Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).

Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included.

EMBRACE: One Small Story in Lupus-One Giant Challenge in Clinical Trials.

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results.

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.

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race.

Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.

Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol.

Introduction: Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together.

Clinical response beyond the Systemic Lupus Erythematosus Responder Index: post-hoc analysis of the BLISS-SC study.

Objective: The Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE.

Methods: This was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC).

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study.

Objective: To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).

Methods: Patients with moderate-to-severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52.

Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus .

Objective: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).

Methods: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic.

Pharmacokinetics and Tolerability of Single-Ascending Doses of Desvenlafaxine Administered to Children and Adolescents with Major Depressive Disorder.

Objective: To investigate the safety and pharmacokinetic profile of ascending doses of desvenlafaxine in children and adolescents with major depressive disorder. Assessment of the effect of desvenlafaxine on depression symptoms was exploratory.

Methods: The 8-week, open-label study included an initial 3.

Relative Bioavailability of a Single Dose of Belimumab Administered Subcutaneously by Prefilled Syringe or Autoinjector in Healthy Subjects.

Intravenous belimumab is approved for the treatment of systemic lupus erythematosus; subcutaneous self-administration would enable greater patient access. This study assessed relative bioavailability, tolerability, and safety of 1 subcutaneous dose of self-administered belimumab by healthy subjects using a single-use autoinjector or prefilled syringe. Subjects (randomized 1:1:1:1) self-administered belimumab 200 mg subcutaneously (abdomen or thigh) by prefilled syringe or autoinjector.

Safety and tolerability of desvenlafaxine in children and adolescents with major depressive disorder.

Objective: The purpose of this study was to assess long-term safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in children and adolescents with major depressive disorder (MDD).

Methods: An 8 week, multicenter, open-label, fixed-dose study of children (ages 7-11 years) and adolescents (ages 12-17 years) with MDD was followed by a 6 month, flexible-dose extension study. Patients were administered desvenlafaxine 10-100 mg/day (children) or 25-200 mg/day (adolescents) for a total of 8 months.

Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies.

Background: Major depressive disorder (MDD) is a common, chronic illness associated with substantial disability and economic burden. Although a number of effective antidepressants are available, the need for new medications that are effective and well tolerated remains.

Objective: The aim of this study was to compare the efficacy and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/d with placebo for MDD.