Source: FDA, National Drug Code (US) Revision Year: 2024
BENLYSTA is contraindicated in patients who have had anaphylaxis with belimumab.
Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Overall, the incidence of serious infections in controlled trials was similar in patients receiving BENLYSTA compared with placebo, whereas fatal infections occurred more frequently in patients receiving BENLYSTA [see Adverse Reactions (6.1)].
Consider the risk and benefit before initiating treatment with BENLYSTA in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA in patients who develop a new infection while receiving it and monitor these patients closely.
Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. Consider the diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms and consult with a neurologist or other appropriate specialist as clinically indicated. In patients with suspected PML, immunosuppressant therapy, including BENLYSTA, must be suspended until PML has been excluded. If PML is confirmed, immunosuppressant therapy, including BENLYSTA, must be discontinued.
Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported in association with BENLYSTA [see Adverse Reactions (6.1)]. These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema have been reported and typically occurred up to a week following the most recent infusion. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of BENLYSTA. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk.
Due to overlap in signs and symptoms, it was not possible to distinguish between hypersensitivity reactions and infusion-related reactions in all cases. In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, some patients (13%) received premedication, which may have mitigated or masked a hypersensitivity response or infusion-related reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of hypersensitivity reactions or infusion-related reaction.
BENLYSTA for intravenous use should be administered by healthcare providers prepared to manage anaphylaxis and infusion-related reactions. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. In the event of a serious reaction, discontinue BENLYSTA immediately and administer appropriate medical therapy. With intravenous administration, the infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Monitor patients during infusion and for an appropriate period of time after intravenous administration of BENLYSTA. Consider administering premedication as prophylaxis prior to intravenous dosing [see Dosage and Administration (2.2)].
Inform patients receiving BENLYSTA of the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical care should a reaction occur.
In controlled clinical trials, depression and suicidality were reported in patients receiving BENLYSTA [see Adverse Reactions (6.1)]. Assess the risk of depression and suicide considering the patient’s medical history and current psychiatric status before treatment with BENLYSTA and continue to monitor patients during treatment. Instruct patients receiving BENLYSTA (and caregivers, if applicable) to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts or behavior, or other mood changes. Consider the risk and benefit of continued treatment with BENLYSTA for patients who develop such symptoms.
There is an increased risk of malignancies with the use of immunosuppressants. The impact of treatment with BENLYSTA on the development of malignancies is not known [see Adverse Reactions (6.1)].
Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing BENLYSTA. In patients who develop malignancies, consider the risk and benefit of continued treatment with BENLYSTA.
Because of its mechanism of action, BENLYSTA may interfere with the response to immunizations. Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving BENLYSTA or the effect of BENLYSTA on new immunizations.
Available data do not support the safety and efficacy of concomitant use of BENLYSTA with rituximab in patients with SLE. An increased incidence of serious infections and post-injection systemic reactions in patients receiving BENLYSTA concomitantly with rituximab compared to patients receiving BENLYSTA alone has been observed [see Adverse Reactions (6.1)]. The safety and efficacy of BENLYSTA concomitantly with other biologic therapies, including B-cell-targeted therapies, have not been established. Caution should be exercised if BENLYSTA is administered in combination with other biologic therapies [see Warnings and Precautions (5)].
The following serious adverse reactions are described below and in the Warnings and Precautions section:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in Table 1 reflect exposure to BENLYSTA administered intravenously plus standard therapy compared with placebo plus standard therapy in 2,133 adult patients with SLE in 3 controlled trials (Trials 1, 2, and 3). Patients received BENLYSTA plus standard therapy at doses of 1 mg/kg (n=673), 4 mg/kg (n=111; Trial 1 only), or 10 mg/kg (n=674), or placebo plus standard therapy (n=675) intravenously over a 1‑hour period on Days 0, 14, 28, and then every 28 days. In 2 of the trials (Trial 1 and Trial 3), treatment was given for 48 weeks, while in the other trial (Trial 2) treatment was given for 72 weeks [see Clinical Studies (14.1)]. Because there was no apparent dose-related increase in the majority of adverse events observed with BENLYSTA, the safety data summarized below are presented for the 3 intravenous doses pooled, unless otherwise indicated; the adverse reaction table displays the results for the recommended intravenous dose of 10 mg/kg compared with placebo.
In these trials, 93% of patients treated with BENLYSTA plus standard therapy reported an adverse event compared with 92% treated with placebo plus standard therapy.
The most common serious adverse events were serious infections (6% and 5.2% in the groups receiving BENLYSTA and placebo plus standard therapy, respectively), some of which were fatal.
The most commonly reported adverse events, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.
The proportion of patients who discontinued treatment due to any adverse reaction during the controlled clinical trials was 6.2% for patients receiving BENLYSTA plus standard therapy and 7.1% for patients receiving placebo plus standard therapy. The most common adverse reactions resulting in discontinuation of treatment (≥1% of patients receiving BENLYSTA or placebo) were infusion reactions (1.6% BENLYSTA and 0.9% placebo), lupus nephritis (0.7% BENLYSTA and 1.2% placebo), and infections (0.7% BENLYSTA and 1% placebo).
Table 1 lists adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received BENLYSTA 10 mg/kg plus standard therapy and at an incidence at least 1% greater than that observed with placebo plus standard therapy in 3 controlled trials (Trials 1, 2, and 3).
Table 1. Incidence of Adverse Reactions Occurring in at Least 3% of Adult Patients with SLE Treated with BENLYSTA 10 mg/kg plus Standard Therapy and at Least 1% More Frequently than in Patients Receiving Placebo plus Standard Therapy:
| Adverse Reactions | BENLYSTA 10 mg/kg + Standard Therapy (n=674) % | Placebo + Standard Therapy (n=675) % |
|---|---|---|
| Nausea | 15 | 12 |
| Diarrhea | 12 | 9 |
| Pyrexia | 10 | 8 |
| Nasopharyngitis | 9 | 7 |
| Bronchitis | 9 | 5 |
| Insomnia | 7 | 5 |
| Pain in extremity | 6 | 4 |
| Depression | 5 | 4 |
| Migraine | 5 | 4 |
| Pharyngitis | 5 | 3 |
| Cystitis | 4 | 3 |
| Leukopenia | 4 | 2 |
| Gastroenteritis viral | 3 | 1 |
Infections: In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, the overall incidence of infections was 71% in patients receiving BENLYSTA compared with 67% in patients receiving placebo. The most frequent infections (>5% of patients receiving BENLYSTA) were upper respiratory tract infection, urinary tract infection, nasopharyngitis, sinusitis, bronchitis, and influenza. Infections leading to discontinuation of treatment occurred in 0.7% of patients receiving BENLYSTA and 1.0% of patients receiving placebo.
In a randomized, double-blind, placebo-controlled, 104-week trial of active lupus nephritis in adults receiving BENLYSTA administered intravenously (N=448), the overall incidence of infections was 82% in patients receiving BENLYSTA compared with 76% in patients receiving placebo.
Serious Infections: In controlled trials of BENLYSTA administered intravenously in adults with SLE, the incidence of serious infections was 6.0% in patients receiving BENLYSTA and 5.2% in patients receiving placebo. The most frequent serious infections included pneumonia, urinary tract infections, cellulitis, and bronchitis. Fatal infections occurred in 0.3% (4/1,458) of patients receiving BENLYSTA and in 0.1% (1/675) of patients receiving placebo.
In a randomized, double-blind, placebo-controlled, 104-week trial of active lupus nephritis in adults receiving BENLYSTA administered intravenously, serious infections occurred in 14% of patients receiving BENLYSTA and in 17% of patients receiving placebo. Fatal infections occurred in 0.9% (2/224) of patients receiving BENLYSTA and in 0.9% (2/224) of patients receiving placebo.
In a randomized, double-blind, placebo-controlled, 52-week, postmarketing safety trial of BENLYSTA administered intravenously in adults with SLE (N=4,003), the incidence of serious infections was 3.7% in patients receiving BENLYSTA compared with 4.1% in patients receiving placebo. Serious infections leading to discontinuation of treatment occurred in 1.0% of patients receiving BENLYSTA and in 0.9% of patients receiving placebo. Fatal infections occurred in 0.45% (9/2,002) of patients receiving BENLYSTA and in 0.15% (3/2,001) of patients receiving placebo, where the incidence of all-cause mortality was 0.50% (10/2,002) in patients receiving BENLYSTA and 0.40% (8/2,001) in patients receiving placebo.
Hypersensitivity Reactions, including Anaphylaxis: In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, hypersensitivity reactions (occurring on the same day of infusion) were reported in 13% (191/1,458) of patients receiving BENLYSTA and 11% (76/675) of patients receiving placebo. Anaphylaxis was observed in 0.6% (9/1,458) of patients receiving BENLYSTA and 0.4% (3/675) of patients receiving placebo. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.
Infusion-Related Reactions: In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, adverse events associated with the infusion (occurring on the same day of the infusion) were reported in 17% (251/1,458) of patients receiving BENLYSTA and 15% (99/675) of patients receiving placebo. Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% of patients receiving BENLYSTA and 0.4% of patients receiving placebo and included bradycardia, myalgia, headache, rash, urticaria, and hypotension. The most common infusion reactions (≥3% of patients receiving BENLYSTA) were headache, nausea, and skin reactions.
Depression and Suicidality: In controlled clinical trials of BENLYSTA administered intravenously in adults with SLE (N=2,133), psychiatric events were reported more frequently with BENLYSTA (16%) than with placebo (12%), primarily related to depression-related events (6.3% BENLYSTA; 4.7% placebo), insomnia (6% BENLYSTA; 5.3% placebo), and anxiety (3.9% BENLYSTA; 2.8% placebo). Serious psychiatric events were reported in 0.8% (12/1,458) of patients receiving BENLYSTA and 0.4% (3/675) of patients receiving placebo. Serious depression was reported in 0.4% (6/1,458) of patients receiving BENLYSTA and 0.1% (1/675) of patients receiving placebo. Two suicides (0.1%) were reported in patients receiving BENLYSTA (one with 10 mg/kg and one with 1 mg/kg).
In a randomized, double-blind, placebo-controlled, 52-week, postmarketing safety trial of BENLYSTA administered intravenously in adults with SLE (N=4,003), serious psychiatric events were reported in 1% (20/2,002) of patients receiving BENLYSTA and 0.3% (6/2,001) of patients receiving placebo. Serious depression was reported in 0.3% (7/2,002) of patients receiving BENLYSTA and in <0.1% (1/2,001) receiving placebo. The overall incidence of serious suicidal ideation or behavior or self-injury without suicidal intent was 0.7% (15/2,002) of patients receiving BENLYSTA and 0.2% (5/2,001) of patients receiving placebo. On the Columbia-Suicide Severity Rating Scale (C-SSRS), 2.4% (48/1,974) of patients receiving BENLYSTA reported suicidal ideation or behavior compared with 2% (39/1,988) of patients receiving placebo. No suicide was reported in either group.
The intravenous trials above did not exclude patients with a history of psychiatric disorders.
Malignancy: In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, malignancies (including non-melanoma skin cancers) were reported in 0.4% of patients receiving BENLYSTA and 0.4% of patients receiving placebo. In the intravenous controlled clinical trials, malignancies, excluding non-melanoma skin cancers, were observed in 0.2% (3/1,458) and 0.3% (2/675) of patients receiving BENLYSTA and placebo, respectively.
Black/African-American Patients: The safety of BENLYSTA 10 mg/kg administered intravenously plus standard therapy (n=331) compared with placebo plus standard therapy (n=165) in Black patients with SLE (Trial 4) was consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy in the overall population [see Clinical Studies (14.1)].
The safety of BENLYSTA 10 mg/kg administered intravenously plus standard therapy (n=224) compared with placebo plus standard therapy (n=224) was evaluated in adults with active lupus nephritis for up to 104 weeks (Trial 5) [see Clinical Studies (14.2)]. The adverse reactions observed were consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy in patients with SLE. Cases of myelosuppression, including febrile neutropenia, leukopenia, and pancytopenia, were observed in subjects who received induction therapy with cyclophosphamide followed by maintenance therapy with azathioprine, or mycophenolate.
The safety of BENLYSTA administered intravenously plus standard therapy (n=53) compared with placebo plus standard therapy (n=40) was evaluated in 93 pediatric patients with SLE (Trial 6). The adverse reactions observed were consistent with those observed in adults with SLE [see Clinical Studies (14.3)].
The data described below reflect exposure to BENLYSTA administered subcutaneously plus standard therapy compared with placebo plus standard therapy in 836 patients with SLE in a controlled trial (Trial 7). In addition to standard therapy, patients received BENLYSTA 200 mg (n=556) or placebo (n=280) (2:1 randomization) once weekly for up to 52 weeks [see Clinical Studies (14.4)].
In the trial, 81% of patients treated with BENLYSTA plus standard therapy reported an adverse event compared with 84% treated with placebo plus standard therapy. The proportion of patients who discontinued treatment due to any adverse reaction during the controlled clinical trial was 7.2% of patients receiving BENLYSTA plus standard therapy and 8.9% of patients receiving placebo plus standard therapy.
The safety profile observed for BENLYSTA administered subcutaneously plus standard therapy was consistent with the known safety profile of BENLYSTA administered intravenously plus standard therapy, with the exception of local injection site reactions.
Infections: In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N=836), the overall incidence of infections was 55% in patients receiving BENLYSTA compared with 57% in patients receiving placebo. The most commonly reported infections with BENLYSTA administered subcutaneously were similar to those reported with BENLYSTA administered intravenously.
Serious Infections: In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N=836), the incidence of serious infections was 4.1% in patients receiving BENLYSTA and 5.4% in patients receiving placebo. Fatal infections occurred in 0.5% (3/556) of patients receiving BENLYSTA and in none of the patients receiving placebo (0/280).
Depression and Suicidality: In a controlled trial of BENLYSTA administered subcutaneously in adults with SLE (N=836), which excluded patients with a history of psychiatric disorders, psychiatric events were reported in 6% of patients receiving BENLYSTA and 11% of patients receiving placebo. Depression-related events were reported in 2.7% (15/556) of patients receiving BENLYSTA and 3.6% (10/280) of patients receiving placebo. Serious psychiatric events were reported in 0.2% (1/556) of patients receiving BENLYSTA and in no patients receiving placebo. There were no serious depression-related events or suicides reported in either group. On the C‑SSRS, 1.3% (7/554) of patients receiving BENLYSTA reported suicidal ideation or behavior compared with 0.7% (2/277) of patients receiving placebo.
Malignancy: In a controlled clinical trial of BENLYSTA administered subcutaneously in adults with SLE (N=836), the reports of malignancies were similar to those reported with BENLYSTA administered intravenously.
Injection Site Reactions: In a controlled clinical trial of BENLYSTA administered subcutaneously in adults with SLE (N=836), the frequency of injection site reactions was 6.1% (34/556) for patients receiving BENLYSTA plus standard therapy and 2.5% (7/280) for patients receiving placebo plus standard therapy. These injection site reactions (most commonly pain, erythema, hematoma, pruritus, and induration) were mild to moderate in severity. The majority (94%) did not necessitate discontinuation of treatment.
BENLYSTA administered subcutaneously in combination with rituximab was studied in a Phase III, randomized, double-blind, placebo-controlled, 104-week study in adult patients with SLE. Patients were randomized to 1 of the 3 treatment arms: BENLYSTA with a single cycle of rituximab (n=144); BENLYSTA with placebo (n=72); BENLYSTA plus standard therapy (n=76). In general, adverse reactions were consistent with the known safety profile of BENLYSTA and rituximab. When compared with BENLYSTA and placebo or BENLYSTA plus standard therapy, BENLYSTA in combination with rituximab was associated with higher frequency of serious adverse events (13.9%, 19.7%, 22.2%), serious infections (2.8%, 5.3%, 9.0%), and post-injection systemic reactions (9.7%, 5.3%, 13.2%).
The following adverse reactions have been identified during postapproval use of BENLYSTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Formal drug interaction studies have not been performed with BENLYSTA. In clinical trials, BENLYSTA was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, cyclophosphamide, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG‑CoA reductase inhibitors (statins), and/or non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated [see Clinical Pharmacology (12.3)].
There is a pregnancy exposure registry that evaluates pregnancy outcomes in women with lupus exposed to BENLYSTA during pregnancy. Healthcare professionals are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/.
Available data on use of BENLYSTA in pregnant women, from observational studies, published case reports, and postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with SLE (see Clinical Considerations). Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant (see Clinical Considerations). In an animal combined embryo-fetal and pre- and post-natal development study with monkeys that received belimumab by intravenous administration, there was no evidence of fetal harm with exposures approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the exposure at the maximum recommended human dose (MRHD). Belimumab-related findings in monkey fetuses and/or infants included reductions of B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. The no-adverse-effect-level (NOAEL) was not identified for these findings; however, they were reversible within 3 to 12 months after the drug was discontinued (see Data). Based on animal data and the mechanism of action of belimumab, the immune system in infants of treated mothers may be adversely affected. It is unknown, based on available data, whether immune effects, if identified, are reversible [see Clinical Pharmacology (12.1)].
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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block.
Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to BENLYSTA in utero. Monitor an infant of a treated mother for B-cell reduction and other immune dysfunction [see Warnings and Precautions (5.5)].
In a combined embryo-fetal and pre- and post-natal development study, pregnant cynomolgus monkeys received belimumab at intravenous doses of 0, 5, or 150 mg/kg every 2 weeks from confirmation of pregnancy at Gestation Days (GD) 20 to 22, throughout the period of organogenesis (up to approximately GD 50), and continuing to either the day of scheduled cesarean section (GD 150 [late third trimester]) or the day of parturition. There was no evidence of maternal toxicity, effects on embryofetal and infant survival, or structural abnormalities at exposure approximately 9 times the MRHD of 10 mg/kg intravenously or 20 times the MRHD of 200 mg subcutaneously (on an AUC basis with maternal animal intravenous doses up to 150 mg/kg). Belimumab-related findings in mothers included reductions of immature and mature B-cell counts and in fetuses and/or infants included reductions of immature and mature B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, reduced spleen weights, increased IgG titers, and reduced IgM titers. B-cell counts in infant monkeys exposed to belimumab in utero recovered by 3 months of age and in mothers after 1 year. IgG and IgM levels in infant monkeys recovered by 6 months of age and the reductions in B-lymphocytes in the lymph nodes and spleen were reversed by 1 year of age. Belimumab crossed the placenta, as it was detected in fetal cord blood and amniotic fluid on GD 150.
No information is available on the presence of belimumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Belimumab was detected in the milk of cynomolgus monkeys; however, due to species-specific differences in lactation physiology, animal data may not predict drug levels in human milk. Maternal IgG is known to be present in human milk. If belimumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to belimumab are unknown. The lack of clinical data during lactation precludes clear determination of the risk of BENLYSTA to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BENLYSTA, and any potential adverse effects on the breastfed child from BENLYSTA or from the underlying maternal condition.
Following an assessment of benefit versus risk, if prevention of pregnancy is warranted, females of reproductive potential should use effective contraception during treatment and for at least 4 months after the final treatment.
Safety and effectiveness of BENLYSTA have been established for the treatment of SLE and lupus nephritis in pediatric patients 5 to 17 years old.
Use of BENLYSTA in pediatric patients with SLE is supported by evidence from pharmacokinetic (PK) and efficacy results from a pediatric study (Trial 6), as well as PK exposure and extrapolation of the established efficacy of BENYLSTA plus standard therapy from the Phase 3 intravenous studies in adults with SLE. A randomized, double‑blind, placebo‑controlled, PK, efficacy, and safety study (Trial 6) to evaluate intravenously administered BENLYSTA 10 mg/kg plus standard therapy compared with placebo plus standard therapy over 52 weeks was conducted in 93 pediatric patients with SLE. The proportion of pediatric patients achieving an SRI-4 response was higher in patients receiving BENLYSTA plus standard therapy compared with placebo plus standard therapy. Pediatric patients receiving BENLYSTA plus standard therapy also had a lower risk of experiencing a severe flare compared with placebo plus standard therapy [see Clinical Studies (14.3)]. Pharmacokinetics were evaluated in a total of 53 pediatric patients with SLE and were consistent with the adult population with SLE [see Clinical Pharmacology (12.3)].
Use of BENLYSTA in pediatric patients with active lupus nephritis is based on the extrapolation of efficacy from the intravenous study in adults (n=224) with active lupus nephritis, and supported by pharmacokinetic data from intravenous studies in adults (n=224) with active lupus nephritis and from pediatric patients (n=53) with SLE. Estimated belimumab exposures for pediatric patients were comparable to adults with active lupus nephritis [see Clinical Pharmacology (12.3)].
The safety and effectiveness of intravenous administration of BENLYSTA have not been established in pediatric patients younger than 5 years of age.
The safety and effectiveness of subcutaneous administration of BENLYSTA have not been established in pediatric patients younger than 18 years of age.
Clinical studies of BENLYSTA did not include sufficient numbers of subjects aged 65 or older to determine whether they respond differently from younger subjects. Use with caution in geriatric patients.
The safety and efficacy of BENLYSTA were evaluated in studies that included patients with SLE who had mild (creatinine clearance [CrCl] ≥60 and <90 mL/min), moderate (CrCl ≥30 and <60 mL/min), or severe (CrCl ≥15 and <30 mL/min) renal impairment. No dosage adjustment is recommended in patients with renal impairment.
No formal trials were conducted to examine the effects of hepatic impairment on the pharmacokinetics of belimumab. No dosage adjustment is recommended in patients with hepatic impairment.
In Trial 2 and Trial 3 (intravenous dosing), SLE Responder Index-4 (SRI-4) response rates were lower for Black patients receiving BENLYSTA plus standard therapy relative to Black patients receiving placebo plus standard therapy [see Clinical Studies (14.1)].
In Trial 4 (intravenous dosing), a 2:1 randomized, placebo-controlled trial in Black patients, SLE Responder Index (SRI-S2K) response rates were higher for Black patients receiving BENLYSTA plus standard therapy (49%) relative to Black patients receiving placebo plus standard therapy (42%). However, the treatment difference was not statistically significant [see Clinical Studies (14.1)].
In Trial 7 (subcutaneous dosing), SRI-4 response was 45% (26/58) in Black patients receiving BENLYSTA plus standard therapy compared with 39% (13/33) in Black patients receiving placebo plus standard therapy [see Clinical Studies (14.4)].
The safety profile of BENLYSTA in Black patients was consistent with the known safety profile of BENLYSTA administered in the overall population [see Adverse Reactions (6.1)].
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