Tofacitinib, an oral Janus kinase inhibitor, is approved for the treatment of rheumatoid arthritis (RA). This analysis compared patient-reported outcomes (PROs) from the head-to-head phase 3b/4 trial (ORAL Strategy) of patients with RA and inadequate responses to methotrexate (MTX) who received tofacitinib monotherapy, tofacitinib plus MTX, and adalimumab plus MTX.
The ORAL Strategy trial is a phase 3b/4, 1-year, triple-dummy, active randomized controlled trial that randomized patients 1:1:1 to receive tofacitinib monotherapy (5 mg twice daily), tofacitinib (5 mg twice daily) plus MTX, or subcutaneous adalimumab (40 mg every other week) plus MTX, with MTX dosed at 15 mg to 25 mg per week. Key inclusion criteria included patients ≥18 years of age with active RA despite continuous MTX 15 mg to 25 mg per week for ≥4 months, class I-III functional capacity, ≥4 tender/painful joints and ≥4 swollen joints at baseline, and high-sensitivity C-reactive protein (CRP) ≥3 mg/L. PROs were secondary end points of the trial, and included mean changes from baseline in patient global assessment (PtGA) of disease activity (visual analog scale [VAS]); arthritis pain (VAS); Health Assessment Questionnaire Disability Index (HAQ-DI); 36-Item Short Form Survey (SF-36); EuroQol 5-dimensions questionnaire; Work Productivity and Activity Impairment Questionnaire; Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); and the proportion of patients reporting improvements in HAQ-DI ≥minimum clinically important difference (MCID; –0.22). PROs were assessed at months 6 and 12 using the full analysis set, which included all patients randomized and receiving ≥1 doses of study medication.
A total of 1146 patients were treated on the ORAL Strategy trial (tofacitinib monotherapy, n = 384; tofacitinib plus MTX, n = 376; adalimumab plus MTX, n = 386). Baseline demographics and disease characteristics were comparable among the 3 groups. At months 6 and 12, all treatment groups showed similar mean changes from baseline in HAQ-DI scores as well as improvements ≥MCID. Between the tofacitinib plus MTX and adalimumab plus MTX arms, improvements in all PROs except FACIT-F were similar at months 6 and 12. For FACIT-F, there were significant improvements with tofacitinib combination therapy versus the adalimumab arm at month 6 but not month 12. The PROs relating to PtGA, patient pain, were improved with both combination arms (tofacitinib or adalimumab plus MTX) compared with tofacitinib monotherapy at months 6 and 12. Tofacitinib combination therapy showed improvements in SF-36 at months 6 and 12 versus tofacitinib monotherapy.
These results showed that patients with RA who had an inadequate response to MTX achieved clinically meaningful improvements in PROs with all 3 treatment regimens. PROs were comparable between tofacitinib plus MTX and adalimumab plus MTX therapies, with combination therapy numerically higher than tofacitinib monotherapy.
Strand V, et al. ACR 2017. Abstract 1906.