Additional Improvements in Clinical Response From Adjuvant Biologic Response Modifiers in Adults With Moderate to Severe Systemic Lupus Erythematosus Despite Immunosuppressive Agents: A Systematic Review and Meta-analysis

The role of biologic disease-modifying drugs in patients with systemic lupus erythematosus (SLE) remains controversial. Following systematic review and meta-analysis protocol, we searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov in January 2017 to identify all studies of people with SLE treated with biologic response modifiers. We performed direct frequentist random effects meta-analyses, calculated pooled relative risk and number needed to treat to achieve an outcome in 1 patient (NNT) as reciprocal to statistically significant absolute risk difference, and graded the quality of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Seven meta-analyses, 33 publications of randomized controlled trials (RCTs), and 5 observational studies met inclusion criteria. All studies enrolled previously treated adults with moderate to severe SLE despite conventional immunosuppression. In patients with extrarenal SLE, adjunctive belimumab (10 mg/kg) increases the rates of clinical response (moderate quality evidence from 2 RCTs, 1125 patients, NNT = 8 [95% CI, 6–16]), whereas adjunctive rituximab or abatacept are ineffective. In adults with lupus nephritis, adjunctive rituximab (4000 mg, very-low-quality evidence from 1 RCT, 144 patients, NNT = 5 [95% CI, 3–18]), but not abatacept, improves renal function. Belimumab and rituximab do not increase the risk of serious intolerable adverse effects leading to treatment discontinuation. Rigerimod, blisibimod, sifalimumab, and anifrolumab show promising results in early RCTs, whereas epratuzumab and tabalumab have an unfavorable benefit-to-harm balance. In adults with moderate to severe SLE despite conventional immunosuppressive agents, adjunctive belimumab in extrarenal SLE and off-label rituximab in lupus nephritis may offer additional modest benefits.