JAPAN: Patients with active rheumatoid arthritis (RA) were successfully treated with subcutaneous ozoralizumab at doses of 30 and 80 mg without the addition of methotrexate (MTX), and the results persisted for 52 weeks. Research that was published in Modern Rheumatology showed that the medication had an acceptable tolerability profile over the course of 52 weeks.
RA is a typical autoimmune condition. Despite the fact that the development of tumor necrosis factor (TNF) inhibitors marked a significant advancement in the management of rheumatoid arthritis (RA), conventional anti-TNF antibodies are somewhat immunogenic and their use leads to the development of anti-drug antibodies (ADAs) and loss of efficacy (secondary failure). The trivalent, bispecific NANOBODY® substance ozoralizumab is structurally distinct from IgGs.
Since methotrexate's efficacy and tolerability are insufficient for all rheumatoid arthritis patients, the trial focused solely on ozoralizumab.
With active rheumatoid arthritis, the authors sought to evaluate the effectiveness and safety of a 52-week subcutaneous ozoralizumab treatment at 30 and 80 mg without methotrexate (MTX).
In the open-label, multicenter, phase 3 research (JapicCTI-184031), 140 patients were randomly assigned to receive ozoralizumab 30 mg (n = 94) or 80 mg (n = 46) subcutaneously every four weeks, without MTX, for 52 weeks. Patients who kept taking csDMARDs (conventional synthetic disease-modifying antirheumatic medications), such as MTX, for at least 8 weeks at the visit 4 weeks before starting ozoralizumab treatment, or patients who stopped taking csDMARDs due to safety concerns, were considered eligible. Improvements in the American College of Rheumatology 20/50/70 response rate (ACR20/50/70), Simplified Disease Activity Index (SDAI), and Health Assessment Questionnaire Disability Index (HAD-DI) were among the efficacy endpoints used to measure the treatment's success.
Conclusive points of the trial:
Overall, both cohorts that received ozoralizumab medication showed clinical improvements.
At week 24, both the 30 and 80 mg groups showed high ACR20 response rates (67.0% and 71.7%, respectively), which persisted throughout the research period (72.3% and 78.3%, respectively).
At week 52, post hoc analysis of the 30 and 80 mg groups showed that their respective ACR20 response rates were 58.5% and 65.2%. ACR50/70 also yielded comparable outcomes.
DAS28-CRP and HAQ-DI scores, which were visible as early as week 1 and were sustained through week 52, were two additional endpoints that also showed good improvement.
Efficacy evaluations were comparable for dosages of 30 and 80 mg. The percentage of ozoralizumab-treated patients with SDAI ≤ 3.3 was 19.1% in the 30 mg group and 19.6% in the 80 mg group.
The majority of adverse events were mild to moderate, while 20 patients experienced significant adverse events. When compared to the 30 mg group, adverse events were more common in the 80 mg cohort. However, no specific occurrences were noticed in any of the therapy groups, and no fatalities were reported.
A response generation or rise in anti-ozoralizumab antibodies was seen in 41 (43.6%) of the patients receiving the medication, and 27.7% of the patients in the 30 mg cohort were neutralizing antibody (NAb) positive over the duration of the trial.
The researchers concluded that the proposed method was the first to show that ozoralizumab without MTX (as a monotherapy and in combination with csDMARDs other than MTX) is beneficial and safe in reducing clinical symptoms in a Japanese population.
Reference:
Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. Efficacy and safety of anti-TNF multivalent NANOBODY® compound 'ozoralizumab' without methotrexate co-administration in patients with active rheumatoid arthritis: A 52-week result of phase III, randomised, open-label trial (NATSUZORA trial) [published online ahead of print, 2022 Oct 6]. Mod Rheumatol. 2022;roac126. doi:10.1093/mr/roac126