Original articleSystematic reviews and meta-analysesBiologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis
Section snippets
Methods
Our protocol11 is registered with an international prospective register of systematic reviews (PROSPERO). The work was performed in accordance with the Cochrane Handbook,12 the ISPOR network meta-analysis guidance,13, 14 and the preferred reporting items for systematic reviews and meta-analyses (PRISMA) extension statement for reporting of systematic reviews incorporating network meta-analyses.15
Search Results
A summary of the evidence search and selection process is shown in Figure 1 (flow diagram). Forty-one full-text publications31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 reported results of 46 RCTs. Two more studies72, 73 had their results posted at ClinicalTrials.gov, and 1 additional study was initially identified through ClinicalTrials.gov and later in full-text publication.74
Discussion
In this systematic review and meta-analysis of RCTs assessing biologics for adult patients with IBD, we synthesized evidence from 49 studies reporting the occurrence of infectious AEs and malignancies as a safety (secondary) end point; none of those were head-to-head comparisons of biologic therapies. To the best of our knowledge, this study is the most comprehensive meta-analysis on the topic.
Overall, we detected a significant 19% increase in the odds of developing any infection among patients
References (80)
- et al.
Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn’s disease: a network meta-analysis
Gastroenterology
(2015) - et al.
Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis
Mayo Clin Proc
(2014) - et al.
Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices—part 1
Value Health
(2011) - et al.
Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2
Value Health
(2011) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials
J Clin Epidemiol
(1997) - et al.
Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment failed
Gastroenterology
(2014) - et al.
Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis
Gastroenterology
(2014) - et al.
Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis
Gastroenterology
(2014) - et al.
Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis
Gastroenterology
(2014)
Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial
Gastroenterology
Adalimumab for the induction and maintenance of clinical remission in Japanese patients with Crohn’s disease
J Crohns Colitis
Certolizumab pegol for active Crohn’s disease: a placebo-controlled, randomized trial
Clin Gastroenterol Hepatol
Treatment of active Crohn’s disease with MLN0002, a humanized antibody to the alpha4beta7 integrin
Clin Gastroenterol Hepatol
Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE Trial
Gastroenterology
Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial
Gastroenterology
Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial
Gastroenterology
Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial
Gastroenterology
A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease
Gastroenterology
Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study
Gastroenterology
Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial
Lancet
Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease
Gastroenterology
Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial
Gastroenterology
Risk of new or recurrent cancer in patients with inflammatory bowel disease and previous cancer exposed to immunosuppressive and anti-tumor necrosis factor agents
Clin Gastroenterol Hepatol
Biologic agents for IBD: practical insights
Nat Rev Gastroenterol Hepatol
Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis
Ann Intern Med
Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study
BMJ
Infectious complications of TNF-α inhibitor monotherapy versus combination therapy with immunomodulators in inflammatory bowel disease: analysis of the Food and Drug Administration Adverse Event Reporting System
J Gastrointest Liver Dis
Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases
JAMA
Conceptual and technical challenges in network meta-analysis
Ann Intern Med
Demystifying trial networks and network meta-analysis
BMJ
Simultaneous comparison of multiple treatments: combining direct and indirect evidence
BMJ
The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations
Ann Intern Med
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
BMJ
On the criteria used for assessing the risk of bias in randomized trials included in systematic reviews and meta-analyses addressing adverse effects
Eur J Epidemiol
What to add to nothing? use and avoidance of continuity corrections in meta-analysis of sparse data
Stat Med
Statistical aspects of the analysis of data from retrospective studies of disease
J Natl Cancer Inst
Operating characteristics of a rank correlation test for publication bias
Biometrics
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Conflicts of interest These authors disclose the following: Gionata Fiorino has served as a consultant and advisory board member for MSD, Takeda, AbbVie, and Janssen. Laurent Peyrin-Biroulet has received consulting fees from Merck, Abbott, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Shire, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boehringer-Ingelheim, Lilly, Pfizer, and HAC-pharma and lecture fees from Merck, Abbott, Takeda, Janssen, Ferring, Norgine, Tillots, Vifor, Therakos, and HAC-pharma. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, Abbott Laboratories, Merck, UCB-pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Danone, Alpha Wasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson & Johnson. The remaining authors disclose no conflicts.