AB0658 Nocebo effect on diarrhoea reported in the SENSCIS trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) | Annals of the Rheumatic Diseases

Abstract

Background: Unfavourable 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. Objectives: To investigate whether a nocebo effect contributed to reporting of diarrhoea in the SENSCIS trial. Methods: The SENSCIS trial enrolled patients with systemic sclerosis (SSc) with frst non‐Raynaud symptom in the prior ≤7 years and ≥10% extent of fbrotic 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 frst 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 frst 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. Results: In 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. Conclusion: In 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.