P Luthra1, L Peyrin-Biroulet2, A C Ford1,3. 1. Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK. 2. Inserm U954 and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-les-Nancy, France. 3. Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
Abstract
BACKGROUND: Anti-integrin antibodies are effective therapies for Crohn's disease (CD) and ulcerative colitis (UC). However, these drugs carry theoretical risks of opportunistic infection and malignancy. AIM: To pool data from all placebo-controlled studies, to estimate risk of opportunistic infection or malignancy with anti-integrin antibodies. METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched (up to December 2014). Randomised placebo-controlled trials of anti-integrin antibodies in adults with active or quiescent CD or UC were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection or malignancy, with 95% confidence intervals (CIs). RESULTS: The search strategy identified 1579 citations, 12 of which were eligible (four trials of natalizumab, six of vedolizumab and two of etrolizumab). The RR of developing an opportunistic infection was not significantly higher with non-gut specific (2.34; 95% CI 0.05-108.72) or gut specific anti-integrin antibodies (1.55; 95% CI 0.16-14.83). The RR was generally higher in trials of non-gut specific anti-integrin antibodies with duration of therapy ≥52 weeks (RR = 15.00; 95% CI 0.86-261), but remained non-significant. The RR of malignancy was not elevated with non-gut specific (1.57; 95% CI 0.19-12.74) or gut specific anti-integrin antibodies (0.78; 95% CI 0.15-4.02). CONCLUSIONS: Absolute numbers of opportunistic infections were higher with anti-integrin antibodies, but this difference is not statistically significant. There was no increased risk of malignancy detected. Long-term data in large prospective cohorts are needed to further assess this issue.
BACKGROUND: Anti-integrin antibodies are effective therapies for Crohn's disease (CD) and ulcerative colitis (UC). However, these drugs carry theoretical risks of opportunistic infection and malignancy. AIM: To pool data from all placebo-controlled studies, to estimate risk of opportunistic infection or malignancy with anti-integrin antibodies. METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched (up to December 2014). Randomised placebo-controlled trials of anti-integrin antibodies in adults with active or quiescent CD or UC were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection or malignancy, with 95% confidence intervals (CIs). RESULTS: The search strategy identified 1579 citations, 12 of which were eligible (four trials of natalizumab, six of vedolizumab and two of etrolizumab). The RR of developing an opportunistic infection was not significantly higher with non-gut specific (2.34; 95% CI 0.05-108.72) or gut specific anti-integrin antibodies (1.55; 95% CI 0.16-14.83). The RR was generally higher in trials of non-gut specific anti-integrin antibodies with duration of therapy ≥52 weeks (RR = 15.00; 95% CI 0.86-261), but remained non-significant. The RR of malignancy was not elevated with non-gut specific (1.57; 95% CI 0.19-12.74) or gut specific anti-integrin antibodies (0.78; 95% CI 0.15-4.02). CONCLUSIONS: Absolute numbers of opportunistic infections were higher with anti-integrin antibodies, but this difference is not statistically significant. There was no increased risk of malignancy detected. Long-term data in large prospective cohorts are needed to further assess this issue.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059