Olokizumab superior to placebo, noninferior to adalimumab for rheumatoid arthritis

Olokizumab was superior to placebo and noninferior to adalimumab in achieving ACR20 response* among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate maintenance therapy, according to the CREDO2** study.

This phase III, multicentre, double-blind, placebo- and active-comparator-controlled trial involved 1,648 patients with RA. Participants were randomly assigned to receive subcutaneous injection of olokizumab 64 mg either Q2W (n=464, mean age 53.3 years) or Q4W (n=479, mean age 53.7 years), adalimumab 40 mg Q2W (n=462, mean age 54.3 years), or placebo Q2W (n=243, mean age 54.7 years) in addition to methotrexate for 24 weeks. The primary endpoint of the study was an ACR20 response at week 12 between the olokizumab and placebo groups. [N Engl J Med 2022;387:715-726]

Olokizumab vs placebo

At week 12, both olokizumab regimens were superior to placebo in achieving ACR20 response (70.3 percent [Q2W] and 71.4 percent [Q4W] vs 44.4 percent; adjusted difference, 25.9 and 27.0 percentage points, respectively; p<0.001 for both).

More patients treated with olokizumab achieved DAS28-CRP*** level of <3.2, which indicates less disease activity, compared with those receiving placebo (45.3 percent [Q2W] and 45.7 percent [Q4W] vs 12.8 percent; adjusted difference, 32.5 and 32.9 percentage points, respectively; p<0.001 for both).

Improvement in physical function was greater with olokizumab than placebo, as reflected by the reductions in HAQ-DI⁺ score from baseline to week 12 (-0.64 [Q2W] and –0.61 [Q4W] vs -0.42).

At week 24, more patients on olokizumab also achieved ACR50⁺⁺ response (50.4 percent [Q2W]) and 50.1 percent [Q4W] vs 22.6 percent) and CDAI⁺⁺⁺ score of ≤2.8, which indicates remission (11.2 [Q2W] and 12.1 percent [Q4W] vs 4.1 percent) than those on placebo.

Olokizumab vs adalimumab

Olokizumab demonstrated noninferiority over adalimumab in terms of the percentage of patients with an ACR20 response at week 12 (70.3 percent [Q2W] and 71.4 percent [Q4W] vs 66.9 percent; difference, 3.4 and 4.5 percentage points; p<0.001 for both).

All other secondary endpoints, such as DAS28-CRP of <3.2, change in HAQ-DI score, ACR50 response, and CDAI score of ≤2.8, were similar between the olokizumab and the adalimumab groups.

Overall safety

The most common adverse event reported was infection, which occurred in 30.2, 34.0, 32.0, and 34.6 percent of participants in the respective olokizumab Q2W, olokizumab Q4W, adalimumab, and placebo groups. Nonetheless, the event was generally mild to moderate in severity as assessed by the investigators.

“In patients with RA who were receiving maintenance methotrexate, … treatment with olokizumab resulted in a higher percentage of patients with an ACR20 response over a 12-week period than placebo, and olokizumab was noninferior to adalimumab,” said the researchers.

“[This] trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure … [Hence,] longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with RA,” they suggested.

*ACR20 response: American College of Rheumatology 20 response, defined as ≥20 percent decrease in tender- and swollen-joint counts and ≥20 percent improvement in at least three of five other domains, such as patient’s assessment of disease activity and pain, physician’s assessment of disease activity, patient function, and assessment of C-reactive protein level

**CREDO2: Evaluation of the efficacy and safety of two dosing regimens of olokizumab (OKZ), compared to placebo and adalimumab, in subjects with rheumatoid arthritis (RA) who are taking methotrexate but have active disease

***DAS28-CRP: Disease Activity Score for 28 joints based on the CRP

⁺HAQ-DI: Health Assessment Questionnaire-Disability Index

⁺⁺ACR50: ≥50 decrease in both the tender- and swollen-joint counts and ≥50 percent improvement in at least three of five other domains

⁺⁺⁺CDAI: Clinical Disease Activity Index