Olokizumab improves patient reported outcomes in moderate to severely active rheumatoid arthritis patients inadequately controlled by methotrexate (MTX-IR): results from phase 3 randomized controlled trial, CREDO 2
Olokizumab (OKZ) is an interleukin-6-inhibitor for the treatment of Rheumatoid Arthritis (RA). The analysis presents patient reported outcomes (PROs) from MTX-IR patients with moderate to severely active RA treated with OKZ vs adalimumab (ADA) or placebo in a phase 3 randomized controlled trial (RCT) (ClinicalTrials.gov number, NCT02760407).
The objectives were to assess the effect of OKZ treatment compared with placebo and ADA in patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), fatigue (FACIT-F) and health related quality of life, as well as work participation (WPS-RA) at week 12.
The research involved 1648 patients receiving MTX, who were randomized to receive SQ injections: 1) OKZ 64 mg every 2 weeks (q2w, n=464), 2) OKZ 64 mg q4w (n=479), 3) ADA 40 mg q2w (n=462), and 4) placebo q2w (n=243). At week 14, non-responders, i. e. subjects who did not show ≥ 20% improvements in both swollen and tender joint counts, started receiving rescue medication (sulfasalazine and/or hydroxychloroquine) in addition to the therapy under examination. The authors analyses differences between the groups in least-squares mean (LSM) changes from the baseline.
At week 12, treatment with both OKZ doses and ADA resulted in statistically greater LSM changes from baseline than placebo across all PROs, including 7 of 8 domains of SF-36 (with exception of role emotional). Patients reported improvements, with work and household work impairments; household work days missed because of arthritis improved (p<0.01) with OKZ and ADA treatment. PROs went on improving up to week 24 in the active treatment arms. Post hoc analyses demonstrated that a higher proportion of patients receiving both doses of OKZ as well as ADA reported improvements that were more significant than minimum clinically important differences vs placebo (p<0.01) across all PROs, indicating clinically meaningful benefits on an individual patient basis. Estimates of NNT indicated that between 5 and 10 patients would need to be treated to achieve these benefits. More patients in both OKZ groups reported scores exceeding normative values in PtGA, HAQ-DI and SF-36 PCS scores; in the case of the ADA, such improvement was found in PtGA and HAQ-DI.
In conclusion, it is stated that treatment with both doses of OKZ resulted in similar, statistically significant improvements across PROs vs placebo in MTX-IR patients with moderate to severely active RA, comparable to ADA, that were clinically meaningful.
The study was founded by R-Pharm, which also contributed to its design, participated in data collection, analysis, and interpretation, as well as in abstract writing, review, and approval. No honoraria or payments were made for authorship.
