Preliminary safety and efficacy profile of prucalopride in the treatment of systemic sclerosis (SSc)-related intestinal involvement: results from the open label cross-over PROGASS study

BACKGROUND: Prokinetics are used to treat enteric dismotility symptoms in systemic sclerosis (SSc) patients, but they often lack adequate efficacy. The most effective prokinetics belonging to the serotonin (5-HT(4)) receptor agonists class were withdrawn due to cardiac toxicity in relation to modest 5-HT(4) receptor affinity. Prucalopride is a high-affinity 5-HT(4) receptor agonist with no major cardiac issues, for which the efficacy in SSc has not yet been assessed. METHODS: Forty patients with self-reported mild to moderately severe enteric symptoms were enrolled in a cross-over 2 × 2 study. Subjects were randomized 1:1 to prucalopride 2 mg/day or no treatment for one month and vice versa after a 2-week washout period. Before and after each sequence the patients compiled the University of California Los Angeles gastrointestinal tract (UCLA GIT) 2.0 questionnaire and the numbers of complete intestinal movements were recorded. Oro-cecal transit time (OCTT) was evaluated by lactulose breath test in a subgroup of patients. Data were evaluated by mixed linear models corrected for the number of laxatives used during the study periods. RESULTS: There were 29 subjects who completed the study; 7 subjects withdrew due to side-effects and 4 subjects were not compliant with the study procedures. As compared to dummy treatment, prucalopride was associated with more intestinal evacuations (p < 0.001), improvement of UCLA GIT constipation (-0.672 ± 0.112 vs 0.086 ± 0.115; p < 0.001), reflux (-0.409 ± 0.094 vs 0.01 ± 0.096; p < 0.005) and bloating (-0.418 ± 0.088 vs -0.084 ± 0.09; p = 0.01) scores. Treatment was ranked moderately to more than moderately effective by 22 patients (72.4%). OCTT was significantly reduced during prucalopruide consumption (prucalopride: -20.1 ± 20.1 vs no treatment: 45.8 ± 21.3 minutes; treatment effect = -65.9 minutes; p = 0.035). CONCLUSIONS: The safety profile of prucalopride in SSc is similar to what is known from the literature. In patients with mild to severe gastrointestinal problems, prucalopride may be effective in treating dismotility symptoms, increasing the number of complete bowel movements and improving bowel transit, reducing reflux disease and bloating. TRIAL REGISTRATION: EU Clinical Trial Registry, EudraCT2012-005348-92. Registered on 19 February 2013.