What side effects are associated with this type of intervention?

The most common treatments for Antiphospholipid Syndrome (APS) include anticoagulants like heparin and low-dose aspirin. When considering treatments similar to Certolizumab (an anti-TNF-alpha drug), such as infliximab, known side effects include severe adverse events like CNS lymphoma and Legionella pneumonia, particularly with long-term use. Short-term therapy with infliximab combined with azathioprine has been relatively safe but can lead to drug reactions if used without concomitant immunosuppression. Overall, while anti-TNF-alpha drugs can be effective, they carry risks of serious infections and malignancies.

What prior FDA approvals exist?

Currently, there are no FDA-approved anti-TNF-alpha drugs specifically for the treatment of Antiphospholipid Syndrome (APS). The standard treatment for APS typically includes anticoagulants such as heparin and low-dose aspirin. The trial involving Certolizumab aims to explore the potential benefits of adding an anti-TNF-alpha drug to the usual treatment regimen for pregnant women with APS, but this is still under investigation.

What other types of research exist?

Promising, novel alternatives to Certolizumab for APS patients could include other biologics such as Rituximab (a B-cell depleting agent) and Anifrolumab (an anti-interferon receptor antibody). These drugs have shown efficacy in related autoimmune conditions and may offer new therapeutic options for APS.

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Certolizumab for Pregnancy Complications Due to APS

Q: What is the mechanism of action of this treatment?

Antiphospholipid Syndrome (APS) is commonly treated with anticoagulants like heparin and warfarin, which prevent blood clot formation by inhibiting clotting factors. Low-dose aspirin is also used to reduce platelet aggregation. Certolizumab, an anti-TNF-alpha drug, is being studied for its potential to improve pregnancy outcomes in APS patients. TNF-alpha inhibitors like Certolizumab work by blocking the tumor necrosis factor-alpha, a cytokine involved in systemic inflammation. This is particularly relevant for APS patients as inflammation plays a key role in the pathogenesis of the syndrome, contributing to clot formation and pregnancy complications. By reducing inflammation, anti-TNF-alpha drugs may help mitigate these risks.

Phase 2

Recruiting

Led By D. Ware Branch, MD

Research Sponsored by Ware Branch

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Antiphospholipid syndrome (APS)

Age 18-40 (+364 days) years of age and able to give informed consent

Must not have

Women with urinary excretion with greater than 500 mg (0.5 g) per day (spot urine protein/creatinine ratio 0.5)

Women with a tuberculin skin test induration of 5 mm or greater; or positive quantiFERON-gold test

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 8 weeks gestation through 6-weeks postpartum

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if adding certolizumab to usual treatment can improve pregnancy outcomes in women with APS and LAC. Certolizumab reduces inflammation, which may help improve blood flow to the placenta and lead to better pregnancy results. Certolizumab pegol has been identified as a promising treatment during pregnancy because it has no late active placental transfer and no clear signs of fetal harm.

Who is the study for?

This trial is for pregnant women aged 18-40 with antiphospholipid syndrome (APS) and lupus anticoagulant (LAC), who are less than 8 weeks into their pregnancy. They must have a hematocrit >26% and no history of diabetes, multifetal gestation, certain infections like HIV or tuberculosis, high blood pressure at screening, or be on high doses of prednisone.

What is being tested?

The IMPACT study tests whether adding certolizumab to standard treatment (heparin agent and low-dose aspirin) improves pregnancy outcomes in APS patients with positive LAC tests. All participants receive certolizumab; results will be compared to historical data from similar patients.

What are the potential side effects?

Certolizumab may cause side effects such as infection risks due to immune system suppression, potential allergic reactions, possible heart failure in susceptible individuals, demyelinating disorders like Guillain-Barre syndrome, and could reactivate latent infections like tuberculosis.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with antiphospholipid syndrome.

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I am between 18 and 40 years old and can consent to treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My urine protein levels are high.

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I am a woman with a positive TB skin test or blood test.

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I am a woman taking more than 10 mg of prednisone daily for an autoimmune disorder.

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I have had tuberculosis or a positive TB skin test without treatment.

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I am a woman who is HIV, Hepatitis B, or Hepatitis C positive.

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I need more than 10 mg/day of prednisone for my lupus.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 8 weeks gestation through 6-weeks postpartum

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~8 weeks gestation through 6-weeks postpartum

This trial's timeline: 3 weeks for screening, Varies for treatment, and 8 weeks gestation through 6-weeks postpartum for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Fetal death and/or preterm delivery (<34 weeks) due to PE or PI in women with APS and LAC

Secondary study objectives

Additional adverse outcomes or pertinent concerns, possibly related to study intervention

Side effects data

From 2020 Phase 4 trial • 89 Patients • NCT03020992

17%

Nasopharyngitis

16%

Uveitis

13%

Upper respiratory tract infection

Iridocyclitis

Influenza

Rhinitis

Arthralgia

Alanine aminotransferase increased

Oropharyngeal pain

Prostate cancer

Vestibular disorder

Haemangioma

Pregnancy

Anal polyp

Incarcerated hernia

Cholelithiasis

Sarcoidosis

Pneumonia haemophilus

Pneumonia

Tenosynovitis

Breast cancer

100%

80%

60%

40%

20%

Study treatment Arm

Certolizumab Pegol (SS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Certolizumab PegolExperimental Treatment1 Intervention

All participants are administered certolizumab \[400 mg (given as two subcutaneous injections of 200mg) initially and 2 and 4 weeks later, followed by 200 mg every other week thereafter. 1st dose of certolizumab will be administered by 8 weeks and 6 days gestation and discontinued at 27 weeks 6 days. The regimen of heparin and low dose aspirin is a standard of care treatment for this patient population and is not considered part of the research intervention.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Certolizumab Pegol

2013

Completed Phase 4

~5530

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Antiphospholipid Syndrome (APS) is commonly treated with anticoagulants like heparin and warfarin, which prevent blood clot formation by inhibiting clotting factors. Low-dose aspirin is also used to reduce platelet aggregation. Certolizumab, an anti-TNF-alpha drug, is being studied for its potential to improve pregnancy outcomes in APS patients. TNF-alpha inhibitors like Certolizumab work by blocking the tumor necrosis factor-alpha, a cytokine involved in systemic inflammation. This is particularly relevant for APS patients as inflammation plays a key role in the pathogenesis of the syndrome, contributing to clot formation and pregnancy complications. By reducing inflammation, anti-TNF-alpha drugs may help mitigate these risks.

[Immunosuppressive treatment after kidney transplant: the frontier of chronic antibody-mediated rejection].Intravenous immunoglobulin therapy in rheumatic diseases.