In the framework of the annual ACR Convergence 2021, R-Pharm Group presented successful results of olokizumab in two randomized clinical trials of phase III global research program — CREDO (Clinical RhEumatoid Arthritis Development of Olokizumab) – CREDO 2 and CREDO 3.
In CREDO 2, the primary endpoint ACR20 response rate at week 12 was achieved in 326 subjects (70.3%) with olokizumab every two weeks, 342 (71.4%) – with olokizumab every four weeks, 309 (66.9%) with adalimumab and 108 (44.4%) in the placebo group. The statistical significance of these results was high (p<0.0001). In CREDO 3, ACR20 response rates were 60.9% in olokizumab every two weeks, 59.6% in olokizumab every four weeks and 40.6% in placebo (p<0.01 for both comparisons). There were significant differences in achievement of Disease Activity Score 28-joint count C-reactive protein <3.2 between olokizumab-treated arms and placebo. The improvements in efficacy and patient reported outcomes were maintained throughout 24-weeks and noted after Week 16 in patients who switched from placebo.
Olokizumab, in combination with methotrexate, has shown effect even in cases where conventional treatment or TNF-α inhibitors demonstrate no clinical improvement. No new safety signals were observed, other than what is expected of IL-6 inhibitor class.
CREDO 2 results were presented by Professor Roy M. Fleischmann of the Metroplex Clinical Research Center in Dallas (USA). Treatment with olokizumab was associated with significant improvements in clinical manifestations and physical function in RA patients compared to placebo and non-inferior to adalimumab. In all groups, patients received treatment in combination with methotrexate. Olokizumab was effective in both regimens: injections every 2 and every 4 weeks, which allows to select a more convenient therapy.
Safety and efficacy of olokizumab were already stated and proven for methotrexate nonresponders. Eugen Feist (Germany) shared CREDO 3 clinical trial results, which focused on the TNF incomplete responders. He drew attention to the clinically significant improvement shown by the study from the second week of therapy: patients noted a decrease in pain levels, function and global assessment of the disease (evaluated with visual analog scale).
During the Satellite Symposium*, the leading rheumatologists discussed benefits and features of olokizumab, focused on its new therapeutic possibilities and shared efficacy and safety profile of olokizumab during poster presentations. Important olokizumab characteristics included reaching the desired outcome of reducing inflammation with less frequent dosing. Additionally, targeting the IL-6 cytokine may further close the gap to optimal responses in a treat-to-target strategy.
*The symposium was not part of the ACR scientific program
The rationale for olokizumab development and large clinical trials was the growing number of patients with rheumatoid arthritis worldwide and lack of effective treatment with existing drugs in some patient categories. Olokizumab is the first approved monoclonal antibody for RA that binds with IL-6 directly, unlike other drugs in IL-6 inhibitor class that target the IL-6 receptor. It is of substantial scientific and clinical interest to explore whether this mechanism of action could differentiate efficacy and safety outcomes in RA, and, potentially, in other conditions.