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.

OBJECTIVE:

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The Phase 3, 24-month, placebo-controlled trial, ORAL Scan (NCT00847613), evaluated tofacitinib efficacy, including structural progression, and safety in patients with active RA and methotrexate inadequate response (MTX-IR). 12-month data were reported previously; Month 24 data from the completed study are reported here.

METHODS:

Patients were randomized 4:4:1:1 to tofacitinib 5 or 10 mg twice daily (BID), or placebo→tofacitinib 5 or 10 mg BID, with stable, background MTX. Patients receiving placebo advanced to tofacitinib at Month 3 (non-responders) or Month 6 (remaining patients). Clinical efficacy, structural progression, and treatment-emergent adverse events were evaluated. Analyses were performed on the full analysis set with observed or non-responder imputation with no advancement penalty for clinical efficacy and imputation by linear extrapolation for structural progression.

RESULTS:

Overall, 797 patients were treated; 539 (67.6%) completed 24 months' treatment. ACR20/50/70 responses, proportions of patients achieving DAS28-4(ESR)-defined remission or low disease activity, Clinical Disease Activity Index, Simplified Disease Activity Index and Boolean remission, and Health Assessment Questionnaire Disability Index were maintained through Months 12-24 and were similar between tofacitinib doses. Limited structural damage was observed at Months 12 and 24. Safety events were similar in type and frequency for both tofacitinib doses, and were consistent with those previously reported.

CONCLUSION:

In patients with RA receiving tofacitinib 5 or 10 mg BID plus MTX, clinical and radiographic treatment effects were sustained through Months 12-24. The safety profile was consistent with other tofacitinib studies. This article is protected by copyright. All rights reserved.