medwireNews: The next-generation anti-tumor necrosis factor (TNF)-alpha antibody ozoralizumab significantly improves clinical signs and symptoms of rheumatoid arthritis (RA) relative to placebo in people with active disease despite methotrexate therapy, research suggests.
Yoshiya Tanaka (University of Occupational and Environmental Health, Kitakyushu, Japan) and colleagues evaluated the effectiveness of the drug in the phase 2/3 OHZORA trial, which included 381 individuals who had shown an inadequate response to methotrexate monotherapy. They had a mean RA duration of 7.4 years, a baseline DAS28-CRP of 5.13 points, and a baseline mTSS of 27.46 points.
The participants were randomly assigned to receive subcutaneous ozoralizumab 30 mg (n=152), ozoralizumab 80 mg (n=154), or placebo (n=75) every 4 weeks, each given in combination with methotrexate at a mean dose of 10 mg/week.
At week 16, the proportion of patients who met the primary endpoint of an ACR20 response was significantly greater with ozoralizumab 30 mg and 80 mg, at 79.6% and 75.3%, respectively, than with placebo, at 37.3%.
The response was evident from week 1 of treatment and was maintained until week 24, the researchers report in Arthritis & Rheumatology. They also note that there was a similar pattern for ACR50 and ACR70 responses.
There was no significant difference among the three groups in the least-squares mean change in mTSS from baseline to week 24, at 0.6, 0.4, and 0.8 points in the ozoralizumab 30 mg, ozoralizumab 80 mg, and placebo groups, respectively.
However, the proportion of patients with no structural progression at week 24 was significantly greater with ozoralizumab 30 mg and 80 mg (73.0% and 73.4%, respectively) than with placebo (56.0%).
In addition, there were significant differences between the treatment and placebo arms that favored ozoralizumab in a number of other secondary endpoints, including DAS28-CRP, patient’s global assessment of disease activity, patient’s pain assessment, and the Health Assessment Questionnaire Disability Index, with some differences appearing as early as day 3.
Patients in the ozoralizumab 30 mg and 80 mg arms also achieved a significantly higher remission rate (SDAI ≤3.3) than those in the placebo arm, at 25.0% and 23.4% versus 5.3%.
Tanaka and co-authors say that ozoralizumab had “acceptable tolerability with no new safety signals, when compared with other antibodies against tumour necrosis factor alpha.”
Overall, 76.3% of participants in the ozoralizumab 30 mg group, 72.1% of those in the 80 mg group, and 62.7% in the placebo group experienced adverse events (AEs). Serious AEs not leading to death occurred in a corresponding 2.6%, 2.6%, and 2.7% of patients. There was one death, which occurred in the ozoralizumab 80 mg group, as a result of disseminated tuberculosis, and was considered to have a causal relationship with the study drug.
The researchers conclude that as “there was no major difference” in efficacy between the two ozoralizumab doses, “the 30 mg dose was considered to be sufficient for achieving maximal clinical efficacy of ozoralizumab in concomitant therapy with [methotrexate].”
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Arthritis Rheum 2022; doi:10.1002/art.42273