The role of prokinetics in managing gastrointestinal involvement in systemic sclerosis: a systematic literature review

Gastrointestinal involvement (GI) in systemic sclerosis (SSc) is frequent and heterogeneous, manifesting with different degrees of dysmotility. This systematic literature review aimed to summarize evidence on prokinetics for treating SSc-related GI dysmotility. Studies investigating the effects of prokinetic agents on GI function and/or GI symptoms in patients with SSc were systematically identified on PubMed and Embase. A qualitative data synthesis was conducted, given the (anticipated) wide heterogeneity in study designs, interventions, and outcomes. Twenty-one studies evaluating the effects of prokinetics in patients with SSc were included. Thirteen studies focused on GI motility using objective tests, eight assessed clinical responses, and six evaluated both. Cisapride (n = 5 studies), Metoclopramide (n = 7 studies), Octreotide (n = 4 studies), and Prucalopride (n = 1 study) were among the most studied prokinetics, with varying effects on different GI anatomical regions. While Metoclopramide consistently improved overall GI motility, other prokinetics provided selective benefits; Cisapride improved gastric emptying and colonic motility, but not esophageal motility, and Octreotide improved small bowel motility but delayed gastric emptying. Regarding symptomatic improvement, only prucalopride was evaluated using a validated patient questionnaire, showing improvement in both upper and lower GI symptoms. Prokinetic drugs may improve GI motility and symptoms in patients with SSc. There is an unmet need for future well-designed studies to refine patient stratification and optimize treatment outcomes.