CLINICAL NEWS
Thirty-four patients (37%) achieved sustained
ADAMTS13 activity recovery during a median follow-up
of 31.5 months (range = 18-65 months) after pre-emptive
rituximab. “These patients required no further courses
of rituximab and were therefore considered as long-term
responders,” the authors reported.
Thirteen patients (14%) had undetectable ADAMTS13
activity after the first course of rituximab, and 19 pa-
tients (20.7%) experienced mild adverse effects (includ-
ing pruritus, rhinitis, dyspnea, nausea and vomiting,
hypotension, and arrhythmia). Ten received repeated
rituximab administration; of these, four experienced
persistent ADAMTS13 deficiency and six had recovery
of ADAMTS13 activity.
Levels were eventually normalized with cyclosporine
A in two of the three patients with severe ADAMTS13
activity after the first course of rituximab but remained
undetectable in the remaining patient.
“In these patients, further studies [are needed] to de-
fine the best approach, particularly in regard to whether
clinicians should intensify immunosuppression or use a
tight watch-and-wait approach,” Dr. Coppo explained. “In
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on COPIKTRA
CYP3A Inducers: Co-administration with a strong CYP3A inducer decreases duvelisib
area under the curve (AUC) [see Clinical Pharmacology (12.3)], which may reduce
COPIKTRA efficacy. Avoid co-administration of COPIKTRA with strong CYP3A4
inducers. CYP3A Inhibitors: Co-administration with a strong CYP3A inhibitor
increases duvelisib AUC [see Clinical Pharmacology (12.3)], which may increase
the risk of COPIKTRA toxicities. Reduce COPIKTRA dose to 15 mg BID when
co-administered with a strong CYP3A4 inhibitor [see Dosage and Administration (2.4)].
7.2 Effects of COPIKTRA on Other Drugs
CYP3A Substrates: Co-administration with COPIKTRA increases AUC of a sensitive
CYP3A4 substrate [see Clinical Pharmacology (12.3)] which may increase the risk of
toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4
substrate and monitor for signs of toxicities of the co-administered sensitive CYP3A
substrate.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary: Based on findings from animal studies and the mechanism of action,
COPIKTRA can cause fetal harm when administered to a pregnant woman [see
Clinical Pharmacology (12.1)]. There are no available data in pregnant women to
inform the drug-associated risk. The estimated background risk of major birth
defects and miscarriage for the indicated population is unknown. All pregnancies
have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
8.2 Lactation
Risk Summary: There are no data on the presence of duvelisib and/or its metabolites
in human milk, the effects on the breastfed child, or on milk production. Because of
the potential for serious adverse reactions from duvelisib in a breastfed child, advise
lactating women not to breastfeed while taking COPIKTRA and for at least 1 month
after the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing: COPIKTRA can cause fetal harm when administered to a pregnant
woman [see Use in Specific Populations (8.1)]. Conduct pregnancy testing before
initiation of COPIKTRA treatment.
Contraception
Females Based on animal studies, COPIKTRA can cause fetal harm when
administered to a pregnant woman. Advise females of reproductive potential to use
effective contraception during treatment with COPIKTRA and for at least 1 month
after the last dose.
Males Advise male patients with female partners of reproductive potential to use
effective contraception during treatment with COPIKTRA and for at least 1 month
after the last dose.
Infertility Based on testicular findings in animals, male fertility may be impaired by
treatment with COPIKTRA [see Nonclinical Toxicology (13.1)]. There are no data on
the effect of COPIKTRA on human fertility.
this specific small group of patients, the risk-benefit bal-
ance of a more intensive immunosuppressive treatment
needs additional evaluation.”
“An important message is that patients may need
additional infusions of rituximab during follow-up,
because anti-ADAMTS13 antibodies may reoccur
along with peripheral B-cell recovery, leading to further
decreases of ADAMTS13 activity,” Dr. Coppo said.
“Therefore, iTTP should now be considered a chronic
disease, and patients with a history of iTTP should be
offered long-term follow-up with regular ADAMTS13
activity assessment.”
The investigators compared study
participants’ ADAMTS13 activity with
that of 23 historical controls who had
persistent, severe ADAMTS13 defi-
ciency and no history of pre-emptive
rituximab. During a median follow-up
of seven years (range = 5-11 years),
their rate of clinical relapse was 74
percent, corresponding to a median
cumulative incidence of relapse of
0.26 episodes per year (range = 0.19-
0.46). Again, these data suggest that
pre-emptive rituximab reduced the
risk of relapse, compared with no pre-
emptive rituximab (p<0.001).
“Our hope is that this strategy
will become widespread among the
other groups involved in the manage-
ment of iTTP and that it will lead to a
substantial decrease of relapse of this
debilitating disease worldwide,” Dr.
Coppo said.
The researchers noted that partici-
pants were treated at different times
in the course of their disease, which
could potentially limit the study’s
findings. “This raises the possibility
that other changes in iTTP manage-
ment could have affected the results,”
they wrote. The small sample size also
may limit the generalizability of the
findings.
The authors report financial rela-
tionships with Alexion, Ablynx, Shire,
and Octapharma.
REFERENCE
Jestin M, Benhamou Y, Schelpe AS, et al. Preemptive rituximab
prevents long-term relapses in immune-mediated thrombotic
thrombocytopenic purpura. Blood. 2018 September 10. [Epub
ahead of print]
8.4 Pediatric Use
Safety and effectiveness of COPIKTRA have not been established in pediatric
patients. Pediatric studies have not been conducted.
8.5 Geriatric Use
Clinical trials of COPIKTRA included 270 (61%) patients that were 65 years of age
and older and 104 (24%) that were 75 years of age and older. No major differences
in efficacy or safety were observed between patients less than 65 years of age and
patients 65 years of age and older.
PM-US-DUV-18-0052
ASH Clinical News
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