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Comparison of Infliximab and Adalimumab in Biologic-Naive Patients With Ulcerative Colitis: A Nationwide Danish Cohort Study

Published:November 29, 2016DOI:https://doi.org/10.1016/j.cgh.2016.11.024

      Background & Aims

      This study compares the effectiveness and safety of infliximab and adalimumab in biologic-naive patients with ulcerative colitis (UC), in a nationwide register-based propensity score–matched cohort study.

      Methods

      From 1719 adults with UC, between ages 15 and 75 years in Denmark treated with either infliximab or adalimumab as their first biologic agent, we compared rates of all-cause hospitalization, UC-related hospitalization, major abdominal surgery, and serious infections after a variable 2:1 propensity score matching, accounting for baseline clinical characteristics, disease severity, health care utilization, and use of UC-related medications.

      Results

      As compared with infliximab-treated patients, adalimumab-treated patients had higher rate of all-cause hospitalization (hazard ratio [HR], 1.84; 95% CI, 1.18–2.85) and a trend toward higher rate of UC-related hospitalization (HR, 1.71; 95% CI, 0.95–3.07), particularly in a stratum of patients on concomitant immunomodulator therapy. However, risk of abdominal surgery (HR, 1.35; 95% CI, 0.62–2.94) was not different between the 2 treatment groups. Risk of serious infection requiring hospitalization was significantly higher in adalimumab-treated patients (HR, 5.11; 95% CI, 1.20–21.80).

      Conclusions

      In this nationwide propensity score matched–cohort study of biologic-naive adults with UC, use of adalimumab as first-line biologic over infliximab was associated with higher risk of hospitalization and serious infections, although risk of surgery was not different. In the absence of head-to-head trials, this evidence may assist patients, health care providers, purchasers, and policy makers to make informed decisions that may improve health care in UC.

      Keywords

      Abbreviations used in this paper:

      CI (confidence interval), HR (hazard ratio), IBD (inflammatory bowel disease), ICD (International Classification of Diseases), TNF (tumor necrosis factor), UC (ulcerative colitis)
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      References

        • Nielsen O.H.
        • Ainsworth M.A.
        Tumor necrosis factor inhibitors for inflammatory bowel disease.
        N Engl J Med. 2013; 369: 754-762
        • Kornbluth A.
        • Sachar D.B.
        Practice Parameters Committee of the American College of G. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.
        Am J Gastroenterol. 2010; 105: 501-523
        • Sandborn W.J.
        • Rutgeerts P.
        • Feagan B.G.
        • et al.
        Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab.
        Gastroenterology. 2009; 137: 1250-1260
        • Feagan B.G.
        • Sandborn W.J.
        • Lazar A.
        • et al.
        Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis.
        Gastroenterology. 2014; 146: 110-118
        • Nestorov I.
        Clinical pharmacokinetics of TNF antagonists: how do they differ?.
        Semin Arthritis Rheum. 2005; 34: 12-18
        • Danese S.
        • Fiorino G.
        • Peyrin-Biroulet L.
        • et al.
        Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.
        Ann Intern Med. 2014; 160: 704-711
        • Singh S.
        • Garg S.K.
        • Wang Z.
        • et al.
        Letter: comparative efficacy of biological therapy in patients with ulcerative colitis.
        Aliment Pharmacol Ther. 2014; 39: 1432-1433
        • Singh S.
        • Heien H.C.
        • Sangaralingham L.R.
        • et al.
        Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis.
        Aliment Pharmacol Ther. 2016; 43: 994-1003
        • Sandborn W.J.
        • Sakuraba A.
        • Wang A.
        • et al.
        Comparison of real-world outcomes of adalimumab and infliximab for patients with ulcerative colitis in the United States.
        Curr Med Res Opin. 2016; 32: 1233-1241
        • Pedersen C.B.
        • Gotzsche H.
        • Moller J.O.
        • et al.
        The Danish Civil Registration System. A cohort of eight million persons.
        Dan Med Bull. 2006; 53: 441-449
        • Andersen T.F.
        • Madsen M.
        • Jorgensen J.
        • et al.
        The Danish National Hospital Register. A valuable source of data for modern health sciences.
        Dan Med Bull. 1999; 46: 263-268
        • Fonager K.
        • Sorensen H.T.
        • Rasmussen S.N.
        • et al.
        Assessment of the diagnoses of Crohn's disease and ulcerative colitis in a Danish hospital information system.
        Scand J Gastroenterol. 1996; 31: 154-159
        • Rungoe C.
        • Langholz E.
        • Andersson M.
        • et al.
        Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979–2011.
        Gut. 2014; 63: 1607-1616
        • Nyboe Andersen N.
        • Pasternak B.
        • Friis-Moller N.
        • et al.
        Association between tumour necrosis factor-alpha inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study.
        BMJ. 2015; 350: h2809
        • Beaugerie L.
        • Seksik P.
        • Nion-Larmurier I.
        • et al.
        Predictors of Crohn's disease.
        Gastroenterology. 2006; 130: 650-656
        • Singh S.
        • Heien H.C.
        • Sangaralingham L.R.
        • et al.
        Comparative effectiveness and safety of anti-tumor necrosis factor agents in biologic-naive patients with Crohn's disease.
        Clin Gastroenterol Hepatol. 2016; 14: 994-1003
        • Rassen J.A.
        • Shelat A.A.
        • Myers J.
        • et al.
        One-to-many propensity score matching in cohort studies.
        Pharmacoepidemiol Drug Saf. 2012; 21: 69-80
        • Deyo R.A.
        • Cherkin D.C.
        • Ciol M.A.
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619
        • Schneeweiss S.
        Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics.
        Pharmacoepidemiol Drug Saf. 2006; 15: 291-303
        • Laharie D.
        • Bourreille A.
        • Branche J.
        • et al.
        Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.
        Lancet. 2012; 380: 1909-1915
        • Osterman M.T.
        • Haynes K.
        • Delzell E.
        • et al.
        Comparative effectiveness of infliximab and adalimumab for Crohn's disease.
        Clin Gastroenterol Hepatol. 2014; 12: 811-817
        • Dotan I.
        • Ron Y.
        • Yanai H.
        • et al.
        Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study.
        Inflamm Bowel Dis. 2014; 20: 2247-2259
        • Sharma S.
        • Eckert D.
        • Hyams J.S.
        • et al.
        Pharmacokinetics and exposure-efficacy relationship of adalimumab in pediatric patients with moderate to severe Crohn's disease: results from a randomized, multicenter, phase-3 study.
        Inflamm Bowel Dis. 2015; 21: 783-792
        • Bultman E.
        • de Haar C.
        • van Liere-Baron A.
        • et al.
        Predictors of dose escalation of adalimumab in a prospective cohort of Crohn's disease patients.
        Aliment Pharmacol Ther. 2012; 35: 335-341
        • Seminerio J.L.
        • Koutroubakis I.E.
        • Ramos-Rivers C.
        • et al.
        Impact of obesity on the management and clinical course of patients with inflammatory bowel disease.
        Inflamm Bowel Dis. 2015; 21: 2857-2863
        • Flores A.
        • Burstein E.
        • Cipher D.J.
        • et al.
        Obesity in inflammatory bowel disease: a marker of less severe disease.
        Dig Dis Sci. 2015; 60: 2436-2445
        • Stabroth-Akil D.
        • Leifeld L.
        • Pfutzer R.
        • et al.
        The effect of body weight on the severity and clinical course of ulcerative colitis.
        Int J Colorectal Dis. 2015; 30: 237-242
        • Bhalme M.
        • Sharma A.
        • Keld R.
        • et al.
        Does weight-adjusted anti-tumour necrosis factor treatment favour obese patients with Crohn's disease?.
        Eur J Gastroenterol Hepatol. 2013; 25: 543-549
        • Andersen N.N.
        • Jess T.
        Risk of infections associated with biological treatment in inflammatory bowel disease.
        World J Gastroenterol. 2014; 20: 16014-16019