Background: Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 ^{1, 2}. Here we present the results of the first phase III study of OKZ in patients with Rheumatoid Arthritis (RA).

Objectives: The primary objective was to evaluate the safety and efficacy of OKZ administered subcutaneously (SC) every 2 weeks (q2w) and 64mg SC every 4 weeks (q4w) vs placebo in the treatment moderate-to-severe RA.

Methods: In this randomized, double-blind, placebo-controlled, multicenter study in patients with moderately to severely active RA despite methotrexate (MTX) (ClinicalTrials.gov Identifier NCT02760368, CREDO-1) patients received SC injections of OKZ 64 mg q2w, OKZ 64 mg q4w and PBO q2w for 24 weeks. Starting at Week (Wk) 14, non-responders were rescued. After Wk 24, subjects were eligible for an open-label study extension.

The primary endpoint was American College of Rheumatology 20% (ACR20) response at Wk 12.

Secondary endpoints included: percentage of subjects with low disease activity, improvement of physical ability. Safety outcomes, including treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) and laboratory abnormalities (via central lab) were assessed.

Results: 428 patients were randomized to OKZ 64mg q2w (n=143), OKZ 64mg q4w (n=142), and PBO (n=143). Baseline characteristics were comparable between treatment arms: mean (SD) age was 51.3 (12.0) years, 82.7% of patients were female, disease duration 8.14 (7.6) and all patients were on MTX. Mean (SD) baseline DAS28-CRP was 6.0 (0.76) and HAQ-DI was 1.72 (0.49).

130 (90.9%) patients in q2w, 134 (94.4%) in q4w and 132 (92.3%) in PBO arms completed the study.

Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints (Table 1).

The key efficacy outcomes were maintained throughout the 24-week.

Overall incidence of TEAEs was 58.0% in OKZ q2w arm; 57.0% in OKZ q4w arm and 43.7% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.9%, 3.5% and 0.7% patients, respectively.

At least one TESAE (subcutaneous abscess, pulmonary tuberculosis, staphylococcal sepsis, toxic shock syndrome, cervix carcinoma, obstructive pancreatitis, diabetic vascular disorder) was reported in 8 (5.6%) of OKZ groups, numerically higher than 4(2.8%) in PBO. There was one death due to septic shock in the OKZ q2w arm.

Conclusion: Treatment with OKZ over a 24-week period was associated with significant improvements in the signs, symptoms and physical function of RA, with a safety profile consistent with Phase II data for OKZ and with the data for the agents with similar mechanism of action.

There were no discernible differences between the two regimens of OKZ in efficacy or safety outcomes.

References: [1]Genovese MC et al. Ann Rheum Dis. 2014 Sep; 73:1607; 2. Takeuchi T, et al. Mod Rheumatol. 2016; 26:1

Acknowledgments: Investigators and patients of CREDO-1 study.

Disclosure of Interests: Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm, Rumen Stoilov Grant/research support from: R-Pharm, Tamara Tyabut: None declared, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme