Response to placebo in non-renal, non-neuropsychiatric systemic lupus erythematosus: a systematic review and pooled analysis

• Published in: Rheumatology (Oxford, England) England), 2021-01, Vol.60 (1), p.73-80
• Main Authors: Tselios, Konstantinos, Wakani, Laura, Gladman, Dafna D, Su, Jiandong, Urowitz, Murray B
• Format: Article
• Language: English
• Subjects: Antirheumatic Agents - therapeutic use; Biological Products - therapeutic use; Endpoint Determination; Humans; Lupus Erythematosus, Systemic - drug therapy; Placebo Effect; Randomized Controlled Trials as Topic
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keaa655

Abstract Objectives Most randomized controlled trials (RCTs) in SLE have failed to reach their respective end points, with the rates of response to placebo (plus standard-of-care treatment) being unexpectedly high. The aim of this systematic review was to quantify the response to placebo in non-renal, non-neuropsychiatric lupus. Methods The PubMed database was searched (from 2000 to December 2019) for phase II/III RCTs assessing the efficacy and safety of biologics in non-renal, non-neuropsychiatric SLE. Data on the efficacy and safety of the placebo-treated patients were collected in a pre-established data retrieval form. Descriptive statistics were used. Results A total of 24 RCTs (n = 11128 in total) were included. Placebo-treated patients (n = 3899) were mostly females (93.5%), Caucasians (60.2%), of mean age 39.7 years, and having a mean disease duration of 7.4 years. Their mean initial SLEDAI 2000 was 10.4, whereas 60.5% had positive anti-dsDNA antibodies, 41.9% low C3 and 35.6% low C4 at randomization. Standard-of-care treatment included glucocorticosteroids in 85.9%, antimalarials in 72.8% and immunosuppressives in 48.5%. The response to placebo was 36.2% for the primary end point (as defined in each study), 39.8% for the SLE Responder Index-4 (SRI-4), 29.2% for SRI-5, 28.4% for SRI-6 and 30.9% for BILAG-based Combined Lupus Assessment response. Regarding safety, there were serious adverse events in 16.3% of patients, serious infections in 5.5% and malignancies in 0.3%, and death occurred in 0.56% of patients. Conclusion More than one-third of the placebo-treated patients achieved their respective primary end points in RCTs with biologics in non-renal, non-neuropsychiatric SLE. The response rate was higher for certain end points, such as the SRI-4, while it decreased with more stringent end points.