Olokizumab Improves Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis up to 106 Weeks (Results from the Open-Label Extension of Phase III Randomized Clinical Trials).

INTRODUCTION

This analysis evaluated the effects of olokizumab (OKZ) on patient-reported outcomes (PROs) after up to 106 weeks of treatment in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX; MTX-inadequate response [MTX-IR]) or refractory to tumor necrosis factor inhibitor (TNFi; TNFi-inadequate response [TNFi-IR]).

METHODS

Post-hoc analysis was performed of pooled PROs from phase III, double-blind, placebo-controlled trials (CREDO1/2 MTX-IR; CREDO3 TNFi-IR; NCT02760368/ NCT02760407/NCT03225932) and their open-label extension (OLE; up to 106 weeks) in adults with active RA despite treatment with MTX or TNFi. Patients were treated with OKZ 64 mg every 2 weeks (q2w) or every 4 weeks (q4w) + MTX versus MTX + placebo (weeks 0-24) or active comparator (CREDO2), followed by an OLE (all OKZ). The PROs analyzed were patient global assessment; pain (visual analog scale); Health Assessment Questionnaire Disability Index (HAQ-DI); 36-Item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (FACIT-F); Work Productivity Survey Rheumatoid Arthritis (WPS-RA) and the European Quality of Life-Five-Dimension Questionnaire (EQ-5D). Changes from baseline at weeks 12, 24 and 106 were analyzed using a mixed model for repeated measures; analyses included percentages of patients reporting improvements ≥ minimal clinically important difference (MCID).

RESULTS

By week 12, treatment with OKZ compared to placebo (PBO) resulted in greater numerical and clinically meaningfully changes from baseline in all PROs for patients refractory to MTX: the HAQ-DI was - 0.60 for OKZ q2w, - 0.58 for OKZ q4w and - 0.34 for PBO; pain VAS was - 33.26, - 32.51, - 18.39, respectively; and the FACIT-F was 8.47, 8.42 and 4.69, respectively (p < 0.0001). Similar but less prominent improvements were noted in the patients with TNFi-IR. Post hoc analyses demonstrated a higher proportion of patients receiving OKZ reported improvements ≥ MCID versus those receiving PBO (p < 0.05) in all PROs in both groups at week 12. For patients treated with OKZ, the observed improvements from baseline were maintained and increased in magnitude through week 106.

CONCLUSION

Treatment with OKZ over 106 weeks resulted in sustained numerically greater and clinically meaningful improvements in PROs compared to baseline in both RA patients with MTX-IR and those with TNFi-IR. These findings support the long-term benefit of OKZ on PROs.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02760368, NCT02760407, NCT02760433, NCT03120949.