Effectiveness of Belimumab Treatment in a Subpopulation of Systemic Lupus Erythematosus (SLE) Patients: a Pooled Analysis of BLISS-52 and BLISS-76
Effectiveness of Belimumab Treatment in a Subpopulation of Systemic Lupus Erythematosus (SLE) Patients: a Pooled Analysis of BLISS-52 and BLISS-76
This pooled analysis will assess data from the Phase 3 belimumab registration studies
 BLISS-52 (aka BEL110752) and BLISS-76 (aka BEL110751). The analysis was pre-planned and
 agreed prior to the unblinding of either study. The primary objective is to evaluate the
 impact of belimumab treatment on a more severe subpopulation of systemic lupus erythematosus
 (SLE) subjects from BLISS-52 and BLISS-76 to aid physicians and payers in decision making.
 Subjects are from the modified Intent-to-Treat (ITT) population defined as randomized
 subjects who received at least 1 dose of study agent. This more severe subpopulation will
 have renal, neurological, haematological, or cardiovascular/respiratory organ domain
 involvement (as defined by a British Isles Lupus Assessment Group (BILAG) domain score of A,
 B or C in at least one of the domains) at baseline AND anti-double-stranded deoxyribonucleic
 acid (anti-dsDNA) positive (≥ 30 IU/mL) at baseline OR low C3 and/or C4 complement relative
 to the normal range at baseline.
Inclusion Criteria

 -  Eligible subjects for BLISS-52 and BLISS-76 included:

 -  clinical diagnosis of systemic lupus erythematosus (SLE) according to the American
 College of Rheumatology (ACR) criteria

 -  "active" (systemic lupus erythematosus) SLE disease, defined as a safety of oestrogen
 in lupus national assessment (SELENA) systemic lupus erythematosus disease activity
 index (SLEDAI) disease activity score of at least 6 at screening

 -  an unequivocally positive antinuclear antibodies (ANA) test result, from 2 independent
 time points within the study screening period or 1 positive historical test result and
 1 positive test result during the screening period. ANA test results obtained in the
 screening period were only considered positive if the ANA titer ≥ 1:80 and/or
 anti-dsDNA serum antibody was ≥ 30 IU/mL

 -  on a stable SLE treatment regimen for at least 30 days prior to Day 0, which consisted
 of any of the following (alone or in combination): prednisone or equivalent (from 0 to
 40 mg/day when used in combination with other SLE treatment or from 7.5 to 40 mg/day
 alone), anti-malarials, non-steroidal anti inflammatory drugs (NSAIDs), or any
 immunosuppressive therapy (i.e., methotrexate, azathioprine, leflunomide, or
 mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide,
 6-mercaptopurine, or thalidomide).

 -  Additional inclusion criteria for the purpose of this analysis: subpopulation of
 patients from the pooled modified Intent-to-Treat population from BLISS-52 and
 BLISS-76 who have renal, neurological, haematological, or cardiovascular/respiratory
 organ domain involvement (as defined by a BILAG domain score of A, B or C in at least
 one of the domains) at baseline and 1 of the following:

 -  are anti-dsDNA positive (≥ 30 IU/mL) at baseline, OR

 -  have low C3 and/or C4 complement relative to the normal range at baseline.

 Exclusion Criteria:

 -  Key exclusion criteria for BLISS-52 and BLISS-76 included:

 -  severe active lupus nephritis or Central Nervous System (CNS) lupus

 -  pregnancy

 -  receipt of any B cell target therapy at any time

 -  receipt of an investigational agent within 60 days prior to Day 0 for non-biologics
 and within 1 year for biologics

 -  receipt of abatacept (within 1 year), intravenous (IV) cyclophosphamide (within 6
 months), anti-tumor necrosis factor (anti-TNF) therapy, anakinra, IV immunoglobulin
 (IVIG), prednisone > 100 mg/day, or plasmapheresis within 3 months, or live vaccine
 within 1 month.