LAS VEGAS — Updated results of a small, open-label phase 2 study of certolizumab pegol in pregnant women with antiphospholipid syndrome (APS), including those with systemic lupus erythematosus (SLE), continue to show that the TNF-alpha inhibitor can significantly reduce the rate of adverse pregnancy outcomes (APOs).

The results from the trial, called IMPACT, which were first published in 2025 and reported by Medscape Medical News, showed that certolizumab was associated with more than a 50% reduction in APOs when compared with historical control individuals, according to the trial’s co-primary investigator, Jane E. Salmon, MD.

Certolizumab, which does not cross the placenta, received a Breakthrough Therapy Designation from the FDA last month for the prevention of placenta-mediated APOs in pregnant women who have APS and are positive for lupus anticoagulant (LA).

At Perspectives in Rheumatic Diseases (PRD) 2026, Salmon, rheumatologist affiliated with Hospital for Special Surgery and professor of both medicine and obstetrics at Weill Cornell Medicine in New York City, said that even though certolizumab has not yet gained a new indication for the prevention of placenta-mediated APOs, the data already have clinical relevance, particularly in the context of the highly limited benefits of standard approaches.

Salmon encouraged close monitoring of high-risk patients in settings such as future clinical trials of certolizumab, noting that IMPACT is still enrolling patients for safety and biomarker data.

“We should not protect at-risk pregnant women from research; we should protect them through research,” she said.

Details of the IMPACT Trial

In IMPACT, patients were 18-40 years old, had clinically diagnosed APS, and tested positive for LA on two or more occasions more than 12 weeks apart within the previous 18 months. They received standard doses of certolizumab on top of a standard guideline-recommended therapy with low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA). The trial’s composite primary endpoint combined the rates of otherwise unexplained fetal death at ≥ 10 weeks of gestation and preeclampsia or placental insufficiency requiring delivery at < 34 weeks of gestation.

The IMPACT results published in 2025 reported on 51 patients, of whom 45 completed 10 weeks of gestation, which was the criterion for inclusion in the final modified intention-to-treat analysis. At that time, 42 (93%) of the 45 pregnancies had live births with infants surviving to hospital discharge and seven pregnancies developed preeclampsia or placental insufficiency requiring delivery at < 34 weeks of gestation; one patient experienced both outcomes in her pregnancy.

Since the 2025 publication, Salmon said that 10 more pregnancies have been added, all of which ended in a child leaving the hospital alive, giving an overall rate of survival to hospital discharge of 95%.

Although IMPACT was uncontrolled, the reduction of APOs was remarkable compared with historical comparisons. In one of two such comparisons, pregnancies in IMPACT were found to be substantially lower APO rates than those in the PROMISSE study published in 2012. PROMISSE provided some of the groundwork for IMPACT by evaluating risk factors for APOs in women with antiphospholipid antibodies, SLE, or both.

The APO rate was 44% among 59 patients in the PROMISSE study who would have met the enrollment criteria for IMPACT compared with 20% (9 of 45 pregnancies) in those who were assigned to receive certolizumab in IMPACT. The APO rate was 37% in historical control individuals from PROMISSE who were receiving LMWH plus LDA.

Another set of historical control individuals for comparison came from IMPACT itself. Investigators paired pregnancy outcomes in the IMPACT participants with those from their most recent prior pregnancy that survived at least 10 weeks. Most prior pregnancies were managed with the standard of LMWH and LDA, with the remaining patients also receiving hydroxychloroquine.

Of the 24 pairs, pregnancies managed in IMPACT had a significantly longer gestation (36.5 vs 24.0 weeks; P < .001) and a significantly lower rate of APOs (21% vs 79%; P < .001), Salmon reported.

The rate of fetal demise was more than 80% lower (12% vs 65%; P < .001), she added.

Despite concerns that an anti-inflammatory agent might impair immune function in a patient population with an autoimmune disease, no serious adverse events were associated with certolizumab in IMPACT, according to Salmon.

Although two patients (both without SLE) became seropositive for anti-double-stranded DNA antibodies, there were no clinical manifestations associated with the change. There were no flares definitely attributed to SLE. There were also no changes in anticardiolipin or anti-beta₂ glycoprotein I immunoglobulin G antibodies observed.

Inflammation Joins Thrombosis as Pregnancy Risk

IMPACT’s results do not rule out the value of the standard antithrombotic therapies of LMWH and LDA for pregnancy in women with APS as recommended in the 2020 American College of Rheumatology (ACR) guideline on the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases, which has not yet been updated. Rather, they support the hypothesis that inflammation might be another target, said Bonnie Bermas, MD, clinical director of the Division of Rheumatic Diseases at the University of Texas Southwestern Medical Center in Dallas.

“While the trial was small, single-armed, and relied on historical controls, the results are impressive and suggest that persons with SLE and antiphospholipid syndrome may benefit from both anticoagulation and directed therapy against inflammation,” said Bermas, who was not involved in the IMPACT trial.

“Importantly, the findings suggest that inflammation as well as thrombosis is an important driver for pregnancy loss in these patients,” added Bermas, co-author of the 2020 ACR guideline.

Noting that “obstetrical APS with or without SLE can be a management challenge and devastating for patients,” Bermas indicated that further studies confirming the IMPACT results might provide a meaningful advance.

The Lupus Foundation of America (LFA) provided a similar interpretation of the IMPACT study in a statement. Attributing APS with a 10-fold increase in the risk for pregnancy complications, the LFA expressed excitement about the IMPACT results and said new treatment options are “desperately needed.”

By addressing the inflammatory response, the IMPACT trial “has the potential to provide a new approach,” the statement reads, singling out certolizumab as a candidate for becoming “the first biologic that may help prevent pregnancy complications” in SLE and APS, as well as in other diseases in which inflammation threatens pregnancy outcomes.

The IMPACT trial was supported by funding from the National Institutes of Health, the LFA, the Morris and Alma Schapiro Fund, the James R. and Jo Scott Research Endowment at the University of Utah, and UCB, which markets certolizumab. Salmon reported financial relationships with Abbott, Biogen, Bristol Myers Squibb, Johnson & Johnson, Eli Lilly and Company, Merck, Pfizer, Regeneron, UCB, and Zimmer Biomet. Bermas reported no potential conflicts of interest.

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including rheumatology, for several decades.