Important Safety Information
for ORENCIA®
(abatacept)
Increased Risk of Infection with Concomitant Use
with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors:
Concurrent therapy with ORENCIA and a TNF antagonist is not
recommended. In controlled clinical trials, adult moderate to severe
rheumatoid arthritis (RA) patients receiving concomitant intravenous ORENCIA
and TNF antagonist therapy experienced more infections (63% vs 43%) and
serious infections (4.4% vs 0.8%) compared to patients treated with only TNF
antagonists, without an important enhancement of efficacy. Additionally,
concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK
inhibitors is not recommended.
Hypersensitivity Reactions: There were 2
cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with
adult RA patients treated with intravenous ORENCIA. Other reactions
potentially associated with drug hypersensitivity, such as hypotension,
urticaria, and dyspnea, each occurred in <0.9% of patients. There was one
case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials
(0.5%; n=190). In postmarketing experience, fatal anaphylaxis following the
first infusion of ORENCIA and life-threatening cases of angioedema have been
reported. Angioedema has occurred as early as after the first dose of
ORENCIA, but also has occurred with subsequent doses. Angioedema reactions
have occurred within hours of administration and in some instances had a
delayed onset (i.e., days). Appropriate medical support measures for
treating hypersensitivity reactions should be available for immediate use.
If an anaphylactic or other serious allergic reaction occurs, administration
of intravenous or subcutaneous ORENCIA should be stopped immediately and
permanently discontinued, with appropriate therapy instituted.
Infections: Serious infections, including
sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated
with intravenous ORENCIA and placebo, respectively. Some of these infections
have been fatal. Many of the serious infections have occurred in patients on
concomitant immunosuppressive therapy which, in addition to their underlying
disease, could further predispose them to infection. Caution should be
exercised in patients with a history of infection or underlying conditions
which may predispose them to infections. Treatment with ORENCIA should be
discontinued if a patient develops a serious infection. Patients should be
screened for tuberculosis and viral hepatitis in accordance with published
guidelines, and if positive, treated according to standard medical practice
prior to therapy with ORENCIA.
Immunizations: Prior to initiating ORENCIA
in pediatric and adult patients, update vaccinations in accordance with
current vaccination guidelines. ORENCIA-treated patients may receive current
non-live vaccines. Live vaccines should not be given concurrently with
ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the
effectiveness of some immunizations. In addition, it is unknown if the
immune response of an infant who was exposed in utero to abatacept and
subsequently administered a live vaccine is impacted. Risks and benefits
should be considered prior to vaccinating such infants.
Increased Risk of Adverse Reactions When Used in
Patients with Chronic Obstructive Pulmonary Disease (COPD): In
Study V, adult COPD patients treated with ORENCIA for RA developed adverse
reactions more frequently than those treated with placebo, including COPD
exacerbations, cough, rhonchi, and dyspnea. In the study, 97% of COPD
patients treated with ORENCIA developed adverse events versus 88% treated
with placebo. Respiratory disorders occurred more frequently in patients
treated with ORENCIA compared to those on placebo (43% vs 24%,
respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A
greater percentage of patients treated with ORENCIA developed a serious
adverse event compared to those on placebo (27% vs 6%), including COPD
exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)].
Use of ORENCIA in patients with COPD should be undertaken with caution, and
such patients monitored for worsening of their respiratory status.
Immunosuppression: In clinical trials in
adult RA patients, a higher rate of infections was seen in ORENCIA-treated
patients compared to placebo-treated patients. The impact of treatment with
ORENCIA on the development and course of malignancies is not fully
understood. There have been reports of malignancies, including skin cancer
in patients receiving ORENCIA. Periodic skin examinations are recommended
for all ORENCIA-treated patients, particularly those with risk factors for
skin cancer.
Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)
Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell
Transplant (HSCT): Post-Transplant Lymphoproliferative Disorder
(PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis
during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients
(3.4%) experienced PTLD. All the PTLD events were associated with
Epstein-Barr virus (EBV) infection. The range of time to onset of the event
was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in
accordance with institutional practices. Before administering ORENCIA,
provide recommended prophylaxis for EBV infection and continue for 6 months
post-transplantation to prevent EBV-associated PTLD. Cytomegalovirus (CMV)
invasive disease occurred in patients who received ORENCIA for aGVHD
prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7%
(n=8) experienced CMV invasive diseases up to day 225 post-transplant. The
median time to onset of the event was 91 days post-transplant. CMV invasive
diseases predominantly involved the gastrointestinal tract. Monitor patients
for CMV infection/reactivation for 6 months post-transplant regardless of
the results of donor and recipient pre-transplant CMV serology. Consider
prophylaxis for CMV infection/reactivation during treatment and for six
months following HSCT.
Blood Glucose Testing: ORENCIA for
intravenous administration contains maltose, which may result in falsely
elevated blood glucose readings on the day of infusion when using blood
glucose monitors with test strips utilizing glucose dehydrogenase
pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and
advising patients to use monitors that do not react with maltose, such as
those based on glucose dehydrogenase nicotine adenine dinucleotide
(GDH-NAD), glucose oxidase or glucose hexokinase test methods.
ORENCIA for subcutaneous (SC) administration does not contain maltose;
therefore, patients do not need to alter their glucose monitoring.
Pregnancy: There are no adequate and
well-controlled studies of ORENCIA use in pregnant women and the data with
ORENCIA use in pregnant women are insufficient to inform on drug-associated
risk.
Lactation: There is no information regarding
the presence of abatacept in human milk, the effects on the breastfed
infant, or the effects on milk production. However, abatacept was present in
the milk of lactating rats dosed with abatacept.
Most Serious Adverse Reactions: In
controlled clinical trials, adult RA patients experienced serious infections
(3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1%
placebo). In the GVHD-1 study, serious adverse reactions reported in >5% of
patients who received ORENCIA in combination with a calcineurin inhibitor
and methotrexate included pyrexia (20%), pneumonia (8%), acute kidney injury
(7%), diarrhea (6%), hypoxia (5%), and nausea (5%).
Malignancies: The overall frequency of
malignancies was similar between adult RA patients treated with ORENCIA or
placebo. However, more cases of lung cancer were observed in patients
treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of
lymphoma was seen compared to the general population; however, patients with
RA, particularly those with highly active disease, are at a higher risk for
the development of lymphoma. The potential role of ORENCIA in the
development of malignancies in humans is unknown.
Most Frequent Adverse Events (≥10%):
Headache, upper respiratory tract infection, nasopharyngitis, and nausea
were the most commonly reported adverse events in the adult RA clinical
studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough,
pyrexia, and abdominal pain. In general, the adverse events in pediatric
pJIA and adult PsA patients were similar in frequency and type to those seen
in adult RA patients. The most frequent adverse reactions of all grades
reported in ≥10% of patients with aGVHD who received ORENCIA with a
difference of ≥2% for the 7/8 cohort, 8/8 cohort ORENCIA arm, and 8/8 cohort
placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes
decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia
(28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%, and 22%),
pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney
injury (9%, 15%, and 10%), and hypermagnesemia (5%, 18%, 10%).
Incidence rates of grade 3 or 4 adverse reactions were
the same as incidence
rates of all grades, with the exception of grade 3 or 4 pyrexia in all arms
(9% [7/8 cohort], 10% [8/8 cohort, ORENCIA arm], and 4% [8/8 cohort, placebo
arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury
in the 7/8 cohort ORENCIA arm (7%). Clinically relevant adverse reactions in
<10% of patients who received ORENCIA in combination with calcineurin
inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.
Note concerning ORENCIA administration
options: ORENCIA may be administered as an intravenous infusion
only for patients 6 years of age and older. PJIA or pediatric PsA patients
may self-inject with ORENCIA or the patient’s caregiver may administer
ORENCIA if both the healthcare practitioner and the parent/legal guardian
determines it is appropriate. The ability of pediatric patients to
self-inject with the autoinjector has not been tested. ORENCIA for the
prophylaxis of aGVHD in patients undergoing HSCT may only be administered as
an intravenous (IV) infusion. The safety and effectiveness of ORENCIA have
not been established in pediatric patients younger than 2 years of age for
prophylaxis of aGVHD.
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