Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE)

Abstract Background To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. Methods Systematic review and meta-analysis following PRISMA guidelines. Data sources MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021. Study criteria Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. Data extraction: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias. Results Forty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes. Conclusion Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE