Study designs for lupus

The most comprehensive clinical trial program in lupus to date

Explore the studies:

Study design for adult lupus trials

Be-SLE study parameters

BLISS-76 LTE study design

EMBRACE trial parameters

OBSErve US study design

Early use in lupus study design

Organ damage PSM study design

Long-term extension study design

PLUTO trial study design

Early use in lupus pooled data study design

SRI-4 at Week 52

  • ≥4-point reduction in the SELENA-SLEDAI score, and
  • No new BILAG A organ domain score or 2 new BILAG B organ domain scores, and
  • No worsening (<0.30-point increase) in PGA score

Study design for adult lupus trials

Phase III trials in adults were randomized, double-blind, and placebo-controlled, and assessed IV and SC methods of administration.

BLISS-SC (52-week duration)1
Treatment arms Regions
  • BENLYSTA SC 200 mg + ST (n=556)
  • Placebo + ST (n=280)
 177 centers throughout North America, South America, Europe, and Asia
BLISS-52 (52-week duration)2
Treatment arms Regions
  • BENLYSTA IV 1 mg/kg* + ST (n=288)
  • BENLYSTA IV 10 mg/kg + ST (n=290)
  • Placebo + ST (n=287)
 92 centers throughout South America, Asia, Eastern Europe, and Australia
BLISS-76 (76-week duration, primary endpoint measured at Week 52)3
Treatment arms Regions
  • BENLYSTA IV 1 mg/kg* + ST (n=271)
  • BENLYSTA IV 10 mg/kg + ST (n=273)
  • Placebo + ST (n=275)
 136 centers throughout North America and Europe
EMBRACE (52-week duration)4
Treatment arms Regions
  • BENLYSTA IV 10 mg/kg + ST (n=299)
  • Placebo + ST (n=149)
 88 centers throughout North America, South America, South Africa, and Europe
NE Asia (52-week duration)5
Treatment arms Regions
  • BENLYSTA IV 10 mg/kg + ST (n=451)
  • Placebo + ST (n=226)
 49 centers throughout China, Japan, and South Korea

Key inclusion criteria1-4,6,7

  • Patients were ≥18 years of age
  • Patients were self-identified as Black race (EMBRACE)
  • Patients were diagnosed with SLE according to the ACR criteria
  • Patients met ≥1 of the following:
    • ANA titer ≥1:80
    • Anti-dsDNA autoantibodies ≥30 IU/mL
  • Patients were receiving stable doses of any of the following, alone or in combination, for ≥30 days:
    • Antimalarial
    • Immunosuppressant
    • Corticosteroid
    • NSAID
  • Patients had active disease†
    • SELENA-SLEDAI score ≥8 (BLISS-SC, EMBRACE, NEA)
    • SELENA-SLEDAI score ≥6 (BLISS-52 and BLISS-76)

Key exclusion criteria1-4,6,7

  • Severe active lupus nephritis
    • Proteinuria >6 g over 24 hours or equivalent with spot urine protein:creatinine ratio
    • Serum creatinine >2.5 mg/dL
    • Required hemodialysis within 90 days of study entry
    • Required high-dose prednisone (>100 mg/day) within 90 days of study entry
  • Severe active CNS lupus
    • Patient required therapeutic intervention for any of the following within 60 days of study entry:
      • Seizures, psychosis, organic brain syndrome, CVA, cerebritis, or CNS vasculitis
  • Use of other biologics or IV cyclophosphamide was not permitted
  • *The 1-mg/kg dose is not recommended.
  • †Can include clinical (eg, arthritis, rash, and hair loss) and serological (eg, decreased complement and anti-dsDNA) SLE manifestations.
  • ACR = American College of Rheumatology; ANA = antinuclear antibody; anti-dsDNA = anti-double–stranded DNA; BILAG = British Isles Lupus Assessment Group; CNS = central nervous system; CVA = cerebrovascular accident; IV = intravenous; NEA = Northeast Asia; NSAID = nonsteroidal anti-inflammatory drug; PGA = Physician’s Global Assessment; SC = subcutaneous; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SLE = systemic lupus erythematosus; SRI = SLE Responder Index; ST = standard therapy.

Pivotal study endpoints1-3

Endpoints were analyzed in a hierarchical manner—if at any point statistical significance was not met, subsequent endpoints could not be considered significant.

    View efficacy for lupus

    Be-SLE study parameters6,10

    Post hoc pooled analysis of 5 double-blind placebo-controlled studies evaluating BENLYSTA

    Comparison for all efficacy endpoints:

    • Pooled BENLYSTA (10 mg/kg IV + 200 mg SC) vs pooled placebo (IV + SC)

    Analysis parameters

    Studies

    • BLISS-52
    • BLISS-76
    • NE Asia
    • EMBRACE*
    • BLISS-SC

    Patients evaluated

    • BENLYSTA + ST (n=1869)
    • Placebo + ST (n=1217)

    Endpoints

    SRI-4 subgroups

    • Severe flares and subgroups
    • Organ domains
    • Steroid outcomes
    • FACIT-Fatigue

    Key limitations:

    • Post hoc analysis
    • Pooled dosage groups
    • Results not adjusted for multiple comparisons
    • Individual endpoints may not have been achieved in all clinical studies pooled for this analysis

    * The primary endpoint (SRI-4 at Week 52) was not met in EMBRACE.

    View efficacy for lupus

    BLISS-76 LTE study design11

    US patients who completed the BLISS-76 Phase III trial were eligible for the BLISS-76 LTE open-label trial

    Trial parameters

    Study details

    • Multicenter US extension study (up to 8 years)
      • BENLYSTA IV 10 mg/kg + ST*

    Patients enrolled

    • N=268 (US sites only)

    Endpoints

    Assessed every 48 weeks

    • Primary: safety
      • AEs, AESI, vital signs, laboratory measures, SDI
    • Other
      • Efficacy by SRI-4
      • Disease activity scores
      • Flare rates
      • Steroid use

    Key limitations:

    • Open-label design with lack of comparator arm
    • Selection bias and responder bias may be present
    • Pooled dosage groups
    • Small group of patients at later time points

    * Patients who received placebo in BLISS-76 received 10 mg/kg BENLYSTA in the LTE study, and patients who received BENLYSTA continued to receive the same dose (1 or 10 mg/kg IV every 28 days) plus standard therapy. Following a protocol amendment in March 2011, patients receiving 1 mg/kg BENLYSTA had their dose increased to 10 mg/kg.

    AE = adverse event; AESI = adverse events of special interest; LTE = long-term extension; SC = subcutaneous; SDI = SLICC/ACR Damage Index; SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology.

    View efficacy for lupus

    EMBRACE trial parameters4

    Studies

    • Randomized
    • Double-blind
    • Placebo-controlled
    • 52-week duration

    Patients evaluated

    • BENLYSTA IV 10 mg/kg + ST (n=299)
    • Placebo + ST (n=149)

    Regions

    • 88 centers throughout North America, South America, South Africa, and Europe
    • mITT population: all patients who were randomized and received at least one dose of study treatment (48 patients from 3 sites were excluded due to non-compliance).
    • mITT = modified intention-to-treat.

    EMBRACE study endpoints4,7

    Endpoints were analyzed in a hierarchical manner—if at any point statistical significance was not met, subsequent endpoints could not be considered significant.

     

    Primary endpoint

    SRI-SLEDAI–2K at Week 52

    • ≥4-point reduction in the modified SELENA-SLEDAI score using SLEDAI-2K scoring for proteinuria, and
    • No new British Isles Lupus Assessment Group (BILAG) A or 2 new BILAG B organ domain scores, and
    • No worsening (≥0.30-point increase) in PGA score

     

    Secondary endpoint

    Severe flare

    • Time to first severe SLE flare as measured by the SFI

    Steroid reduction

    • Percentage of patients with a ≥25% mean prednisone dose decrease from baseline to ≤7.5 mg/day from weeks 40–52

    SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SFI = SELENA-SLEDAI Flare Index.

    View efficacy for lupus

    OBSErve US study design12,13

    An observational cohort study assessed the effectiveness of BENLYSTA 10 mg/kg + ST in adult patients with SLE over a 24-month period in US clinical practices across 27 states and included 92 rheumatologists (N=501). To qualify for enrollment, patients were required to have at least 8 infusions of BENLYSTA. The baseline was the date of first infusion. Physician-assessed clinical response was reviewed at 6-month intervals using medical charts and data collected using case report forms.

     

    Primary objective: Physician-assessed clinical response to BENLYSTA at 6 months. Between baseline and Month 6, ≥50% improvement in overall clinical response was reported for 48.7% of participants.

     

    Selected other objective: Changes in steroid use at 6-month intervals over a 24-month period.

     

    Study discontinuation: During the 2-year observation, 45% (n=224) were lost to follow-up or discontinued use of BENLYSTA. Common reasons for discontinuing BENLYSTA (n=122; 22.5%) include: patient request (40.2%), medication not effective (29.5%), and adverse event (12.5%).

     

    Key data limitations:

    • Lack of control group
    • Risk of selection bias
    • Validated disease assessment tool not consistently used
    • Patient attrition
    • Potential measurement error based on non-uniform categorization or interpretation of disease severity and treatment response
    • Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening

    Post hoc analysis in African-American and Hispanic patients

    The primary outcome measure was overall clinical response to BENLYSTA at the end of a 24-month period, based on physician’s assessment over the last 6-month period.

     

    Other clinical outcomes (assessed versus index at Month 6, 12, 18, and 24 post-index) included:

    • Physician-assessed SLE disease severity
    • Oral corticosteroid use
    • Utilization of assessment tools
    • Reasons for, and rate of, belimumab discontinuation

     

    Study discontinuation:

    • In the OBSErve US study, 501 patients with SLE were enrolled; 123 (24.6%) were African American and 88 (17.6%) were Hispanic, of whom 69 (56.1%) and 43 (48.9%), respectively, continued to receive BENLYSTA at Month 24
    • Of those patients who did not continue belimumab use over the 24 months, 26 (21.1%) African-American and 23 (26.1%) Hispanic patients were lost to follow-up, and 28 (22.8%) and 22 (25.0%), respectively, discontinued belimumab
    • The most common reasons for discontinuation in the African-American group were patient request (n=13) and medication inefficacy (n=7), and 2 patients discontinued belimumab due to an adverse event, while in the Hispanic group, the most common reasons for discontinuation were loss to follow-up (n=8) and loss of insurance or reimbursement (n=7)

     

    Care should be taken when interpreting the present findings due to the following limitations:

    • Patient attrition
    • Small sample size
    • Lack of a control group
    • Varied experience of participating clinicians with the clinical SLE tools
    • Analysis-by-responder bias
    • Use of subjective, non-validated assessments
    • Assessment tools not consistently used in approximately half of cases

    View efficacy for lupus

    Early use in lupus study design14

    Immunosuppressant use analysis

    Real-world evidence: immunosuppressant use analysis over a baseline period of 24 months and an observation period of up to 5 years post index
    • Retrospective, real-world, longitudinal cohort study based on administrative claims
    • Data from the Komodo Health Database of de-identified claims between January 2015 and December 2022 were used
    • A total of 6841 eligible adults with a diagnosis of lupus were identified at index on January 1, 2017
    • Patient follow-up was over a maximum of 60 months post-index
    • Patients were stratified into 2 cohorts: those initiating BENLYSTA with no immunosuppressant or after immunosuppressant use. Patients were then further stratified by their baseline SLE disease severity, defined using a previously published algorithm based on measures of SLE disease activity and expert clinical opinion. This analysis excluded patients with mild disease activity and those with history of use of >2 immunosuppressants during the baseline period
    • Immunosuppressants of interest were: azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, tacrolimus, and voclosporin
    • Results were reported descriptively and the time to OCS discontinuation was assessed using Kaplan-Meier

    Endpoints

    • Rate and severity of SLE flares
    • Time to organ damage occurrence
    • OCS use
    • All-cause HCRU

    Inclusion criteria

    • A lupus diagnosis before or on the index date based on:
      • ≥2 outpatient medical claims, OR
      • ≥1 inpatient/emergency department claim
    • Filled ≥1 prescription for BENLYSTA from January 2017 to May 2022
    • ≥18 years of age on the index date
    • ≥24 months of continuous enrollment before index date

    Exclusion criteria

    • Diagnosis of drug-induced lupus before the index date based on ≥1 outpatient, inpatient, or emergency department claim
    • Prescription of BENLYSTA or a Janus kinase inhibitor (ie, baricitinib, tofacitinib, upadacitinib, ruxolitinib, and fedratinib) during the baseline period (other biologic treatments were permitted)
    • Patients who had received ≥2 prior immunosuppressants during the baseline period

    Key data limitations

    • All results presented here are based on descriptive analyses and numerical differences are presented without statistical hypothesis testing
    • The 24-month baseline period may have resulted in small sample sizes
    • Medication usage:
      • The presence of a dispensed medication does not guarantee that the medication was taken as prescribed
      • Adherence to medication(s) was not measured
    • Difference between baseline clinical characteristics between cohorts
    • Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening
    • HCRU = healthcare resource utilization; OCS = oral corticosteroid.

    View efficacy for lupus

    Organ damage PSM study design15

    A post hoc, PSM comparative analysis was performed to assess the difference in organ damage (SDI) progression between patients in BLISS-76 LTE* and from the TLC.†

    PSM comparative analysis performed to assess the difference in organ damage (SDI) progression between patients in BLISS-76 LTE and from the TLC

    Endpoints15

    The primary objective was to compare organ damage progression (mean change in SDI score) from baseline to Year 5 in patients treated with BENLYSTA + ST or ST alone using propensity score matched data from the BLISS-76 LTE trial and the TLC. Secondary objectives included comparing the time to organ damage progression and the magnitude of damage accrual.

     

    Key limitations of this PSM study15

    • Post hoc analysis
    • Patients matched based on known variables only
    • Patients could not be matched by year of entry into the study
    • Differences in patient populations

     

    Patient characteristics

    Patients are matched based on propensity scores calculated using 17 predictors of organ damage, including:

    • Demographics (age, age squared, gender, race/ethnicity – Black or Asian/other, current smoker)
    • Clinical characteristics (history of: hypertension, dyslipidemia, proteinuria)
    • SLE-specific characteristics (SLE duration, number of ACR criteria at diagnosis, baseline SLEDAI score, baseline SDI – >1 or ≥2)
    • Medications (steroids, immunosuppressant(s), antimalarials)

    * To be eligible, patients on BENLYSTA had to be in the United States; regimen was BENLYSTA IV 10 mg/kg + ST.

    † Chosen based on its size, the extent of organ damage in patients, and the severity of disease activity. Regimen was ST alone.

    IV = intravenous; PSM = propensity score matching; TLC = Toronto Lupus Cohort.

    Organ damage home

    Long-term extension study design16

    This was a post hoc analysis of pooled data from 3 open-label LTE studies (LBSL02 Phase 2 LTE, BLISS-76 LTE, and BLISS-52 + BLISS-76 LTE, excluding US patients from BLISS-76).

     

    Patients received BENLYSTA IV 10 mg/kg + ST every 28 days and must have completed treatment through Week 72 of LBSL02 and BLISS-76, or Week 48 of BLISS-52.

     

    Endpoints

    The SDI score was assessed among eligible patients in the BLISS-76 and BLISS-52 + BLISS-76 LTE studies, within the high disease activity population (anti-dsDNA positive and low C3/C4), and the 5-year completer population (patients with ≥5 years of follow-up after their first dose of BENLYSTA).

     

    Patients in the originator studies who received BENLYSTA 1 mg/kg were transitioned to BENLYSTA 10 mg/kg upon entering the LTE. BENLYSTA 1 mg/kg is not an approved dose and not included in the data shown.

    Key data limitations

    • As the studies were open-label and did not have a control arm, causal inferences about the effect of BENLYSTA cannot be made
    • There was an increased number of withdrawals in later years, resulting in a small study population as compared to baseline
    • The Phase 2 study included some patients who were autoantibody negative at baseline. In the Phase 3 trials, all patients were autoantibody-positive
    • The baseline SDI scores varied among patients and are not reflected in this figure

    anti-dsDNA = anti-double–stranded DNA.

    Organ damage home

    PLUTO trial study design17

    PLUTO is the first 52-week Phase II, double-blind, placebo-controlled trial in children and adolescents with active lupus, evaluating the efficacy, safety, and pharmacokinetics of BENLYSTA.

    Treatment arms

    • BENLYSTA IV 10 mg/kg + ST (n=53)
    • Placebo + ST (n=40)

    Primary endpoint

    • Disease activity reduction as measured by SRI-4 at Week 52

    Key inclusion criteria6,17

    • Patients were aged 5-17 years
    • Patients were diagnosed with SLE according to the ACR criteria
    • Patients had active disease*
      • SELENA-SLEDAI score ≥6
    • Patients met ≥1 of the following:
      • ANA titer ≥1:80
      • Anti-dsDNA autoantibodies ≥30 IU/mL
    • Patients were receiving stable doses of any of the following, alone or in combination, for ≥30 days:
      • Antimalarial
      • Immunosuppressant
      • NSAID
      • Corticosteroids

    Key exclusion criteria6,17

    • Severe active CNS lupus
      • Patients required therapeutic intervention for any of the following CNS lupus symptoms within 60 days of study entry: seizures, psychosis, organic brain syndrome, CVA, cerebritis, or CNS vasculitis
    • Severe lupus kidney disease
    • Previous treatment with belimumab at any time
    • Treatment with B-cell targeted therapy in the past year
    • Received high-dose prednisone or equivalent (>1.5 mg/kg/day) or IV cyclophosphamide or new immunosuppressive/immunomodulatory or antimalarial agent within the past 60 days
    • *Can include clinical (eg, arthritis, rash, hair loss) and serological (eg, decreased complement and anti-dsDNA) SLE manifestations.
    • ACR = American College of Rheumatology; ANA = antinuclear antibody; anti-dsDNA = anti-double–stranded DNA; CNS = central nervous system; CVA = cerebrovascular accident; IV = intravenous; NSAID = nonsteroidal anti-inflammatory drug; ST = standard therapy.

    View efficacy for pediatric lupus

    Early use: post hoc analysis of pooled data from 5 pivotal trials6

    Efficacy endpoints

    • Proportion of patients with SRI-4 response* at 52 weeks
    • Proportion of patients with any on-study SFI flare† by Week 52
    • *SRI-4 response was defined as a ≥4-point reduction in SELENA-SLEDAI score from baseline, no new BILAG A organ domain score or 2 new BILAG B scores compared with baseline, and no worsening (increase <0.3) in PGA score versus baseline.
    • †Mild/moderate or severe flare as defined by a modification of the SELENA Trial flare criteria which excluded severe flares triggered only by an increase of the SELENA-SLEDAI score to >12.
    • Results are descriptive.

    Trial parameters6,18

    Study parameters

    • Phase III
    • Randomized
    • Placebo-controlled
    • Double-blind
    • 52-week duration

    Treatment arms

    • BENLYSTA (IV/SC) + AM and GC; no IS at baseline
    • Placebo + AM and GC + IS at baseline

    Regions

    • Central and South America, Asia, Australia, Canada, Europe, Israel, Mexico, New Zealand, South Africa, and the United States

    Study design6,18

    Post hoc summary of pooled monthly Week 52 data of adults with active SLE from five Phase III studies

    Study design: post hoc summary of pooled monthly Week 52 data of adults with active SLE from five Phase III studies

    Safety outcomes also included Phase 2 data (LBSL02).

     

    Key limitations

    • Post hoc analysis with pooled dosage groups
    • The results of the primary endpoint in the EMBRACE study did not reach statistical significance
    • Possible differences between matched populations
    • The same patient may not have responded at each visit
    • Individual endpoints may not have been achieved in all pooled studies
    • Individual studies were not designed or powered to analyze these cohorts
    • Results not adjusted for multiple comparisons

     

    Inclusion criteria6

    • ≥18 years of age
    • Patients had active SLE:
      • SELENA-SLEDAI score ≥6 (BLISS-52 and BLISS-76)
      • SELENA-SLEDAI score ≥8 (Northeast Asia, EMBRACE, and BLISS-SC)

    Baseline characteristics were broadly similar across treatment arms18

    Age (years), mean (SD) BENLYSTA N=552 IS N=358
      36 (11.5) 34 (10.9)
    Sex (female), n (%) BENLYSTA N=552 IS N=358
      524 (95) 334 (93)
    Race, n (%) BENLYSTA N=552 IS N=358
    Asian 194 (35) 144 (40)
    White 185 (34) 93 (26)
    Black African ancestry 108 (20) 82 (23)
    Native Alaskan/American Indian 65 (12) 39 (11)
    Multiracial 4 (1) 5 (1)
    SLE disease duration (years)*, median (IQR) BENLYSTA N=552 IS N=358
      3.9 (1.2-7.4)† 4.2 (1.6-8.8)
    BILAG organ domain involvement, n (%) BENLYSTA N=552 IS N=358
    At least 1A or 2B 194 (35) 144 (40)
    At least 1A 185 (34) 93 (26)
    At least 1B 108 (20) 82 (23)
    No A or B 65 (12) 39 (11)
    SELENA-SLEDAI score, mean (SD) BENLYSTA N=552 IS N=358
      10 (3.4) 10 (3.7)
    ≤9, n (%) 234 (42) 154 (43)
    ≥10, n (%) 318 (58) 204 (57)
    PGA, n; mean (SD) BENLYSTA N=552 IS N=358
      550; 1.5 (0.45) 357; 1.5 (0.50)
    SDI, mean (SD) BENLYSTA N=552 IS N=358
      0.3 (0.73) 0.5 (1.03)
    • *Duration defined as: (screening date/treatment start date − SLE diagnosis date + 1)/365.25.
    • †No data for one patient.
    • AM = antimalarial; GC = glucocorticoid; IQR = interquartile range; IS = immunosuppressants; SD = standard deviation; SDI = The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.

    View efficacy for lupus

    Learn more

    Real-world evidence

    See the effect of BENLYSTA on organ damage progression.

    SEE THE EFFECT ON ORGAN DAMAGE

    Safety profile

    Well-established safety profile based on the largest clinical trial program in lupus and lupus nephritis.

    SEE SAFETY PROFILE

    Indication & Safety Info

    Indication

    Important Safety Information

    Indication

    BENLYSTA is indicated for patients aged ≥5 with active systemic lupus erythematosus (SLE) or active lupus nephritis who are receiving standard therapy. BENLYSTA is not recommended in patients with severe active central nervous system lupus.

    Important Safety Information

    CONTRAINDICATION

    Previous anaphylaxis with BENLYSTA.

    WARNINGS AND PRECAUTIONS

    Serious Infections: Serious and sometimes fatal infections have been reported and occurred more frequently with BENLYSTA. Use caution in patients with severe or chronic infections, and consider interrupting therapy in patients with a new infection.

     

    Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported. If PML is suspected, immunosuppressant therapy, including BENLYSTA, must be suspended until PML is excluded. If confirmed, stop immunosuppressant therapy, including BENLYSTA.

     

    Hypersensitivity Reactions (Including Anaphylaxis): Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported. Generally, reactions occurred within hours of the infusion but may occur later, including in patients who have previously tolerated BENLYSTA. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Monitor patients during and after treatment and be prepared to manage anaphylaxis and infusion-related reactions. Be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. Discontinue immediately in the event of a serious reaction. With intravenous administration, if an infusion reaction develops, slow or interrupt the infusion.

     

    Depression and Suicidality: Depression and suicidality were reported in patients receiving BENLYSTA. Before adding BENLYSTA, assess patients’ risk of depression and suicide and monitor them during treatment. Instruct patients/caregivers to contact their HCP if they experience new/worsening depression, suicidal thoughts/behavior, or other mood changes.

     

    Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of BENLYSTA on the development of malignancies is unknown.

     

    Immunization: Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established.

     

    Use With Biologic Therapies: 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. 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.

     

    ADVERSE REACTIONS

    The most common serious adverse reactions in adult SLE clinical trials were serious infections; some were fatal. The most common adverse reactions (≥5%) were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous injection).

     

    Adverse reactions reported in clinical trials with SLE pediatric patients (≥5 years) and adult patients with lupus nephritis were consistent with those observed in adult SLE trials.

     

    USE IN SPECIFIC POPULATIONS

    Pregnancy: There are insufficient data in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. After a risk/benefit assessment, if prevention is warranted, women of childbearing potential should use contraception during treatment and for ≥4 months after the final treatment.

     

    Pregnancy Registry: HCPs 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/.

     

    Please see full Prescribing Information and Medication Guide for BENLYSTA.

    To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
    FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    References

    1. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two–week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016-1027.

    2. Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-731.

    3. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918-3930.

    4. Ginzler E, Guedes Barbosa LS, D'Cruz D, et al. Phase III/IV, randomized, fifty-two–week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. 2022;74(1):112-123.

    5. Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018;77(3):355-363.

    6. Data on file, GSK.

    7. Ginzler E, Guedes Barbosa LS, D’Cruz D, et al. Phase III/IV, randomized, fifty-two–week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. 2022;74(1)(suppl):1-21.

    8. Petri M, Kim MY, Kalunian K, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24):2550-2558.

    9. Petri M, Kim MY, Kalunian K, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24)(suppl):1-3.

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