Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for RA. The efficacy and safety of tofacitinib were evaluated in patients (pts) with active RA in Phase 3 trials. Primary efficacy analyses have previously been described.^1,2 Here we show patient-reported outcomes (PROs) from two Phase 3 studies.

Methods: Pts on stable-dose methotrexate (MTX) from the ORAL Step (NCT00960440; tumor necrosis factor inhibitor-inadequate responder [TNFi-IR] pts) and ORAL Scan (NCT00847613; MTX-IR pts) studies were randomized to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, or placebo (PBO) advanced to either tofacitinib 5 mg BID or 10 mg BID. All PBO pts in ORAL Step advanced at Month 3. In the ORAL Scan study, non-responder PBO pts (<20% reduction from baseline in swollen/tender joint counts) were advanced to tofacitinib 5 or 10 mg BID at Month 3, and all remaining PBO pts were advanced to tofacitinib at Month 6. Non-responding tofacitinib patients remained on the same treatment and dose. Excepting the Health Assessment Questionnaire-Disability Index, the PROs were secondary endpoints and included patient global assessment of disease activity (visual analog scale [VAS]), pain (VAS), health-related quality of life (Medical Outcomes Study Short-Form [36-Item] Health Survey), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue).

Results: In total, 1196 pts received treatment (399 in ORAL Step and 797 in ORAL Scan). Within each study, baseline demographic and disease characteristics were generally similar across treatment groups; differences were noted between studies: ORAL Step pts were required to have failed at least one TNFi and had longer RA disease duration and higher disease activity at baseline relative to pts in ORAL Scan. Treatment with tofacitinib 5 and 10 mg BID resulted in significant improvements in all PROs when compared with PBO (Table 1). Improvements with both tofacitinib doses were observed at 3 months and continued through study end. Based on pts reporting improvements ≥ minimally clinically important differences, numbers needed to treat at Mo 3 for tofacitinib 5 and 10 mg BID, were 3.7-7.8 and 3.1-10.6, respectively, across various PROs in both studies.

Conclusion: In two Phase 3 studies of tofacitinib in combination with MTX, treatment with tofacitinib 5 and 10 mg BID resulted in consistent statistically significant and clinically important improvements in multiple PROs vs PBO.

References:

1.Burmester G et al.  Arthritis Rheum 2011; 63: S279.

2.van der Heijde D et al.  Arthritis Rheum 2011; 63: S107-S108.