Multiple treatment comparison in narcolepsy: a network meta-analysis.

Study Objectives: Randomized controlled trials (RCTs) that compared the safety and efficacy of medical treatments for narcolepsy were analyzed using network meta-analysis. Methods: The RCTs in narcolepsy were searched. Network meta-analysis compared efficacy and safety of multiple treatments, multi-arm studies, and multi-criteria treatment decisions, based on a random model that assumed heterogeneity between studies, with corrections for multi-arm studies. Results: Fourteen RCTs, three drug treatments, and six doses were identified: sodium oxybate (6 and 9 g/d), modafinil (between 200 and 400 mg/d), and pitolisant (up to 20 and up to 40 mg/d). Significant heterogeneity (>50%) between studies was found in 12/14 studies for almost all endpoints, but between-design consistency was present. For ESS and MWT, sodium oxybate 9 g/d, modafinil, and pitolisant up to 40 mg/d had similar efficacy. Pitolisant 40 mg/d and sodium oxybate 9 g/d in two nightly doses had similar efficacy in reducing cataplexy. A good safety profile characterized by a TEAE incidence risk ratio (IRR) <1.5 was found for all the compared treatments, except for sodium oxybate 9 g/d. Although no significant difference was found, Pitolisant 40 mg was shown with the best P scores for the benefit/risk (BR) ratio. Conclusions: Modafinil (200-400 mg/d), sodium oxybate 9 g/d, and pitolisant up to 40 mg/d had similar efficacy in reducing excessive day time sleepiness. Only sodium oxybate 9 g/d and pitolisant up to 40 mg/d were shown with a comparable beneficial effect on cataplexy. Overall, Pitolisant was found with the best P score on the BR ratio. Clinical Trial Registration: PROSPERO 2017 CRD42017054686. Efficacy, safety, and benefit-risk comparison of alternative treatments in narcolepsy: a network multiple comparisons of treatment meta-analysis. http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017054686.