medwireNews: Olokizumab shows clinical and physical benefits for patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate and tumor necrosis inhibitor (TNF) inhibitor therapy in the latest CREDO findings.
Expanding on the previously reported CREDO1 findings, the phase 3, randomized CREDO2 trial, presented as a poster at the ACR Convergence 2021 virtual meeting, compared the novel humanized monoclonal antibody, which directly targets interleukin (IL)-6, with adalimumab or placebo in patients who had moderate-to-severe disease despite taking methotrexate at a median dose of 17 mg/week.
Roy Fleischmann discusses the implications of the CREDO2 and 3 trial findings looking at olokizumab efficacy versus adalimumab as an add-on to methotrexate and in TNF inhibitor non-responders (3:15).
In all, 943 patients received subcutaneous injections of olokizumab at a dose of 64 mg every 2 or 4 weeks (n=464 and 479, respectively) for 24 weeks in addition to methotrexate. Following 12 weeks of treatment, a respective 70.3% and 71.4% of patients had achieved an ACR20 response.
These rates were similar to the 66.9% rate seen among the 462 patients taking adalimumab 40 mg every 2 weeks and significantly greater than the 44.4% rate for the 243 patients taking placebo.
The same was true for ACR50 and ACR70 responses, “with separation from placebo by week 2,” commented presenting author Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, USA).
Olokizumab was also noninferior to adalimumab and superior to placebo in terms of the proportion of patients with a DAS28-CRP score below 3.2 at 12 weeks, achieved by 45.3% and 45.7% of patients receiving olokizumab at 2- and 4 week-intervals versus 38.3% and 12.8% of those given adalimumab and placebo, respectively. And the IL-6 inhibitor was superior to placebo for HAQ-DI improvement and achieving CDAI remission.
These efficacy outcomes were maintained over the 24 weeks of the trial, during which time the treatment was generally well tolerated. Adverse events were typical for an IL-6 inhibitor with no new safety signals identified.
The overall incidence of treatment-emergent adverse events (TEAEs) was similar across the groups, at 70–70.9% with olokizumab, compared with 65.4% with adalimumab and 63.4% with placebo, and TEAEs led to discontinuation in 4.5–6.3, 5.6%, and 3.7% of patients, respectively.
Infections were the most common TEAEs, seen in a corresponding 30.2–34.0%, 32.0%, and 34.6% of patients, and of these infections 1.3–1.3, 3.5%, and 1.6% were serious.
In the phase 3 CREDO3 trial, also presented as poster at the conference, similar findings were reported by Eugen Feist (Helios Clinic Vogelsang-Gommern, Germany) for olokizumab plus methotrexate when compared with placebo plus methotrexate in RA patients with an incomplete response to TNF inhibitor therapy.
The 299 RA patients randomly assigned to treatment with either the 2-weekly or 4-weekly olokizumab regimen were significantly more likely to achieve an ACR20 response at week 12 than the 69 patients taking placebo, at 60.9% and 59.6% versus 40.6%, respectively.
“At week 24, ACR20 further improved to 58–75%,” with olokizumab, noted Feist.
The treatment was also significantly superior for the secondary endpoints of DAS28-CRP below 3.2 (28–40% vs 12%) and ACR50 response (32–33% vs 16%) at 12 weeks with further reductions at week 24. HAQ-DI score improvement was seen with olokizumab at 12 weeks but the difference compared with placebo was not significant.
Similar to CREDO1 and 2, the overall incidence of TEAEs was 65% with olokizumab versus 51% with placebo. Infections were again the most common TEAEs, seen in a corresponding 25.8–31.6% and 26.1% of patients.
“Importantly, no unexpected safety signals occurred for this IL-6 targeted therapy also with respect to changes in blood cell counts, increase of liver enzymes, and lipid levels over the entire observational period,” said Feist.
“So, I think we can conclude that olokizumab is a new promising drug in the treatment of RA even after failure of TNF inhibitor therapy in this difficult-to-treat population of patients.”
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ACR Convergence 2021; 3–9 November (abstract 1685)
ACR Convergence 2021; 3–9 November (abstract 1686)