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

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.

Impact of belimumab on patient-reported outcomes in systemic lupus erythematosus: review of clinical studies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune, multisystem rheumatic disease with significant impact on health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide valuable data on patient perceptions across a variety of domains, such as HRQoL, pain, fatigue, and depression. The measurement and results of PROs with respect to HRQoL in randomized controlled trials (RCTs) on belimumab (B-lymphocyte stimulator inhibitor) in SLE are reviewed here, including BLISS-52 and BLISS-76, as well as publications related to belimumab trials that included HRQoL data. Other trials that evaluated belimumab did not include HRQoL data and were therefore not included in the analysis. The BLISS-52 and BLISS-76 RCTs met their primary endpoints and demonstrated improvements in PROs, measured by the 36-item Short Form Health Survey, EuroQol 5 Dimensions, and Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Belimumab was shown overall to improve PROs in adult autoantibody-positive lupus patients.

Novel biological therapeutic approaches to cutaneous lupus erythematosus.

INTRODUCTION: Cutaneous lupus erythematosus (CLE) encompasses a spectrum of dermatologic manifestations which can occur with or without systemic lupus erythematosus (SLE). Treatment of CLE is challenging as the traditional treatments are off label and often fail and there is no drug specifically approved for CLE. The knowledge gained from the emerging trials on biologic therapy in SLE has provided insight into the utility of biologic therapy for CLE. AREAS COVERED: An overview is provided on the biological agents studied for CLE discussing their immunological target, their efficacy in treating the various CLE manifestations and the outcome measures used. EXPERT OPINION: There is a paucity of trials dedicated to the biologic treatment of CLE. Several of the described biological treatments' efficacy suggests that different clinical phenotypes of CLE may require different immunological targeted therapies. Recently published and ongoing trials of SLE focusing on novel agents for CLE using the Cutaneous Lupus Area and Severity Index (CLASI) as the outcome measure have shown promising results. Further trials designed specifically to study the efficacy of biologic treatment in CLE subgroups with or without systemic involvement using specific metrics for assessing cutaneous involvement are needed and will aid in illuminating the role of biologic therapy in CLE.