Localized scleroderma (LS) is a rare chronic immune-mediated skin condition of unknown etiology characterized by an inflammatory response in the skin and subcutaneous tissues resulting in collagen deposition and subsequent fibrosis. There is no cure for LS. No therapies have been licensed specifically for the treatment of LS and the clinical management of the disease remains largely empirical. Abatacept, a recombinant fusion protein interfering with the T-cell costimulatory pathway, has been reported to be effective in adult cases of LS. We report the successful use of abatacept in a juvenile localized scleroderma (jLS) cohort and conduct a systematic literature review to evaluate the evidence supporting the use of abatacept in the treatment of LS.
We compiled retrospectively the clinical data on 8 cases of jLS that were treated with abatacept in our academic center. A systematic review protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) guidelines and has been registered with the international prospective register of systematic reviews (PROSPERO). Standardized searches of MEDLINE/PubMed and EMBASE were undertaken to identify studies reporting the use of abatacept in the treatment of LS. Heterogeneity in study design, interventions and reported outcomes necessitated a qualitative data synthesis.
The use of abatacept was effective and safe in our cohort of jLS patients. Our standardized searches identified 30 articles, of which 3 deemed eligible for full data extraction. All 3 studies were small (total of 18 patients; mean 6 subjects per study), single center, open-label, uncontrolled and non-randomized. The Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS) identified high risk-of bias for confounding variables and blinding of assessors in each of the 3 studies evaluated and in our pediatric case series.
The evidence-base to support the use of abatacept in the treatment of LS is currently limited and clinical practice guidelines should take a measured approach to such recommended therapy. Nonetheless, as the empirical evidence on the clinical effectiveness of abatacept in the treatment of LS accumulates, a double-blind placebo-controlled randomized clinical trial is necessary to formally evaluate the observations documented by case-based reports.