Review article: steroid resistance in inflammatory bowel disease – mechanisms and therapeutic strategies

Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options.

[1]  B. Feagan,et al.  Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. , 2016, The Cochrane database of systematic reviews.

[2]  A. Akobeng Infliximab for induction and maintenance therapy for ulcerative colitis. , 2006, Journal of pediatric gastroenterology and nutrition.

[3]  S. Targan,et al.  Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial , 2006, Gut.

[4]  G. Porro,et al.  A rare cause of diuretic refractory ascites , 2005, Gut.

[5]  Paul Rutgeerts,et al.  Infliximab for induction and maintenance therapy for ulcerative colitis. , 2005, The New England journal of medicine.

[6]  M. Manns,et al.  Effects of azathioprine and its metabolites on repair mechanisms of the intestinal epithelium in vitro , 2005, Regulatory Peptides.

[7]  F. Ajayi,et al.  Delayed-Release Oral Mesalamine at 4.8 g/day (800 mg tablet) for the Treatment of Moderately Active Ulcerative Colitis: The ASCEND II Trial , 2005, The American Journal of Gastroenterology.

[8]  S. Schreiber,et al.  A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. , 2005, Gastroenterology.

[9]  P. Rutgeerts,et al.  Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. , 2005, The New England journal of medicine.

[10]  A. Cohen,et al.  Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. , 2005, The New England journal of medicine.

[11]  P. Marteau,et al.  An unusual cause of soft tissue infection , 2005, Gut.

[12]  Å. Danielsson,et al.  Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. , 2005, Gastroenterology.

[13]  S. Hanauer,et al.  Infliximab induction and maintenance therapy for ulcerative colitis: the ACT 2 trial , 2005 .

[14]  G. Corrao,et al.  Long-term oral plus topical mesalazine in frequently relapsing ulcerative colitis. , 2005, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[15]  D. Jewell,et al.  Oral methotrexate in ulcerative colitis , 2005, Alimentary pharmacology & therapeutics.

[16]  H. Drummond,et al.  Allelic variations of the multidrug resistance gene determine susceptibility and disease behavior in ulcerative colitis. , 2005, Gastroenterology.

[17]  M. Vieth,et al.  A double‐blind dose‐escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis , 2005, Alimentary pharmacology & therapeutics.

[18]  D. Jewell,et al.  Ciclosporin use in acute ulcerative colitis: a long-term experience , 2005, European journal of gastroenterology & hepatology.

[19]  S. Hanauer,et al.  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 , 2004, American Journal of Gastroenterology.

[20]  S. Travis Predicting outcome in severe ulcerative colitis. , 2004, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[21]  I. Adcock,et al.  Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. , 2004, The Journal of allergy and clinical immunology.

[22]  H. Tilg,et al.  A randomized placebo-controlled trial of pegylated interferon alpha in active ulcerative colitis , 2003 .

[23]  H. Tilg,et al.  A randomised placebo controlled trial of pegylated interferon α in active ulcerative colitis , 2003, Gut.

[24]  P. Rutgeerts,et al.  Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. , 2003, Gastroenterology.

[25]  P. Rutgeerts,et al.  Interferon β-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study , 2003 .

[26]  R. Playford,et al.  Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. , 2003, The New England journal of medicine.

[27]  I. S. Shaw,et al.  Basiliximab (anti‐CD25) in combination with steroids may be an effective new treatment for steroid‐resistant ulcerative colitis , 2003, Alimentary pharmacology & therapeutics.

[28]  A. Forbes,et al.  Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial , 2003, Gut.

[29]  B. Sands,et al.  Repifermin (keratinocyte growth factor‐2) for the treatment of active ulcerative colitis: a randomized, double‐blind, placebo‐controlled, dose‐escalation trial , 2003, Alimentary pharmacology & therapeutics.

[30]  E. Sternberg Faculty Opinions recommendation of A role for STAT5 in the pathogenesis of IL-2-induced glucocorticoid resistance. , 2003 .

[31]  S. Targan,et al.  A humanized anti-CD3 monoclonal antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase I study , 2003 .

[32]  A. Hawthorne Ciclosporin and refractory colitis. , 2003, European journal of gastroenterology & hepatology.

[33]  P. Rutgeerts,et al.  A Pilot Study on the Use of the Humanized Anti–Interleukin-2 Receptor Antibody Daclizumab in Active Ulcerative Colitis , 2003, American Journal of Gastroenterology.

[34]  R. Renkawitz,et al.  Molecular aspects of glucocorticoid hormone action in rheumatoid arthritis. , 2002, Cytokines, cellular & molecular therapy.

[35]  O. Paoluzi,et al.  Azathioprine or methotrexate in the treatment of patients with steroid‐dependent or steroid‐resistant ulcerative colitis: results of an open‐label study on efficacy and tolerability in inducing and maintaining remission , 2002, Alimentary pharmacology & therapeutics.

[36]  S. Hanauer,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[37]  I. Adcock,et al.  p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. , 2002, The Journal of allergy and clinical immunology.

[38]  R. Pounder,et al.  A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha‐4 integrin , 2002, Alimentary pharmacology & therapeutics.

[39]  R. Pounder,et al.  A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active crohn's disease , 2001 .

[40]  A. Zinsmeister,et al.  The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. , 2001, Gastroenterology.

[41]  R. Straub,et al.  Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis , 2001, Annals of the rheumatic diseases.

[42]  R. Löfberg,et al.  Glucocorticoid Receptor mRNA in Patients with Ulcerative Colitis: A Study of Responders and Nonresponders to Glucocorticosteroid Therapy , 2001, Inflammatory bowel diseases.

[43]  P. Munkholm,et al.  An open-labeled, randomized study comparing systemic interferon-α-2A and prednisolone enemas in the treatment of left-sided ulcerative colitis , 2001, American Journal of Gastroenterology.

[44]  K. Schulze-Osthoff,et al.  Molecular mechanisms of glucocorticoid resistance. , 2000, Gastroenterology.

[45]  K. Schulze-Osthoff,et al.  Abnormal activation of transcription factor NF-κB involved in steroid resistance in chronic inflammatory bowel disease , 2000, American Journal of Gastroenterology.

[46]  G. Greenberg,et al.  A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. , 2000, The New England journal of medicine.

[47]  J. Schwartz,et al.  Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma. , 2000, Gastroenterology.

[48]  T. Ashida,et al.  Expression of glucocorticoid receptor β in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis ☆ ☆☆ , 2000 .

[49]  S. Hearing,et al.  Audit of cyclosporin use in inflammatory bowel disease: limited benefits, numerous side‐effects , 2000, European journal of gastroenterology & hepatology.

[50]  S. Lightman,et al.  Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing. , 1999, The Journal of clinical endocrinology and metabolism.

[51]  C. Dayan,et al.  Wide variation in lymphocyte steroid sensitivity among healthy human volunteers. , 1999, The Journal of clinical endocrinology and metabolism.

[52]  C. Probert,et al.  Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes , 1999, Gut.

[53]  Williams,et al.  Immunosuppressive therapy for ulcerative colitis: results of a nation‐wide survey among consultant physician members of the British Society of Gastroenterology , 1999, Alimentary pharmacology & therapeutics.

[54]  A. Peña,et al.  Genetic markers in clinically well defined patients with ulcerative colitis (UC) , 1999 .

[55]  A. Peña,et al.  Genetic markers in clinically well defined patients with ulcerative colitis (UC). , 1998, Clinical and experimental immunology.

[56]  R. Löfberg,et al.  Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis , 1998, European journal of gastroenterology & hepatology.

[57]  K. Kaestner,et al.  DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival , 1998, Cell.

[58]  S. Targan,et al.  Safety and tolerance of rHuIL-10 treatment in patients with mild/moderate active ulcerative colitis , 1998 .

[59]  Y. Takasaki,et al.  Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. , 1998, Arthritis and rheumatism.

[60]  A. Lavy,et al.  Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. , 1997, The American journal of gastroenterology.

[61]  B. Groner,et al.  Functional interactions between Stat5 and the glucocorticoid receptor , 1996, Nature.

[62]  Julian R. E. Davis,et al.  Glucocorticoid receptor structure and function in glucocorticoid-resistant small cell lung carcinoma cells. , 1996, Cancer research.

[63]  A. Lavy,et al.  Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. , 1996, Gastroenterology.

[64]  T. Lee,et al.  Hypothalamic-pituitary-adrenal axis in corticosteroid-resistant bronchial asthma. , 1996, American journal of respiratory and critical care medicine.

[65]  M. Tattersall,et al.  Characteristics of cancer cell death after exposure to cytotoxic drugs in vitro. , 1996, British Journal of Cancer.

[66]  Joseph A. DiDonato,et al.  Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis , 1995, Science.

[67]  I. Adcock,et al.  Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. , 1995, Journal of immunology.

[68]  C. Bernstein,et al.  Selected summary: Feagan BG, McDonald JWD, Rochon J, et al. for the Canadian Crohn's Relapse Prevention Trial Investigators. Low-dose cyclosporine for the treatment of Crohn's disease. N Engl J Med 1994; 330:1846–1851 (June) , 1995 .

[69]  Loyd,et al.  Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. , 1995, The New England journal of medicine.

[70]  M. Karin,et al.  Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. , 1995, Science.

[71]  A. Laupacis,et al.  Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators. , 1994, The New England journal of medicine.

[72]  S. Hanauer,et al.  Cyclosporine in severe ulcerative colitis refractory to steroid therapy. , 1994, The New England journal of medicine.

[73]  P. Munkholm,et al.  Frequency of glucocorticoid resistance and dependency in Crohn's disease. , 1994, Gut.

[74]  S. Szefler,et al.  Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. , 1993, Journal of immunology.

[75]  Chakravarty Bj Predictors and the rate of medical treatment failure in ulcerative colitis , 1993 .

[76]  A. Brufsky,et al.  A mutation of the glucocorticoid receptor in primary cortisol resistance. , 1993, The Journal of clinical investigation.

[77]  D. Accili,et al.  Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. , 1993, The Journal of clinical endocrinology and metabolism.

[78]  B. Chakravarty Predictors and the rate of medical treatment failure in ulcerative colitis. , 1993, The American journal of gastroenterology.

[79]  A. Axon,et al.  Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. , 1992, BMJ.

[80]  E. Gelfand,et al.  Steroid-resistant asthma: immunologic and pharmacologic features. , 1992, The Journal of allergy and clinical immunology.

[81]  S. Szefler,et al.  Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. , 1991, The American review of respiratory disease.

[82]  A. B. Kay,et al.  Lymphocytes , 1991 .

[83]  T. Lee,et al.  Glucocorticoid receptor characteristics in monocytes of patients with corticosteroid-resistant bronchial asthma. , 1991, The American review of respiratory disease.

[84]  S. Detera-Wadleigh,et al.  The genomic structure of the human glucocorticoid receptor. , 1991, The Journal of biological chemistry.

[85]  K. Constantine,et al.  Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. , 1991, The Journal of clinical investigation.

[86]  Stephan Gebel,et al.  Antitumor promotion and antiinflammation: Down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone , 1990, Cell.

[87]  S N Rasmussen,et al.  A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. , 1989, The New England journal of medicine.

[88]  M C Willingham,et al.  Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[89]  E. Langhoff,et al.  RECIPIENT LYMPHOCYTE SENSITIVITY TO METHYLPREDNISOLONE AFFECTS CADAVER KIDNEY GRAFT SURVIVAL , 1986, The Lancet.

[90]  R. Evans,et al.  Primary structure and expression of a functional human glucocorticoid receptor cDNA , 1985, Nature.

[91]  A. House,et al.  Variable inhibition of mitogen-induced blastogenesis in human lymphocytes by prednisolone in vitro. , 1985, Transplantation proceedings.

[92]  H. Hodgson,et al.  CYCLOSPORIN IN ULCERATIVE COLITIS , 1984, The Lancet.

[93]  J. Lennard-jones,et al.  Controlled trial of azathioprine in chronic ulcerative colitis. , 1982, British medical journal.

[94]  S. Truelove,et al.  FURTHER EXPERIENCE IN THE TREATMENT OF SEVERE ATTACKS OF ULCERATIVE COLITIS , 1978, The Lancet.

[95]  J. Lennard-jones,et al.  A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. , 1978, Scandinavian journal of gastroenterology.

[96]  A. McKendrick,et al.  DENTAL CARIES AND SUGAR INTAKE , 1975, The Lancet.

[97]  B. Levin,et al.  A controlled trial of azathioprine in the management of chronic ulcerative colitis. , 1975, Gastroenterology.

[98]  D. Jewell,et al.  Azathioprine in Ulcerative Colitis: Final Report on Controlled Therapeutic Trial , 1974, British medical journal.

[99]  D. Jewell,et al.  Intensive intravenous regimen for severe attacks of ulcerative colitis. , 1974, Lancet.

[100]  S. Truelove,et al.  Cortisone in Ulcerative Colitis , 1954 .