Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

Abstract

Objective: To evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).

Methods: In this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.

Results: A total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.

Conclusions: Treatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed. Trial registration number NCT02760368.

Keywords: antirheumatic agents; arthritis; cytokines; rheumatoid.

Figure 1

Gate-keeping strategy. p_{Sup, q2w} and p_{Sup, q4w} represent p values from a one-sided test of superiority versus placebo for OKZ dose regimens 64 mg q2w and q4w. ACR, American College of Rheumatology response; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score 28 based on C reactive protein; HAQ-DI, Health Assessment Questionnaire Disability Index; OKZ, olokizumab; q2w, every 2 weeks; q4w, every 4 weeks; Wk, week.

Figure 2

Patient disposition. AE, adverse event; IC, informed consent; ITT, intention-to-treat; MTX, methotrexate; OKZ, olokizumab; OLE, open-label extension; PBO, placebo; q2w, every 2 weeks; q4w, every 4 weeks.

Figure 3

Efficacy results during the double‐blind treatment period (ITT population). ACR, American College of Rheumatology response; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score 28 based on C reactive protein; HAQ-DI, Health Assessment Questionnaire Disability Index; ITT, intention-to-treat; OKZ, olokizumab; PBO, placebo; q2w, every 2 weeks; q4w, every 4 weeks.

Figure 4

Mean changes in laboratory values during the double‐blind treatment period (safety population). HDL, high-density lipoproteins; LDL, low-density lipoproteins; OKZ, olokizumab; PBO, placebo; q2w, every 2 weeks; q4w, every 4 weeks.