Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.
BACKGROUND
Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome.


OBJECTIVE
To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis.


METHODS
We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis.


RESULTS
A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC.


CONCLUSIONS
Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.
Department of Internal Medicine, Montefiore Medical Center, New York, NY, USA.
A
A
Cholapranee
Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.|McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
G S
GS
Hazlewood
Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
G G
GG
Kaplan
Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre, France.
L
L
Peyrin-Biroulet
Gastroenterology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA.
A N
http://orcid.org/0000-0002-9436-1821
AN
Ananthakrishnan
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001685:Biological Factors / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D009092:Mucous Membrane / Q000187:drug effects* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D001685:Biological Factors; D001688:Biological Products; D007166:Immunosuppressive Agents