Randomised placebo-controlled trials are the gold standard to assess new drugs in ulcerative colitis and Crohn’s disease, inflammatory bowel diseases which affect up to 1% of the European population. Farknot Architect via Getty Images Led by Dr Shahida Din, an honorary Senior Clinical Lecturer affiliated with the IGC, the researchers performed a systematic review of randomised placebo-controlled trials for the induction of remission in adults with moderately to severely active ulcerative colitis or luminal Crohn’s disease, which reported data on adverse events over a minimum treatment period of four weeks. Serious adverse events are defined as any adverse event that results in death, is life-threatening, requires admission to hospital or prolongation of an existing hospitalisation, or results in persistent or significant incapacity or disability.The search identified 47 trials, including 20,987 patients (with 68% receiving an active drug and 32% receiving a placebo), which were eligible. The risk of any treatment-emergent adverse event was no different with the active drug than with a placebo - 53·7% patients on the active drug versus 55·9% on the placebo. However, the risks of the worsening of IBD activity, withdrawal due to an adverse event, serious adverse event, serious infection, serious worsening of IBD activity, or venous thromboembolic events (VTEs), were all significantly lower with the active drug than the placebo.The number of people who would need to be treated with an active drug to avoid these potentially serious adverse events ranged from 23 for the worsening of IBD activity to 452 for VTEs. Only 27 randomised controlled trials were judged as being of low risk of bias across all domains. In a separate study, the researchers looked at whether these harms are also apparent with a placebo during the maintenance of remission trials in IBD over a period of 20 weeks or more. In this review, the search identified 45 trials including 16,562 patients – with just over 62% were receiving the active drug and just under 38% on the placebo - which were eligible.Again, the researchers found in the maintenance of remission trials in IBD, the placebo was associated with some clinically significant potential harms. Our research shows there might be risks associated with receiving a placebo, reflecting undertreated active IBD. The harms associated with placebos were likely due to a lower risk of adverse outcomes in patients receiving an active drug, rather than a true increase in the risk associated with receiving a placebo. Patients should be counselled about these potential harms before participating in clinical trials and alternative trial designs to mitigate these harms by minimising placebo exposure should be considered.” Dr Shahida Din Honorary Senior Clinical Lecturer Links Read the first study in The Lancet Gastroenterology & Hepatology Read the second study in The Lancet Gastroenterology & Hepatology Listen to a podcast translating the findings for patients Image credit: Farknot Architect via Getty Images Tags 2024 Publication date 25 Nov, 2024
