Background/Purpose: The IMPACT trial (NCT03152058) showed that certolizumab appears effective in preventing placenta-mediated adverse pregnancy outcome (APO) in high-risk antiphospholipid syndrome (APS) patients. We have continued recruitment to this trial and herein summarize our findings.

Methods: We assessed treatment with certolizumab in pregnant patients with APS and LA, administered gestational weeks 8 through 28, in addition to standard treatment with low molecular weight heparin and low dose aspirin. The primary APO was a composite of fetal death >10 weeks’ gestation or preeclampsia with severe features or placental insufficiency requiring delivery < 34 weeks’ gestation. The target sample size for the IMPACT trial was 45 with expected APO rate of 20% with certolizumab versus 40%, the assumed APO rate under the null hypothesis which was considered to be conservative by the study team given the observed APO rate of 44% among IMPACT-eligible patients (ie, with APS and LA) in the PROMISSE Study (N&#3f61). Published results of the IMPACT Trial (Branch et al., Ann Rheum Dis, ePub ahead of print 2025) include data for 45 completed pregnancies. Ongoing recruitment has enrolled 5 additional patients.

Results: In the now completed IMPACT Trial, the pre-determined criteria for efficacy of certolizumab were met. The primary APO rate in the original trial was 20% (9/45 in the modified intention-to-treat population) compared to 40% in historic controls from the PROMISSE Study. With ongoing recruitment, 57 patients have now been enrolled and 56 patients have completed their participation in the trial. Of those enrolled with a prior pregnancy, 87% had a history of an IMPACT primary APO. Baseline characteristics are included in Table 1. Outcomes of prior pregnancies in IMPACT participants are included in Table 2: of 39 previous pregnancies treated with LMWH and LDA that progressed beyond 10 weeks’ gestation 27, (69%) resulted in an IMPACT APO, and only 15 (38%) were liveborn and survived to hospital discharge. Excluding 6 patients that had a pregnancy loss < 10 weeks’ gestation or fetal loss due to genetic abnormalities, outcomes from the certolizumab-treated pregnancy of 50 modified intention-to-treat participants are described below (Table 3). Nine had a primary APO (18.0%; 95% CI: 8.6% - 31.4%), meeting the predetermined criteria for efficacy of certolizumab and significantly lower rates than in historical controls. There were 47 (94%) liveborn infants and all survived to hospital discharge. Median gestational age at delivery was 37 weeks for patients without the primary outcome and 31 weeks for those with the primary outcome. Three patients delivered prematurely (after 34 but before 37 weeks’ gestation) because of placental insufficiency and thus met a secondary outcome. In the trial, there were no serious infections, no substantial increases in antiphospholipid antibodies or other autoantibody levels, and no new cases or severe flares of lupus.

Conclusion: Results of our ongoing enrollment indicate that certolizumab appears effective in preventing placenta-mediated adverse outcomes in high-risk APS patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/certolizumab-pegol-to-prevent-adverse-pregnancy-outcomes-in-patients-with-antiphospholipid-syndrome-and-lupus-anticoagulant-impact-results-from-ongoing-recruitment-of-a-prospective-single-arm-ope/