Is It Time for a Paradigm Shift for CAPS Treatment?

Newer treatment approaches that incorporate monoclonal antibodies reduce the mortality risk in patients with catastrophic antiphospholipid syndrome (CAPS), according to research presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress. The findings, according to lead author Philip A. Haddad, MD, MPH, from Louisiana State University Health Sciences Center, suggest that rituximab and eculizumab should be incorporated earlier into the treatment of the disease.

“CAPS is a fulminant variant of antiphospholipid syndrome characterized by multi-organ thrombosis and subsequent failure,” Dr. Haddad explained during his presentation. Traditional therapeutic options have consisted of a combination of anticoagulation, glucocorticoids, and plasma exchange with or without intravenous immunoglobulins, but CAPS mortality remains high. “Recently monoclonal antibodies rituximab and eculizumab have been used as salvage as well as primary therapy, with promising results,” he said.

In this study, Dr. Haddad and coauthors sought to assess the effects of different therapeutic approaches on clinical outcomes of patients with CAPS. They compiled a database that included 453 cases, then reviewed the mortality rates associated with the various treatment combinations.

As seen in the TABLE, mortality rates with the various treatment approaches ranged from 17% to 37%. Mortality was highest with the standard backbone combination of anticoagulation and glucocorticoids, but adding plasma exchange or intravenous immunoglobulin (IVIg) reduced the mortality rate. When IViG, rituximab, or eculizumab were added to the traditional backbone as salvage therapy, there was “a notable salvage power,” Dr. Haddad said.

“Since many cases that used rituximab and eculizumab did not follow the traditional therapeutic backbone combinations, we reanalyzed the data comparing the basic therapeutic backbones with the rituximab- and eculizumab-based combinations,” he added. “Mortality declined from 37% to 20% with plasma exchange, down to 16% with rituximab, and all the way to 6% with eculizumab combinations.”

Plasma exchange led to a reduction in mortality even in the absence of rituximab or eculizumab, the authors noted. However, this impact vanished when plasma exchange was combined with either monoclonal antibody.

The results of this analysis suggest that eculizumab may offer a greater mortality benefit than rituximab, Dr. Haddad said, noting that eculizumab successfully salvaged cases of rituximab failure 77% of the time.

Based on these findings, the researchers recommend a “paradigm shift” in CAPS treatment, consisting of frontline therapy with anticoagulation, glucocorticoids, and eculizumab with or without rituximab – along with appropriate therapies that target the underlying medical condition, such as antibiotics, chemoimmunotherapy, and immunosuppressants. Plasma exchange therapy could be used as adjunctive therapy in cases of more resistant disease, they added.

“Time is of the essence, and highly active agents should be used upfront in CAPS to significantly lower mortality and morbidity,” Dr. Haddad concluded.

The authors report no relevant conflicts of interest.


Haddad PA, Hammoud D, Gallagher K. The relative impact of treatment approaches on the outcome of catastrophic antiphospholipid syndrome (CAPS): analysis of an updated database. Abstract OC 07.5. Presented at ISTH 2020 Virtual Congress; July 12-14, 2020.