Abstract
Purpose
The aim of this study was to evaluate the efficacy and safety of adalimumab (ADA) for Crohn’s disease.
Methods
Electronic databases, including PubMed, Embase, the Cochrane Library, and the Science Citation Index, were searched to retrieve relevant trials. We estimated pooled estimates of the odds ratio (OR) and relevant 95 % confidence interval (CI) using fixed effects model or random effects model as appropriate.
Results
Six randomized placebo-controlled studies met the selection criteria. Short-term clinical response/remission and long-term remission were better in the ADA groups than in the control groups (P < 0.05), both in anti-TNF-naive patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). And ADA was also effective for patients who were previously treated with IFX, and its efficacy in infliximab-exposed patients was probably less than in infliximab-naive patients. In patients with active Crohn’s disease (CD), ADA therapy was more effective than placebo for obtaining complete fistula closure. In comparison with placebo, ADA does not increase the risk of serious adverse events.
Conclusions
ADA appears to be effective in achieving short-term clinical response/remission, long-term remission, and complete fistula healing in CD, including patients not manageable with IFX, and appears to have a favorable safety profile. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of ADA in CD.
Similar content being viewed by others
References
Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640
Cassinotti A, Ardizzone S, Porro GB (2008) Adalimumab for the treatment of Crohn’s disease. Biologics 2:763–777
Juan J, Estiarte R, Colome E et al (2003) Burden of illness of Crohn’s disease in Spain. Dig Liver Dis 35:853–861
Molodecky NA, Soon IS, Rabi DM et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54
Shivananda S, Lennard-Jones J, Logan R et al (1996) Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut 39:690–697
Pajares JM, Gisbert JP (2001) Epidemiology of inflammatory bowel disease in Spain. A systematic review. Rev Esp Enferm Dig 93:9–20
Saro Gismera C, Lacort Fernandez M, Arguelles Fernandez G et al (2000) Incidenciay prevalencia de la enfermedad inflama-toria intestinal en Gijo’ n, Asturias, Espa-n˜ a. Gastroenterol Hepatol 23:322–327
Zeng Z, Zhu Z, Yang Y et al (2013) Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study. J Gastroenterol Hepatol 28:1148–1153
Shin DH, Sinn DH, Kim YH et al (2011) Increasing incidence of inflammatory bowel disease among young men in Korea between 2003 and 2008. Dig Dis Sci 56:1154–1159
Sood A, Midha V, Sood N et al (2003) Incidence and prevalence of ulcerative colitis in Punjab, North India. Gut 52:1587–1590
Yao T, Matsui T, Hiwatashi N (2000) Crohn’s disease in Japan: diagnostic criteria and epidemiology. Dis Colon Rectum 43(Suppl):S85–S93
Wilkins T, Jarvis K, Patel J (2011) Diagnosis and management of Crohn’s disease. Am Fam Physician 84:1365–1375
Ardizzone S, Bianchi Porro G (2005) Biologic therapy for inflammatory bowel disease. Drugs 65:2253–2286
Peyrin-Biroulet L, Deltenre P, de Suray N et al (2008) Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 6:644–653
Van Assche G, Vermeire S, Rutgeerts P (2010) The potential for disease modification in Crohn’s disease. Nat Rev Gastroenterol Hepatol 7:79–85
D’ Haens G, Van Deventer S, Van Hogezand R et al (1999) Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology 116:1029–1034
D’ Haens G, Noman M, Baert F et al (2002) Endoscopic healing after infliximab treatment for Crohn’s disease provides a longer time to relapse. Gastroenterology 122(Suppl 4):A-618
Cassinotti A, Travis S (2009) Incidence and clinical significance of immunogenicity to infliximab in Crohn’s disease: a critical systematic review. Inflamm Bowel Dis 15:1264–1275
Baert F, Noman M, Vermeire S et al (2003) Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 348:601–608
Hanauer SB, Wagner CL, Bala M et al (2004) Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2:542–553
Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D et al (2006) Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 130:323–333, quiz 591
Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Colombel JF, Panaccione R et al (2007) Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med 146:829–838
Watanabe M, Hibi T, Lomax KG, Paulson SK, Chao J, Alam MS et al (2012) Adalimumab for the induction and maintenance of clinical remission in Japanese patients with Crohn’s disease. J Crohn’s Colitis 6:160–173
Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R et al (2007) Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 132:52–65
Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF et al (2012) Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology 142(1102–1111):e2
Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh DG et al (2007) Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut 56:1232–1239
Colombel JF, Schwartz DA, Sandborn WJ, Kamm MA, D’Haens G, Rutgeerts P et al (2009) Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut 58:940–948
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M et al (1998) Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 352:609–613
Dewint P, Hansen BE, Verhey E et al (2014) Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn’s disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut 63:292–299
Present DH, Rutgeerts P, Targan S et al (1999) Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 340:1398–1405
Targan SR, Hanauer SB, van Deventer SJ et al (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 337:1029–1035
Behm BW, Bickston SJ (2008) Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev: CD006893
Abreu MT (2007) Crohn’s disease in patients who fail infliximab therapy: what does the future hold? Rev Gastroenterol Disord 7(Suppl 1):S20–S26
Hanauer SB, Feagan BG, Lichtenstein GR et al (2002) Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 359:1541–1549
Fichera A, Michelassi F (2007) Surgical treatment of Crohn’s disease. J Gastrointest Surg Off J Soc Surg Aliment Tract 11:791–803
Barthel HR, Gille T, Halbsguth A et al (2005) Successful treatment with adalimumab in infliximab-resistant Crohn’s disease. J Gastroenterol Hepatol 20:1464–1465
Colombel JF, Rutgeerts PJ, Sandborn WJ et al (2014) Adalimumab induces deep remission in patients with Crohn’s disease. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 12:414–422, e5
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Supplemental material
Below is the link to the electronic supplementary material.
Fig. 1
The forest plot of short-term clinical remission owing to ADA for the treatment of CD (GIF 26 kb)
Fig. 2
The effect of ADA compared with placebo on complete fistula closure (GIF 22 kb)
Fig. 3
The forest plot of long-term efficacy of ADA in patients previously treated with IFX compared with placebo (GIF 21 kb)
Fig. 4
The forest plot of adverse reactions with regard to the use of ADA for the treatment of CD (GIF 27 kb)
Rights and permissions
About this article
Cite this article
Song, YN., Zheng, P., Xiao, JH. et al. Efficacy and safety of adalimumab for the Crohn’s disease: a systematic review and meta-analysis of published randomized placebo-controlled trials. Eur J Clin Pharmacol 70, 907–914 (2014). https://doi.org/10.1007/s00228-014-1702-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-014-1702-1