NOCEBO EFFECT ON DIARRHOEA REPORTED IN THE SENSCIS TRIAL OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD)

BackgroundUnfavourable effects observed after administration of placebo that may be attributed to factors such as expectation or conditioning are known as nocebo effects. Prior to initiation of the SENSCIS trial, diarrhoea was a known side-effect of nintedanib.ObjectivesTo investigate whether a nocebo effect contributed to reporting of diarrhoea in the SENSCIS trial.MethodsThe SENSCIS trial enrolled patients with systemic sclerosis (SSc) with first non-Raynaud symptom in the prior ≤7 years and ≥10% extent of fibrotic ILD on high-resolution computed tomography. Patients were randomised to receive nintedanib or placebo until the last patient had reached week 52 but for ≤100 weeks. A follow-up visit was conducted 28 days after the end of treatment. Adverse events were reported by investigators irrespective of causality and coded according to the Medical Dictionary for Regulatory Activities. We analysed the incidence of diarrhoea adverse events in the on-treatment period (i.e., events with onset between the first intake of trial drug intake and the last intake plus 7 days) and in the post-discontinuation period (i.e., events with onset between the first day after the on-treatment period and the end of the follow-up period) in the nintedanib and placebo groups. Incidence rates were calculated as the number of patients with diarrhoea adverse events divided by the time at risk.ResultsIn the on-treatment period (time at risk: 277.8 patient-years), the rate of diarrhoea adverse events in the placebo group (n=288) was 33.1 per 100 patient-years. In the post-discontinuation period (time at risk: 41.9 patient-years), the rate of diarrhoea adverse events in the placebo group (n=284) was 19.1 per 100 patient-years. In the on-treatment period (time at risk: 105.1 patient-years), the rate of diarrhoea adverse events in the nintedanib group (n=288) was 209.3 per 100 patient-years. In the post-discontinuation period (time at risk: 53.7 patient-years), the rate of diarrhoea adverse events in the nintedanib group (n=283) was 5.6 per 100 patient-years.ConclusionIn the SENSCIS trial in patients with SSc-ILD, the rate of diarrhoea adverse events in the placebo group fell after trial drug was discontinued. This suggests that a nocebo effect may have contributed to the diarrhoea adverse events reported in the SENSCIS trial.AcknowledgementsThe SENSCIS trial was funded by Boehringer Ingelheim. Oliver Distler, Kristin B Highland and Arata Azuma were members of the SENSCIS trial Steering Committee.Disclosure of InterestsOliver Distler Speakers bureau: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Speaker fee: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Consultancy fee: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and TopadurOD has/had relationships with the following companies in the area of potential treatments for arthritides in the last three calendar years:Consultancy fee: Abbvie, Grant/research support from: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Research Grants: Boehringer Ingelheim, Kymera, Mitsubishi Tanabe, Kristin Highland Speakers bureau: Actelion Pharmaceuticals (Jansen), Bayer Healthcare, Boehringer Ingelheim, United Therapeutics, Paid instructor for: Acceleron Pharmaceuticals, Actelion Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Gilead Sciences, United Therapeutics, Consultant of: Boehringer Ingelheim, Forsee Pharmaceuicals, Genentech, United Therapeutics, Grant/research support from: Acceleron Pharmaceuticals, Actelion Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Genentech, Gossamer Bio, Eiger Pharmaceuticlas, Lilly Pharmaceuticals, Reata Pharmaceuticals, United Therapeutics, Viela Bio (Horizon Pharmaceuticals), Arata Azuma Speakers bureau: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Consultant of: Boehringer Ingelheim, Kyorin Pharma, Taiho Co., Toray Medical Co., Grant/research support from: Boehringer Ingelheim, Taiho Co., Corinna Miede Employee of: Corinna Miede is an employee of mainanalytics GmbH that is contracted by Boehringer Ingelheim, Margarida Alves Employee of: Margarida Alves is an employee of Boehringer Ingelheim, Petros Sfikakis: None declared