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

Abstract

IntroductionJuvenile-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.ObjectiveTo 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.MethodMEDLINE, 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.ResultsSix 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.ConclusionSince 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.

Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force

“…The SHARE recommendations on the diagnosis and treatment of cSLE,33 LN31 and APS32 were considered during both the Delphi and consensus stages of this project. Where particular SHARE recommendations linked to a cSLE T2T overarching principle or point-to-consider this is detailed below, along with any new evidence since 2013 when the SHARE literature searches were completed (review of new evidence published separately34). Broadly, the SHARE recommendations relating to standardised disease activity/damage assessment, follow-up frequency, growth, renal biopsies, treatment of LN, tapering of glucocorticoids, escalation of DMARDS, APS and hydroxychloroquine were all of relevance to the overarching principles and points-to-consider for T2T in cSLE 31–33…”

“…Searches were updated to capture new evidence arising. 34 Provisional overarching principles and points-to-consider for T2T in cSLE were formulated by the steering committee, considering literature on: (A) targeted therapeutic approaches in cSLE and aSLE; (B) the SHARE recommendations [31][32][33] ; (C) new evidence published since the SHARE literature searches 34 ; (D) aSLE T2T recommendations 21 and (E) JIA T2T recommendations. 24 These were sent to the Task Force as part of two Delphi surveys (1a/1b).…”

“…The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative published recommendations for the diagnosis and management of cSLE in 2017, based on systematic literature searches performed in 2013,31–33 involving some Task Force members (MWB, SSMK, DS-M, TA, CAP, AR). Searches were updated to capture new evidence arising 34…”

Current views on lupus in children

“…Although MMF plays a more central role in the treatment of jSLE and B-cell-targeted treatments are adopted into the treatment of patients with severe disease, additional studies are needed to test new/ existing agents, and assess their long-term safety profile in jSLE, to facilitate evidence-based practice [93]. [96].…”

Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope

“…European recommendations for the diagnosis and management of lupus and LN in children and young people were developed as part of the Single Hub and Access Point for Paediatric Rheumatology in Europe (SHARE) initiative and published in 2017 [ 6 , 7 ]. These recommendations have provided an important basis for evidence-informed, consensus-led guidance to paediatricians but, similar to adult-onset SLE, additional evidence has subsequently emerged and updated guidelines are also warranted [ 8 ]. A whole life course approach guideline by BSR for other conditions, e.g.…”