Olokizumab bests placebo, noninferior to adalimumab in RA with methotrexate
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Olokizumab demonstrated superiority compared with placebo and non-inferiority compared with adalimumab in patients with rheumatoid arthritis who were receiving methotrexate as a maintenance therapy, according to data.
“Monotherapy with adalimumab is not standard therapy for rheumatoid arthritis because the combination of adalimumab and methotrexate has been shown to be superior to monotherapy,” Josef F. Smolen, MD, from the division of rheumatology at the Medical University of Vienna, and co-authors wrote in the New England Journal of Medicine. “In this trial, we evaluated the efficacy and safety of subcutaneous olokizumab in the treatment of rheumatoid arthritis.”
To investigate the safety and efficacy of subcutaneous olokizumab (UCB) in patients with RA who are also receiving MTX, compared with placebo and adalimumab (Humira, AbbVie), the authors conducted a phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator controlled trial. The trial was conducted from May 2016 through November 2019, at 209 sites in the U.S., U.K., continental Europe, South Korea, Taiwan and Latin America, the authors wrote.
Patients were randomized at 2:2:2:1, and received, respectively, subcutaneous injections of olokizumab 64 mg every 2 weeks, subcutaneous injections of olokizumab 64 mg every 4 weeks, adalimumab 40 mg every 2 weeks or a placebo every 2 weeks. Dosing went on for 24 weeks. After 24 weeks, patients were invited to participate in a 20-week follow-up period to further investigate safety outcomes.
To be included, patients were required to be aged 18 years or older and have active RA that satisfied the American College of Rheumatology-EULAR 2010 revised classification criteria. Additionally, included patients demonstrated a subpar response to MTX when receiving 15 mg to 25 mg of the therapy for at least 12 weeks.
Patients who did not achieve a response of ACR20 at week 14 of the trial were prescribed rescue medication. The primary efficacy endpoint for the study was an ACR20 or greater improvement by week 12. Secondary endpoints were ranked and multiplicity controlled, and included noninferiority of each olokizumab dose to adalimumab regarding the ACR20 response at week 12, the percentage of patients with a DAS28 based on C-reactive protein levels of less than 3.2 at week 12, decreases in the Health Assessment Questionnaire-Disability Index score from baseline to week 12, ACR50 responses at week 24 and a Clinical Disease Activity Index score of 2.8 or less at week 24, the authors wrote.
Additionally, investigators monitored and assessed adverse events that began or worsened in severity following the first dose of the trial. Special interest adverse events included “serious infections, systemic injection reactions, cancers, autoimmune disorders, gastrointestinal perforations, elevation of lipid levels, cytopenia, demyelination in the peripheral or central nervous system, potential hepatotoxic effects, and adjudicated MACE.”
In total, the trial included 1,643 patients, of which 464 received olokizumab every 2 weeks, 479 who received olokizumab every 4 weeks, 462 who received adalimumab and 243 who received placebo therapy. Overall, 44% of patients receiving placebo therapy achieved ACR20 responses at week 12. In contrast, 70.3% of patients receiving olokizumab every 2 weeks achieved an ACR20 response (Difference vs. placebo = 25.9; 97.5% CI, 17.1-34.1).
In patients receiving olokizumab every 4 weeks, 71.4% achieved an ACR20 response (difference vs. placebo = 27 percentage points; 97.5% CI, 18.3-35.2). Among patients receiving adalimumab, 66.9% achieved an ACR20 response (difference vs. placebo = 22.5 percentage points; 95% CI, 14.8-29.8). Adverse events consisted mainly of “common infections” and occurred in roughly 70% of patients, the authors wrote.
“In this trial involving patients with rheumatoid arthritis, olokizumab plus methotrexate was superior to placebo plus methotrexate with respect to an ACR20 response at week 12 and was noninferior to the combination of adalimumab and methotrexate,” Smolen and colleagues wrote. “Olokizumab was also superior to placebo with respect to an ACR50 response (secondary endpoint).”
- References:
- Breedveld FC, et al. Arthritis Rheum. 2006;doi: 10.1002/art.21519
- Fraenkel L, et al. Arthritis Rheumatol. 2021;doi:10.1002/art.41752
- Smolen JS, et al. Ann Rheum Dis. 2020;doi: 10.1136/annrheumdis-2019-216655
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