Antiphospholipid syndrome management rife with theoretical, imperfect therapies
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Preventing a first clotting event with aspirin may be the only truly effective treatment option in antiphospholipid syndrome, according to a presenter at the 2021 Congress of Clinical Rheumatology-East.
“The biggest challenge is primary prevention,” Richard Furie, MD, chief of the division of rheumatology at Northwell Health, and professor of medicine at Hofstra/Northwell School of Medicine in New York, told attendees.
But Furie stressed that APS has proven a challenging area for therapeutic development, largely because the event rate is so low. “We don’t even know about the epidemiology or how prevalent this disease is,” he said.
With that in mind, Furie provided an all-comers overview of the various treatments that have been used or studied in APS, starting with primary prevention strategies and finishing with a pipeline update.
The first step in primary prevention is identifying patients with the three most common antibodies in APS. Those are the lupus anticoagulant (LAC), IgG/IgM anti-beta2 glycoprotein I (2GPI) and IgG/IgM anticardiolipin (aCL), according to Furie. “IgG has gotten more credit than IgM,” Furie said. “We don’t know what to do with IgA, but I think IgA counts for a lot.”
So-called triple positivity of those antibodies is a key predictor of thrombotic risk. However, Furie believes that it is not just the presence of these antibodies that of most concern. “The titer of APS antibodies is important,” he said. “But this is just my own opinion.”
Other predictive factors, according to the Global APS Score (GAPSS) include hyperlipidemia and arterial hypertension.
Furie then discussed what to do once these patients have been identified. He raised questions about the utility of aspirin as a primary prevention measure. “Most of us are giving baby aspirin but are we treating the patient or treating ourselves?” he said.
A treatment goal of international normalized ratio (INR) of 3.0 may be easier to reach with warfarin, but it is still not easy, according to Furie. “It is a pain in the neck to get to that INR to 3.0,” he said.
That said, targeting INR is also key to preventing the second clot after a patient has had a thrombotic event, according to Furie. “The more aggressive the anticoagulation, the lower the second thrombotic event rate,” he said.
Furie noted that while warfarin can be effective to this end, compliance can be problematic for some patients.
The advent of direct oral anti-coagulant (DOAC) drugs such as rivaroxaban (Xarelto, Janssen) dabigatran (Pradaxa, Boehringer Ingelheim) and apixaban (Eliquis, Bristol Myers Squibb) briefly gave the APS community hope. However, a growing body of data has led Furie to one key conclusion.
“It was exciting to think that maybe we could get rid of warfarin, but evidence is growing that DOACs are maybe not so good for this syndrome,” he said, and described the clinical conundrum faced by many rheumatologists and their APS patients. “Is it better to be on a DOAC than to be a non-compliant warfarin patient?”
Looking into the pipeline, Furie reviewed some B- and plasma-cell targeted therapies. Rituximab (Rituxan, Genentech) has shown some capacity in normalization of aPL antibodies, as has belimumab (Benlysta, GlaxoSmithKline). Plasma cell targets such as proteasome inhibition and antibodies to CD38 also are under investigation, along with the Fc receptor protein, which may accelerate IgG clearance.
Hydroxychloroquine may have some efficacy in APS, as well, but Furie stressed that it is “unclear” exactly how. “Targeting the complement system may have benefit, but this is just theoretical,” he added.
In the end, Furie believes that each clinician treating APS is more or less left to assess each patient individually and rely on their own experience with the various drugs. “Everybody has their pet theory,” he said.
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Furie R. Antiphospholipid Syndrome: It’s More Thank You Think. Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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