P681 Systematic review and meta-analysis of the safety and efficacy of intra-fistular injections of mesenchymal stem cells in clinical trials and observational cohort studies

Abstract

Background: Perianal fistulas in patients with Crohn's disease (CD) is a stressful condition for both patients who suffer from pain, discharge and poor quality of life, and clinicians who face high rates of non-response and relapse with the available therapeutic armamentarium. Local injection of mesenchymal stem cells (MSC) has yielded promising results in this challenging condition. We conducted a systematic review and meta-analysis of all clinical trials and observational cohort studies to establish the safety and efficacy of local administration of MSCs for the treatment of perianal fistulas in CD patients. Methods: The PRISMA (P) statement was used for both planning and reporting. MEDLINE, EMBASE, Web of Science, Cochrane, CINAHL, ClinicalTrial.gov and the ECCO 2017 proceedings were searched for observational cohort studies, one arm and randomised clinical trial (RCT) through May 15, 2017. Safety was assessed as acute local and systemic events (pain, bleeding, infusional toxicity, fever, thromboembolism), organ system complications, infection, and long-term events (death, malignancy). The efficacy endpoint was evaluated in terms of clinical and/or radiologic closure of fistula tracks. Rates and relative risks (RRs) were pooled for safety and efficacy endpoints according to the Der Simonian and Laird random effects models with 95% confidence intervals (CI) computed. Results: A total of 345 citations were reviewed and 23 studies (3 substudies) met inclusion criteria. A total of 663 participants were evaluated. Four studies were RCTs and enrolled a total of 483 patients. At metanalysis, clinical response occurred in 80% (95% CI 70-89) of MSC treated patients (18 studies). In RCTs, this rate was 64% (95% CI 57-70) in the MSC and 37% (95% CI 21-55) in the placebo arms, RR 1.54 (95% CI 1.03-2.29). Radiologic response occurred in 83% (95% CI 65-96) of MSC-treated patients (7 studies, of which only 1 RCT). The cumulative adverse event (AE) rate was 53% (95% CI 30-75) in MSC-treated patients (17 studies). In RCTs it was 71% (95% CI 35-96) in the MSC and 66% (95% CI 38-89) in the control arm, RR=1.06 (95% CI 0.93-1.21). Treatment-related AEs occurred in 1% (95% CI 0-7) of MSC-treated patients (12 studies). In RCTs treatment-related AEs (e.g. anal abscess and pain) occurred in 13% (95% CI 5-24) in the MSC and 24% (95% CI 14-35) in the control arm, RR 0.65 (95% CI 0.44-0.98). No deaths occurred. Conclusions: Based on the current state-of-the-art, local administration of MSCs appears safe and efficacious. Limited large-scale controlled studies exist; further clinical trials with rigorous reporting of endpoints are required to ensure the correct positioning of this new therapeutic tool in the management of perianal CD.