Impact of anti-drug antibodies and neutralising antibodies on safety and efficacy of ozoralizumab in rheumatoid arthritis.
Masafumi Kawanishi, Tsutomu Takeuchi, Nobuko Horiuchi et al.
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In 30 seconds
This analysis of participants in the phase II/III OHZORA trial (ozoralizumab with methotrexate) and phase III NATSUZORA trial (without methotrexate) assessed antidrug antibodies (ADAs), neutralising antibodies (NAbs), and clinical outcomes in rheumatoid arthritis. ADAs occurred in 29.2% and 44.3% of participants, respectively; NAbs occurred in 7.5% and 19.3%. ADA induction was not associated with treatment continuation or safety. NAb-positive participants had reduced efficacy in NATSUZORA, but not significantly in OHZORA, where methotrexate was co-administered.
Key findings
- ADA induction occurred in 29.2% of OHZORA participants and 44.3% of NATSUZORA participants.
- NAb expression occurred in 7.5% of OHZORA participants and 19.3% of NATSUZORA participants.
- ADA induction was not associated with treatment continuation or safety.
- NAb-positive participants in NATSUZORA had reduced efficacy, while approximately half maintained low disease activity through week 52; no significant efficacy impact was seen in OHZORA.
Why it matters
Antibody development may affect biologic treatment response, but these trial analyses suggest that its clinical impact varies by treatment context. The lower NAb frequency and lack of a significant efficacy impact in the methotrexate co-treatment trial are consistent with a possible role for methotrexate in preserving response, although the findings do not establish that it prevents antibody development.
What to keep in mind
The findings come from subgroup comparisons across two trials with different methotrexate use, so differences between trials cannot be attributed to methotrexate alone.