MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.
Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).
CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.
At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.
CAPS Registry study
The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.
Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.
The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.
“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.
The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.
Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.
“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.
While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.
All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).
“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.
“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”
A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.
Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.
The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.
All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:
- Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
- Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
- Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
- Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
- Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
- Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
- Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.
The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.
None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.