Researchers are reporting favorable long-term results using olokizumab to treat active moderate-to-severe rheumatoid arthritis that has responded inadequately to a commonly used therapy.
The data are drawn from open-label extension (OLE) studies in Western and Asian rheumatoid arthritis (RA) patients who had completed two phase 2 randomized controlled studies testing the use of olokizumab in RA patients on methotrexate who had failed anti-tumor necrosis factor (TNF) therapy.
Olokizumab is an investigational humanized monoclonal antibody that is specific for interleukin-6. Interleukin-6 is a pro-inflammatory cytokine that is involved in multiple immunologic processes that contribute to joint inflammation in RA.
Dr. Mark C. Genovese, co-chief of the Division of Immunology and Rheumatology at Stanford University Medical Center in Palo Alto, CA, presented the findings at the 2015 American College of Rheumatology Annual Meeting.
The analysis included all subjects in the OLE studies who had received at least one dose of olokizumab and had at least one efficacy measurement.
In the two OLE studies, patients received subcutaneous olokizumab 120 mg every 2 weeks plus methotrexate. The protocol for methotrexate use was slightly different in the two studies.
Olokizumab well tolerated, with reductions in disease activity
In RA patients who respond inadequately to disease-modifying anti-rheumatic drugs, TNF inhibitors are often added and usually in combination with methotrexate, Dr. Genovese pointed out. However, nearly half of patients who receive TNF inhibitors also respond inadequately to this treatment.
"The data show that olokizumab was well tolerated, with a safety profile expected for this class of agent, and reductions in disease activity were sustained to week 48," Dr. Genovese observed.
Overall, 36 (18.9%) patients in the OLE study, known as RA0057, and 7 (6.8%) patients in the OLE study, known as RA0089, discontinued treatment due to treatment-emergent adverse events (TEAEs). Throughout the OLEs, TEAEs most often involved infections and infestations.
The efficacy seen with olokizumab in the RCTs was sustained or improved slightly over the longer observation period in the OLE studies.
Specifically, the 48-week mean Disease Activity Score 28 C-reactive protein (DAS28 [CRP]) change from baseline in patients who completed RA0057 was -1.76 in placebo-treated patients and -0.60 in olokizumab-treated patients. In patients who completed the RA0089 study, the mean changes were -2.70 for placebo and -0.68 for olokizumab.
Dr. Genovese said that the results support the continued development of olokizumab for RA. In fact, a phase 3 program known as CREDO (Clinical Rheumatoid Arthritis Development for Olokizumab) is currently in the planning stages.