Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial)
نویسندگان
چکیده
OBJECTIVES Despite advances in systemic lupus erythematosus (SLE) treatment, many patients suffer from the disease and side effects. Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with SLE. METHODS In this double-blind, placebo-controlled study, patients with moderate-to-severe SLE were randomised to atacicept 75 mg or atacicept 150 mg administered subcutaneously, or placebo twice-weekly for 4 weeks, then weekly for 48 weeks. Primary and secondary efficacy measures were the proportion of patients experiencing at least one flare of British Isles Lupus Assessment Group A or B, and time to first flare, respectively. RESULTS Enrolment in the atacicept 150 mg arm was discontinued prematurely due to two deaths. In the intention-to-treat population (n=461), there was no difference in flare rates or time to first flare between atacicept 75 mg and placebo. Analysis of patients treated with atacicept 150 mg suggested beneficial effect versus placebo in flare rates (OR: 0.48, p=0.002) and time to first flare (HR: 0.56, p=0.009). Both atacicept doses were associated with reductions in total Ig levels and anti-dsDNA antibodies, and increases in C3 and C4 levels. Most treatment-emergent adverse events were mild or moderate. CONCLUSIONS There was no difference between atacicept 75 mg and placebo for flare rate or time to first flare. Analysis of atacicept 150 mg suggested benefit. TRIAL REGISTRATION NUMBER EudraCT: 2007-003698-13; NCT00624338.
منابع مشابه
The Efficacy of Mindfulness-Based Cognitive Therapy on General Health in Patients with Systemic Lupus Erythematosus: A Randomized Controlled Trial
Background & Aims: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, involving multiple organs and producing autoantibodies against different components of the cell. SLE is of unknown etiology with various clinical and laboratory manifestations. Different psychological disorders are seen in patients with SLE, including mood, anxiety, and cognitive disorders. This study w...
متن کاملBrain Single Photon Emission Computed Tomography Scan (SPECT) and Functional MRI in Systemic Lupus Erythematosus Patients with Cognitive Dysfunction: A Systematic Review
Objective(s): Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations. Cognitive dysfunction is one of the manifestations that could present prior to the emergence of any other neuropsychiatric involvements in SLE. Cognitive dysfunction is a subtle condition occurring with ahigh frequency. However, there is no data on the correlation of cognitive...
متن کاملEfficacy 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 prefil...
متن کاملAn Exploratory Dose-Escalating Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous Atacicept in Patients with Systemic Lupus Erythematosus
Atacicept, a recombinant fusion protein containing the extracellular, ligand-binding portion of the transmembrane activator and calcium modulator and cyclophilin-ligand interactor receptor, and the Fc portion of human immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte stimulator and a proliferation-inducing ligand, and may have utility as a treatment for B-cell-mediated di...
متن کاملAssessment of Association between Duffy Blood Group Phenotypes and Susceptibility to Systemic Lupus Erythematosus and its Severity
Background: Considering the role of Duffy antigenic system expression on RBCs as chemokines for inflammatory cytokines, expression of Duffy antigens as different phenotypes was studied in a group of patients with SLE. The association between different phenotypes of Duffy antigens and occurrence of SLE and its severity was assessed. Methods: This cross-sectional study was carried out on 100 pa...
متن کامل