Add-on certolizumab in pregnant women with APS Save

Women with antiphospholipid syndrome and lupus anti-coagulant are at high risk of developing adverse pregnancy outcomes (APO). Usual care includes low molecular weight heparin (LMWH) and low dose aspirin (LDA). Despite these therapies, APO have been reported up to 40%. An important question is whether add-on immunosuppressive therapy could improve APO. Studies in animals suggest that TNF is a critical effector of placental dysfunction and foetal death, thus a logical target.

At EULAR 2025 in Barcelona, Dr. Salmon et al. presented data on the efficacy and safety of certolizumab pegol (TNF-i), administered from week 8 through to week 28, as add-on therapy to LMWH + LDA in pregnant women with APS and positive lupus anticoagulant (IMPACT) (OP0273). This was evaluated using single arm, open label, Phase 2 trial. The pre-specified endpoint was 20% or less APO in the treatment arm, based on 40% rate of APO using usual care. Target sample size of 45 patients were achieved. APO was defined as a composite of foetal death ≥10 weeks’ gestation or preeclampsia with severe features or placental insufficiency requiring delivery <34 weeks’ gestation. Using modified intention to treat analysis, primary endpoint was met with 20% of patients with APO. While in the per protocol analysis, the APO rate was 18%.

This finding is clinically relevant. It will be a major challenge to conduct a definitive Phase 3 placebo-controlled RCT in this population. Since these patients are at significant risk of APO, any add-on effective and safe treatment would be most welcomed. If available, I would be in favour of this add on therapy, as well as add-on hydroxychloroquine for added VTE protection. The next step would include extrapolation of use in inflammatory arthritis to APS. Treatment cost should not be a major hurdle as a certolizumab biosimilar may be expected to be approved soon.