Impact of Anti-Drug Antibodies and Neutralising Antibodies on Safety and Efficacy of Ozoralizumab in Rheumatoid Arthritis

Objectives To evaluate the induction of antidrug antibodies (ADA) and the expression of neutralising antibodies (NAb) during ozoralizumab treatment, a trivalent anti-TNFα NANOBODY® compound for rheumatoid arthritis, and their impact on safety and efficacy. Methods Data from a phase II/III trial of ozoralizumab co-administered with methotrexate (OHZORA) and a phase III trial without methotrexate (NATSUZORA) were analysed. Participants were stratified by ADA and NAb status. Safety and efficacy outcomes were compared across subgroups. Results ADA induction was observed in 29.2% (OHZORA) and 44.3% (NATSUZORA) of participants; NAb expression was observed in 7.5% and 19.3%, respectively. ADA induction was not associated with treatment continuation or safety. In NATSUZORA, reduced efficacy was observed in the NAb-positive participants, although approximately half of those participants maintained low disease activity through Week 52. In OHZORA, NAb expression showed no significant impact on efficacy. Several NAb-positive participants in either trial showed sustained disease control in the long-term extension (HOSHIZORA). Conclusions ADA induction had no apparent impact on safety. The effect of NAb expression on efficacy was limited particularly in OHZORA, suggesting that methotrexate co-administration may reduce NAb development and contribute to the optimal preservation of efficacy and safety in clinical practice.