What Have We Learnt About the Treatment of Juvenile-Onset Systemic Lupus Erythematous Since Development of the SHARE Recommendations 2012?

Introduction: Juvenile-onset systemic lupus erythematous (JSLE) is a rare multisystem autoimmune disorder. In 2012, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative developed recommendations for the diagnosis/management of JSLE, lupus nephritis (LN) and childhood-onset anti-phospholipid syndrome (APS). These recommendations were based upon available evidence informing international expert consensus meetings. Objective: To review new evidence published since 2012 relating to the management of JSLE, LN and APS in children, since the original literature searches informing the SHARE recommendations were performed. Method: MEDLINE, EMBASE and CINAHL were systematically searched for relevant literature (2012-2021) using the following criteria: (1) English language studies; (2) original research studies regarding management of JSLE, LN, APS in children; (3) adult studies with 3 or more patients <18-years old, or where the lower limit of age range ≤16-years and the mean/median age is ≤30-years; (4) randomized controlled trials (RCTs), cohort studies, case control studies, observational studies, case-series with >3 patients. Three reviewers independently screened all titles/abstracts against predefined inclusion/exclusion criteria. All relevant manuscripts were reviewed independently by at least two reviewers. Data extraction, assessment of the level of evidence/methodological quality of the manuscripts was undertaken in-line with the original SHARE processes. Specific PUBMED literature searches were also performed to identify new evidence relating to each existing SHARE treatment recommendation. Results: Six publications met the inclusion/exclusion criteria for JSLE: three RCTs, one feasibility trial, one case series. For LN, 16 publications met the inclusion/exclusion criteria: eight randomized trials, three open label prospective clinical trials, five observational/cohort studies. For APS, no publications met the inclusion criteria. The study with the highest evidence was an RCT comparing belimumab vs. placebo, including 93 JSLE patients. Whilst the primary-endpoint was not met, a significantly higher proportion of belimumab-treated patients met the PRINTO/ACR cSLE response to therapy criteria. New evidence specifically addressing each SHARE recommendation remains limited. Conclusion: Since the original SHARE literature searches, undertaken >10-years ago, the main advance in JSLE treatment evidence relates to belimumab. Additional studies are urgently needed to test new/existing agents, and assess their long-term safety profile in JSLE, to facilitate evidence-based practice.