Methotrexate as a steroid sparing agent for asthma in adults.

BACKGROUND Sustained oral corticosteroid use can lead to complications, so there is interest in identifying agents that can reduce oral steroid use in people with asthma. Methotrexate has attracted attention as a possible steroid sparing agent in patients with chronic oral steroid dependent asthma. OBJECTIVES The objective of this review was to assess the effects of adding methotrexate to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids. SEARCH STRATEGY The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA Randomised trials of the addition of methotrexate compared with placebo in adult steroid dependent asthmatics. Duration of therapy needed to be at least 12 weeks. DATA COLLECTION AND ANALYSIS Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS Ten trials involving a total of 185 people were included. Study design and quality, corticosteroid dosages and outcomes varied widely. There was a reduction in oral corticosteroid dose favouring methotrexate in parallel trials (weighted mean difference -4.1 mg per day, 95% confidence interval -6.8 to -1.3) and also in cross-over trials (weighted mean difference -2.9 mg per day, 95% confidence interval -5.9 to -0.2). There was no difference between methotrexate and placebo for forced expiratory volume in one minute (weighted mean difference 0.12 litre, 95% confidence interval -0.21 to 0.45). Hepatotoxicity was a common adverse effect with methotrexate compared to placebo (odds ratio 6.9, 95% confidence interval 3.1 to 15.5). REVIEWER'S CONCLUSIONS Methotrexate may have a small steroid sparing effect in adults with asthma who are dependent on oral corticosteroids. However, the overall reduction in daily steroid use is probably not large enough to reduce steroid-induced adverse effects. This small potential to reduce the impact of steroid side-effects is probably insufficient to offset the adverse effects of methotrexate.

[1]  M. Krasna.  Minimally invasive staging for esophageal cancer. , 1997, Chest.

[2]  M. G. Marin.  Low-dose methotrexate spares steroid usage in steroid-dependent asthmatic patients: a meta-analysis. , 1997, Chest.

[3]  S. Szefler,et al.  Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. , 1997, The European respiratory journal.

[4]  J. Lynch,et al.  Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. , 1997, American journal of respiratory and critical care medicine.

[5]  D. Ledford.  TREATMENT OF STEROID-RESISTANT ASTHMA , 1996, Radiologic Clinics of North America.

[6]  R. Shiner,et al.  A Risk-Benefit Assessment of Methotrexate in Corticosteroid-Dependent Asthma , 1996, Drug safety.

[7]  T. Aldrich,et al.  Single, high-dose intramuscular triamcinolone acetonide versus weekly oral methotrexate in life-threatening asthma: a double-blind study. , 1995, American journal of respiratory and critical care medicine.

[8]  A. Stanziola,et al.  Long-term treatment with methotrexate in patients with corticosteroid-dependent bronchial asthma. , 1995, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[9]  R. Moss.  Alternative pharmacotherapies for steroid-dependent asthma. , 1995, Chest.

[10]  M. Weinblatt.  Methotrexate for chronic diseases in adults. , 1995, The New England journal of medicine.

[11]  R. Lockey,et al.  Comparison of oral pulse methotrexate with placebo in the treatment of severe glucocorticosteroid-dependent asthma. , 1994, The Journal of allergy and clinical immunology.

[12]  R. Shiner,et al.  Methotrexate in steroid‐dependent asthma: long‐term results , 1994, Allergy.

[13]  S. R. Wang,et al.  The inhibitory effect of methotrexate on PAF-induced neutrophil and eosinophil locomotion in asthmatic patients. , 1994, Asian Pacific journal of allergy and immunology.

[14]  G. Cott.  Current Status of Alternative Anti-Inflammatory Therapies in the Treatment of Asthma: Critical Appraisal , 1994 .

[15]  G. Cott.  Perspectives on methotrexate in the treatment of asthma. , 1994, Chest.

[16]  D. Faulds,et al.  Methotrexate: A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Rheumatoid Arthritis and Other Immunoregulatory Disorders , 1994 .

[17]  G. Toews,et al.  The role of methotrexate in the management of steroid-dependent asthma. , 1994, Chest.

[18]  E. Flannery,et al.  Methotrexate in the management of severe steroid dependent asthma. , 1993, The New Zealand medical journal.

[19]  R. Davies,et al.  Comparison of methotrexate 30 mg per week with placebo in chronic steroid-dependent asthma: a 12-week double-blind, cross-over study. , 1993, Respiratory medicine.

[20]  B. Delclaux,et al.  Methotrexate and asthma. , 1993, Chest.

[21]  D. Taylor,et al.  Steroid–sparing agents in the treatment of asthma , 1992, The Medical journal of Australia.

[22]  S. Szefler,et al.  Anti-inflammatory drugs in the treatment of allergic disease. , 1992, The Medical clinics of North America.

[23]  R. Weber,et al.  Methotrexate in the treatment of steroid-dependent asthma. , 1991, The Journal of allergy and clinical immunology.

[24]  Methotrexate in bronchial asthma. , 1991, The Journal of allergy and clinical immunology.

[25]  S. Erzurum,et al.  Effect of low-dose methotrexate on the disposition of glucocorticoids and theophylline. , 1991, The Journal of allergy and clinical immunology.

[26]  M. Mullarkey.  Methotrexate and asthma. , 1991, The Journal of allergy and clinical immunology.

[27]  R. Farr,et al.  Abnormal liver-function tests associated with long-term systemic corticosteroid use in subjects with asthma. , 1991, Journal of Allergy and Clinical Immunology.

[28]  W. Klaustermeyer,et al.  Variability of pulmonary function tests in stable corticosteroid dependent asthma patients. , 1991, Allergy proceedings : the official journal of regional and state allergy societies.

[29]  L. Ackerson,et al.  Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double-blind, placebo-controlled study. , 1991, Annals of internal medicine.

[30]  W. Busse,et al.  633 Use of oral methotrexate (MTX) in corticosteroid (CS)-dependent adult asthma: A twenty-four month analysis , 1991 .

[31]  A. Wanner,et al.  Methotrexate: does it treat or induce asthma? , 1991, The American review of respiratory disease.

[32]  E. Mierins,et al.  Methotrexate-induced asthma. , 1991, The American review of respiratory disease.

[33]  K. Chung,et al.  Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma , 1990, The Lancet.

[34]  G. A. Bailey,et al.  Methotrexate in the treatment of corticosteroid-dependent asthma. A double-blind crossover study. , 1988, The New England journal of medicine.

[35]  K. Kragballe,et al.  Methotrexate inhibits the human C5a-induced skin response in patients with psoriasis. , 1987, The Journal of investigative dermatology.

[36]  P. Kerkhof,et al.  Reduction of leukotriene B4‐induced intraepidermal accumulation of polymorphonuclear leukocytes by methotrexate in psoriasis , 1987, The British journal of dermatology.

[37]  S. Kerwar,et al.  Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and complement C5a. , 1987, The Journal of rheumatology.

[38]  Mullarkey Mf,et al.  Methotrexate in the treatment of steroid-dependent asthma. , 1986 .

[39]  D. Webb,et al.  Methotrexate in the treatment of steroid-dependent asthma. , 1986, Annals of allergy.