mation, 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.
“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
A steering committee composed of
representatives from the European
Commission–funded RARE-Bestn -
Practices project and McMaster University in Hamilton, Canada, 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
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
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 microan-giopathy; 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 cer-
tainty of evidence, and most were
• Triple-therapy combination
treatment with corticosteroids,
heparin, and plasma exchange
or intravenous immunoglobulins
instead of a single agent or other
• Therapeutic dose anticoagulation
was one of only two treatment
recommendations to be consid-
ered “strong,” but use of direct
oral anticoagulants is not ad-
• Therapeutic plasma exchange
is recommended for use with
other therapies and should be
strongly considered for patients
with microangiopathic hemolytic
• 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 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
• 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
emphasised 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.
“Triple therapy was associated with a higher chance of
survival when compared to other combinations or to
none of these treatments.“