 ORAL scan study [published online January 22, 2019]. Arthritis Rheumatol. doi:10.1002/art.40803