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Therapeutic Advances in Gastroenterology
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Review: Efficacy and safety of adalimumab in Crohn's disease

Gary R. Lichtenstein

University of Pennsylvania School of Medicine Hospital of the University of Pennsylvania, 3rd Floor Ravdin Building 3400 Spruce Street Philadelphia, PA, USA, gary.lichtenstein{at}uphs.upenn.edu

Remo Panaccione

University of Calgary Faculty of Medicine Foothills Medical Centre Rm. 6D30, TRW Building 3280 Hospital Drive NW Calgary AB, Canada

Gordon Mallarkey

SAGE Publications Ltd, 1 Oliver's Yard, 55 city Road, London EC1Y 1SP, UK

Adalimumab (ADA) is a subcutaneously (SC) self-administered fully human Ig G1 monoclonal antibody directed against tumor necrosis factor alpha (TNF{alpha}). In the CLASSIC I dose-ranging trial, ADA was superior to placebo for inducing remission in patients with moderate-to-severe Crohn's disease (CD) naive to TNF{alpha} inhibitor therapy. In CLASSIC II, patients in remission following CLASSIC I maintained remission for up to 56 weeks while on ADA. In CHARM, approximately 40% of the 499 patients with moderate-to-severe CD who responded to ADA, maintained remission at 26 and 52 weeks, thus confirming long-term efficacy. ADA demonstrated steroid-sparing properties, beneficial effects in patients with perianal fistulas, and decreases in rates of hospitalization and surgery. Sub-group analyses demonstrated similar remission rates irrespective of concomitant immunosuppressive use or previous exposure to other TNF{alpha} inhibitor therapy. In the GAIN trial, 325 patients who had either lost response or become intolerant to infliximab (IFX) were randomized to recieve ADA induction therapy or placebo. In this difficult-to-treat patient population, 21% achieved remission and half demonstrated clinical benefit from ADA induction therapy. Injection site reactions may occur with SC ADA (2—5% of patients), which are generally less dramatic in nature than infusion reactions experienced with intravenous IFX. Immunogenicity occurs with all monoclonal antibodies; however, in the CD development program anti-ADA antibodies were detected at low rates (0.7 and 2.6% of patients in the CLASSIC I and CLASSIC II studies, respectively). Based on robust short- and long-term efficacy data from large randomized controlled trials and a favorable safety signal, ADA has become a key addition to the therapeutic armamentarium in the treatment of moderate-to-severe CD.

Key Words: Crohn's disease • TNF{alpha} inhibitors • adalimumab • infliximab

References

  • Abbott Laboratories (2008) Humira prescribing information. Available at: www.humira.com (accessed 4 March, 2008).
  • ACP. (2006) Anti-tumor necrosis factor antibody therapy for rheumatoid arthritis increases risk for serious infection and malignancy . ACP Journal Club 145: 65 .[Medline] [Order article via Infotrieve]
  • Bongartz, T., Sutton, A.J., Sweeting, M.J., Buchan, I., Matteson, E.L. and Montori, V. (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials . Jama 295: 2275-2285.[Abstract/Free Full Text]
  • Chung, J.H., van Stavern, G.P., Frohman, L.P. and Turbin, R.E. (2006) Adalimumab-associated optic neuritis . Journal of the Neurological Sciences 244: 133-136.
  • Clark, M., Colombel, J.F., Feagan, B.C., Fedorak, R.N., Hanauer, S.B., Kamm, M.A. et al. (2007) American Gastroenterological Association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease , June 21-23, 2006. Gastroenterology 133: 312-339.[CrossRef]
  • Colombel, J.F., Kamm, M.A., Schwart, D. et al. (2007a) Sustainability of adalimumab in fistula healing and response: 2 year data from CHARM and 12-month open-label extension follow-up study . Am J Gastroenterol 102(suppl 2): S497-S498.[CrossRef]
  • Colombel, J.F., Rutgeerts, P., Sandborn, W.J. et al. (2007b) Adalimumab safety in Crohn's disease patients: open-label maintenance following the GAIN and CHARM trials . Am J Gastroenterol 102(suppl 2): S496-S497.
  • Colombel, J., Sandborn, W.J., Rutgeerts, P., Enns, R., Hanauer, S.B., Panaccione, R. et al. (2007c) Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the charm trial . Gastroenterology 132: 52-65.[CrossRef][Medline] [Order article via Infotrieve]
  • De Bandt, M., Sibilia, J., Le Loët, X., Prouzeau, S., Fautrel, B., Marcelli, C. et al. (2005) Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey . Arthritis Res Ther 7: R545-R551.[CrossRef][Medline] [Order article via Infotrieve]
  • Feagan, B.G., Loftus, E.V., Kamm, M.A. et al. (2007a) Impact of steroid discontinuation on healthcare resource utilization in Crohn's disease . Am J Gastroenterol 102(suppl 2): S445-S446.
  • Feagan, B.G., Panaccione, R., Sandborn, W.J., D'haens, G.R., Schreiber, S., Rutgeerts, P.J. et al. (2007b) An evaluation of adalimumab on the risk of hospitalization in patients with Crohn's disease, data from charm . Gastroenterology 132: T1312 .
  • Hadziselimovic, F. (2008) Adalimumab induces and maintains remission in severe, resistant paediatric Crohn disease . J Pediatric Gastroenterol Nutrition 46: 208-211.
  • Hanauer, S.B., Feagan, B.G., Lichtenstein, G.R., Mayer, L.F., Schreiber, S., Colombel, J.F. et al. (2002) Maintenance infliximab for Crohn's disease: The Accent I randomised trial . Lancet 359: 1541-1549.[CrossRef][Medline] [Order article via Infotrieve]
  • Hanauer, S.B., D'Haens, G.R., Colombel, J.F. et al. (2006a) Sustained clinical remission in patients with moderate to severe Crohn's disease with adalimumab, regardless of anti-TNF history or concomitant immunosuppressant therapy Am J Gastroenterol 101: S457 (Abstract 1173).
  • Hanauer, S.B., Kamm, M.A., Colombel, J.F., et al. (2006b) Sustained steroid-free clinical remission in patients with moderate to severe Crohn's disease treated with adalimumab . Am J Gastroenterol 101: S460 (Abstract 1181).[CrossRef]
  • Hanauer, S.B., Sandborn, W.J., Rutgeerts, P., Fedorak, R.N., Lukas, M., Macintosh, D. et al. (2006c) Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: The Classic-I Trial . Gastroenterology 130: 323-332.[CrossRef][Medline] [Order article via Infotrieve]
  • Hinojosa, J., Gomollon, F., Garcia, S., Bastida, G., Cabriada, J.L., Saro, C. et al. (2007) Efficacy and safety of short-term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open-label, multicentre trial . Alimentary Pharmacology and Therapeutics 25: 409-418.[Medline] [Order article via Infotrieve]
  • Ho, G.-T., Smith, L., Aitken, S., Lee, H.M., Ting, T., Fennell, J. et al. (2008) The use of adalimumab in the management of refractory Crohn's disease . Alimentary Pharmacology and Therapeutics 24: 308-315.
  • Lichtenstein, G.R., Yan, S., Bala, M., Blank, M. and Sands, B.E. (2005) Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease . Gastroenterology 128: 862-869.[CrossRef]
  • Lichtenstein, G.R., Yan, S., Bala, M. and Hanauer, S. (2004) Remission in patients with Crohn's disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries . American Journal of Gastroenterology 99: 91-96.[CrossRef][Medline] [Order article via Infotrieve]
  • Luces, C., and Bodger, K. (2006) Economic burden of inflammatory bowel disease: a UK perspective . Expert Review of Pharmacoeconomics & Outcomes Research 6: 471-482.[CrossRef]
  • Mian, S. and Baron, H. (2005) Adalimumab, a novel anti-tumor necrosis factor-alpha antibody in a child with refractory Crohn's disease . Journal of Pediatric Gastroenterology and Nutrition 41: 357-359.[CrossRef][Medline] [Order article via Infotrieve]
  • Micromedex (2008a) DRUGDEX Evaluations: adalimumab. Available at: www.micromedex.com (accessed 4 March, 2008).
  • Micromedex (2008b) DRUGDEX Evaluations: infliximab. Available at: www.micromedex.com (accessed 4 March, 2008).
  • Papadakis, K.A., Shaye, O.A., Vasiliauskas, E.A., Ippoliti, A., Dubinsky, M.C., Birt, J. et al. (2005) Safety and efficacy of adalimumab (D2e7) in Crohn's disease patients with an attenuated response to infliximab . American Journal of Gastroenterology 100: 75-79.[CrossRef][Medline] [Order article via Infotrieve]
  • Peyrin-Biroulet, L., Laclotte, C. and Bigard, M.A. (2007) Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: An open-label study . Alimentary Pharmacology and Therapeutics 25: 675-680.[Medline] [Order article via Infotrieve]
  • Plevy, S. (2006) ACG 2006 - Current and emerging strategies in biologic therapy for IBD. Medscape. Available at: http://www.medscape.com/viewarticle/548406 (accessed 20 February, 2008).
  • Ramos-Casals, M., Brito-Zeron, P., Munoz, S., Soria, N., Galiana, D., Bertolaccini, L. et al. (2007) Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 Cases . Medicine 86: 242-251.[CrossRef][Medline] [Order article via Infotrieve]
  • Remicade (2007) Remicade prescribing information. Available at: www.remicade.com (accessed 4 March, 2008).
  • Rutgeerts, P., Diamond, R.H., Bala, M., Lichtenstein, G.R., Bao, W., Patel, K. et al. (2006) Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease . Gastrointestinal Endoscopy 63: 433-442.[CrossRef][Medline] [Order article via Infotrieve]
  • Rutgeerts, P., Feagan, B.G., Lichtenstein, G.R., Mayer, L.F., Schrieber, S., Colombel, J.F. et al. (2004) Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease . Gastroenterology 126: 402-413.[CrossRef][Medline] [Order article via Infotrieve]
  • Rutgeerts, P.J., Melilli, L.E., Li, J. and Pollack, P.F. (2006) Adalimumab maintains improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores over 1 year following the initial attainment of remission in patients with moderately to severely active Crohn's disease: results of the Classic II study . Gastroenterology 130: T1125 .
  • Sandborn, W.J., Hanauer, S., Loftus Jr, E.V., Tremaine, W.J., Kane, S., Cohen, R. et al. (2004) An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn's disease . American Journal of Gastroenterology 99: 1984-1989.[CrossRef][Medline] [Order article via Infotrieve]
  • Sandborn, W.J., Hanauer, S.B., Rutgeerts, P., Fedorak, R.N., Lulcas, M., Macintosh, D.G. et al. (2007) Adalimumab for maintenance treatment of Crohn's disease: results of the Classic II trial . Gut 56: 1232-1239.[Abstract/Free Full Text]
  • Sandborn, W.J., Rutgeerts, P., Enns, R., Hanauer, S.B., Colombel, J.F., Panaccione, R. et al. (2007a) Adalimumab induction therapy for Crohn disease previously treated with infliximab: A randomized trial . Ann Intern Med 146: 829-838.[Abstract/Free Full Text]
  • Sands, B.E., Anderson, F.H., Bernstein, C.N., Chey, W.Y., Feagan, B.G., Fedorak, R.N. et al. (2004) Infliximab maintenance therapy for fistulizing Crohn's disease . N Engl J Med 350: 876-885.[Abstract/Free Full Text]
  • Seiderer, J., Brand, S., Dambacher, J., Pfennig, S., Jurgens, M., Goke, B. et al. (2007) Adalimumab in patients with Crohn's disease - safety and efficacy in an open-label single centre study . Alimentary Pharmacology and Therapeutics 25: 787-796.[Medline] [Order article via Infotrieve]
  • Sorbera, L.A., Rabasseda, X., Castaner, R.M. (2001) Adalimumab . Drugs Future 26: 639-646.[CrossRef]
  • Thompson, H.C., Pesa, J.A., Zhao, N., Han, C., Rahman, M.I., Tang, B. et al. (2007) Maintenance therapy with infliximab reduces hospitalization and surgery in Crohn's disease . Am J Gastroenterol 102(suppl 2): S436 .
  • Youdim, A., Vasiliauskas, E.A., Targan, S.R., Papadakis, K.A., Ippoliti, A., Dubinsky, M.C. et al. (2004) A pilot study of adalimumab in infliximab-allergic patients . Inflammatory Bowel Diseases 10: 333-338.[CrossRef][Medline] [Order article via Infotrieve]

Therapeutic Advances in Gastroenterology, Vol. 1, No. 1, 43-50 (2008)
DOI: 10.1177/1756283X08092548
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