CREDO 1: Novel biologic for rheumatoid arthritis hits mark

Treatment with olokizumab yields significant improvements in signs and symptoms of rheumatoid arthritis (RA), particularly among patients with active disease despite receipt of an adequate dose of methotrexate, according to the results of the phase III CREDO 1 trial.

Moreover, the drug confers benefits for disability and quality of life measures with no unexpected safety findings, the investigators said. The onset of efficacy is apparent within 2 weeks from the start of treatment.

CREDO 1 randomized 428 RA patients (average age 51 years, 83 percent female) to receive subcutaneous injections of olokizumab 64 mg either every 2 weeks (n=143) or every 4 weeks (n=142) or placebo (n=143) in addition to methotrexate for 24 weeks. Baseline demographic and disease characteristics were well balanced across the three treatment groups.

At week 12, the primary endpoint of an American College of Rheumatology 20 percent (ACR20) response occurred with significantly greater frequently in the active treatment groups than in the placebo group (63.6 percent and 70.4 percent with olokizumab every 2 and 4 weeks, respectively, vs 25.9 percent; p<0.0001 for both comparisons). The difference was seen starting around week 2 and plateaued at week 12. [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2021-219876]

Likewise, olokizumab showed superiority over placebo in terms of secondary efficacy endpoints. About one-third of patients in both active treatment groups achieved Disease Activity Score 28-joint count based on C reactive protein <3.2 (DAS28-CRP <3.2; 33.6 percent and 38.7 percent with the every-2-weeks and every-4-weeks regimens, respectively) relative to only 3.5 percent of those on placebo (p<0.0001 for both comparisons).

The Health Assessment Questionnaire Disability Index (HAQ-DI) scores increased by 0.54, 0.56, and 0.20 with the every-4-weeks regimen, every-2-weeks regimen, and placebo, respectively (p<0.0001 for both comparisons). Meanwhile, the ACR50 response at week 24 was documented in 48.6 percent, 42.7 percent, and 7.7 percent, respectively (p<0.0001 for all comparisons).

“Chronic arthritis can have a profound effect on patients’ quality of life,” the investigators noted. “In this study it was shown that the improvements seen in signs and symptoms and disability of RA were mirrored by positive effects on quality of life measures, including Short Form-36 (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F).”

In RA, it is possible that certain mental ailments such as sleep disorders and fatigue may contribute to high levels of circulating interleukin (IL)-6, as the investigators pointed out. “Olokizumab treatment resulted in marked improvements in fatigue, consistent with its mechanism of action as an inhibitor of IL-6.”

With regard to safety, the findings confirmed that olokizumab has a safety profile similar to approved anti-IL-6R antagonists and no unexpected safety findings. [RMD Open 2019;5:e000887; Ther Clin Risk Manag 2010;6:143-152]

“As expected, there were more adverse events observed in the olokizumab-treated patients, but they were mostly mild to moderate with few serious adverse events … and relatively low number of dropouts due to an adverse event,” the investigators noted, adding that none of the patients developed neutralizing antidrug antibodies.

Overall, CREDO 1 provides meaningful controlled data on the efficacy and safety of olokizumab in a population of patients with inadequate response to methotrexate, according to the investigators. This will prove to be useful to clinicians who might want to use the drug in their practice once it is approved.

Olokizumab has already been approved for use in Russia.