Ozoralizumab Effectively Treats Active RA Without Methotrexate Co-Therapy

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The study examined ozoralizumab without concomitant therapy, as methotrexate cannot be given to all patients with rheumatoid arthritis due to inadequate efficacy and tolerability.

Treatment with subcutaneous ozoralizumab 30 and 80 mg effectively treated patients with active rheumatoid arthritis (RA) without methotrexate (MTX), which was sustained through 52 weeks. The drug demonstrated an acceptable tolerability profile through the 52-week period, according to a study published in Modern Rheumatology.1

“A phase II/III trial of Japanese patients with active RA with inadequate MTX response revealed that ozoralizumab concomitant with MTX has a rapid reduction of RA symptoms at both 30 mg and 80 mg doses with an acceptable safety profile,” investigators noted. “However, MTX cannot be administered to all patients with RA due to inadequate efficacy and tolerability.”

The open-label, multicenter, phase 3 study (JapicCTI-184031), conducted between October 2018 and October 2020 at 30 sites in Japan, randomized 140 patients 2:1 to receive subcutaneous ozoralizumab 30 (n = 94) or 80 mg (n = 46) every 4 weeks, without MTX, for 52 weeks. Eligible patients had active RA and included either patients who continued conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), including MTX, for at least 8 weeks at the visit 4 weeks prior to beginning ozoralizumab treatment, or those who discontinued csDMARDs for safety concerns.

Efficacy endpoints included the Disease Activity Score 28 (DAS28-CRP), a patient’s pain assessment (Pt-PA), 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).

Overall, ozoralizumab treatment demonstrated clinical improvements among both cohorts. The ACR20 response rates were high in both the 30 and 80 mg groups at week 24 (67.0% and 71.7%, respectively), which were maintained through the study period (72.3% and 78.3%, respectively). Post hoc analysis of the 30 and 80 mg groups indicated an ACR20 response rate at week 52 of 58.5% and 65.2%, respectively. Similar results were shown for ACR50/70 as well.

Supplementary endpoints also reported good improvement, including DAS28-CRP and HAQ-DI scores, which were seen as early as week 1, and were maintained through week 52. Efficacy assessments were comparable between both 30 and 80 mg doses. The proportion of patients receiving ozoralizumab achieving SDAI ≤3.3 were 19.1% in the 30 mg group and 19.6% in the 80 mg group.

The majority of adverse events were categorized as mild to moderate, with serious adverse events occurring in 20 patients. Adverse events were higher in the 80 mg cohort when compared with the 30 mg group. However, no specific events were observed across treatment arms and there were no deaths reported.

An anti-ozoralizumab antibody response generation or increase was observed in 41 (43.6%) patients receiving the drug, and 27.7% of those in the 30 mg cohort were neutralizing antibody (NAb) positive throughout the trial period.

Exclusively including Japanese patients with inadequate response or intolerance to DMARDs limits the study. Further, the unique genetic, medical, and environmental background of these patients may impact safety and efficacy of biological agents in patients with RA. Lastly, the small sample size and inclusion and exclusion criteria, which included disease activity, was not designed as a placebo-controlled or active-controlled trial.

“This is the first trial to demonstrate that ozoralizumab without MTX (as a monotherapy and in combination with csDMARDs except for MTX) is effective in improving clinical symptoms in a Japanese population, as well as the safety of ozoralizumab in this population,” investigators concluded.


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