Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies

Background: Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD. Objectives: To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects. Study design: Meta-analysis. Search methods: Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger’s test, and the trim and fill method were used to assess publication bias. Results: In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9–67.4) and 80.3% (95% CI 69.7–87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6–81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5–81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4–90.2%; skin, 52.5–80.6%; and liver, 41.8–71.8%. In cGVHD, the response rates were gastrointestinal, 30.1–70.4%; skin, 30.1–84.4%; lung, 27.0–83.0%; and mouth 3.5–98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications. Conclusions: Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.