Methotrexate versus azathioprine in patients with atopic dermatitis: 2-year follow-up data

• Published in: Journal of allergy and clinical immunology Vol. 141; no. 2; pp. 825 - 827.e10
• Main Authors: Roekevisch, Evelien, Schram, Mandy Elvira, Leeflang, Mariska Maria Geertruida, Brouwer, Marijke Willemijn Dorothée, Gerbens, Louise Anna Andrea, Bos, Jan Dositheus, Spuls, Phyllis Ira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2018; Elsevier Limited
• Subjects: Atopic dermatitis; Azathioprine; Chronic illnesses; Clinical trials; Dermatitis; Eczema; Enzymes; Immunosuppression; Infections; Methotrexate; Mutation; Neoplasia; Patients; Poisoning; United States > US
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2017.09.033

[...]for other outcome measures, there was no significant difference between treatments, except for the Patient Global Assessment in the PP analysis, which showed a favorable effect for the AZA group. Because the Patient Global Assessment gives insight into the patient's own health experience, this may be an important finding. [...]because AD is a chronic disease, it is imperative that any proposed therapy has persistent efficacy and acceptable side effects during years of use. Variable Total AEs (n = 35) Total AEs/pt (n = 35) Total AEs MTX group (n = 17) Total AEs MTX group/pt (n = 17) Total AEs AZA group (n = 18) Total AEs AZA group/pt (n = 18) P value AEs, total events, no. of pt∗ 422 1.06 220 12.94 202 11.22 .14 Mild, no. of pt 372 10.63 198 11.65 174 9.67 .07 Moderate, no. of pt 45 1.29 21 1.24 24 1.33 .80 Severe, no. of pt 5 0.14 1 0.06 4 0.22 .20 SAEs, total events, no. of pt∗ 3 0.09 2 0.12 1 0.06 .53 Treatment-related AEs, no. of pt† 252 7.20 133 7.82 119 6.61 .18 AEs requiring dose adjustment, no. of pt 6 0.17 4 0.24 2 0.11 .38 Type of AE coded according to MedDRA, no. of pt Blood and lymphatic system disorders 34 0.97 11 0.65 23 1.28 .058 Cardiac disorders 9 0.26 4 0.24 5 0.28 .80 Eye disorders 7 0.20 5 0.29 2 0.11 .23 Gastrointestinal disorders 44 1.26 26 1.53 18 1.00 .16 General disorders and administration site conditions 46 1.31 22 1.29 24 1.33 .92 Hepatobiliary disorders 20 0.57 11 0.65 9 0.50 .57 Immune system disorders 1 0.03 0 0.00 1 0.06 .33 Infections and infestations 98 2.80 52 3.06 46 2.56 .37 Ear and labyrinth disorders 2 0.06 1 0.06 1 0.06 .97 Eye disorders 2 0.06 2 0.12 0 0.00 .15 General disorders and administration site conditions 11 0.31 2 0.12 9 0.50 .04 Musculoskeletal and connective tissue disorders 9 0.26 3 0.18 6 0.33 .36 Neoplasms benign, malignant, and unspecified‡ 4 0.11 4 0.24 0 0.00 .04 Renal and urinary disorders 5 0.14 4 0.24 1 0.06 .16 Reproductive system and breast disorders 1 0.03 0 0.00 1 0.06 .33 Respiratory, thoracic, and mediastinal disorders 27 0.77 15 0.88 12 0.67 .46 Skin and subcutaneous tissue disorders 37 1.06 21 1.24 16 0.89 .31 Bacterial 19 0.54 11 0.65 8 0.44 .41 Viral 10 0.29 5 0.29 5 0.28 .93 Fungal 6 0.17 3 0.18 3 0.17 .94 Injury, poisoning, and procedural complications 8 0.23 4 0.24 4 0.22 .94 Metabolism and nutrition disorders 1 0.03 0 0.00 1 0.06 .33 Musculoskeletal and connective tissue disorders 28 0.80 16 0.94 12 0.67 .36 Neoplasms benign, malignant, and unspecified‡ 9 0.26 3 0.18 6 0.33 .36 Nervous system disorders 34 0.97 20 1.18 14 0.78 .23 Psychiatric disorders 2 0.06 0 0.00 2 0.11 .17 Renal and urinary disorders 11 0.31 6 0.35 5 0.28 .69 Reproductive system and breast disorders 4 0.11 2 0.12 2 0.11 .95 Respiratory, thoracic, and mediastinal disorders 16 0.46 10 0.59 6 0.33 .27 Skin and subcutaneous tissue disorders 47 1.34 26 1.53 21 1.17 .36 Surgical and medical procedures 3 0.09 2 0.12 1 0.06 .53 Type of SAE coded according to MedDRA, no. of pt Injury, poisoning, and procedural complications 1 0.03 1 0.06 0 0.00 .30 Skin and subcutaneous tissue disorders 2 0.06 1 0.06 1 0.06 .97 Table E5 AEs and other key safety data up to 2 years after baseline in patients who were continuously on allocated treatment (PP analysis) Significant values are in boldface.MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; pt, patient. Variable Total AEs (n = 18) Total AEs/pt (n = 18) Total AEs MTX group (n = 10) Total AEs MTX group/pt (n = 10) Total AEs AZA group (n = 8) Total AEs AZA group/pt (n = 8) P value MTX vs AZA Total AEs, no. of pt∗ 203 11.3 122 12.2 81 10.1 .19 Mild, no. of pt 183 10.2 107 10.7 76 9.5 .43 Moderate, no. of pt 18 1 15 1.5 3 0.4 .02 Severe, no. of pt 2 0.1 0 0 2 0.3 .11 Total serious AEs, no. of pt∗ 2 0.1 1 0.1 1 0.1 .87 Treatment-related AEs, no. of pt† 131 7.3 76 7.6 55 6.9 .57 AEs requiring dose adjustment, no. of pt 4 0.2 3 0.3 1 0.1 .43 Type of AE coded according to MedDRA, no. of pt Blood and lymphatic system disorders 13 0.7 5 0.5 8 1 .22 Cardiac disorders 4 0.2 1 0.1 3 0.4 .22 Eye disorders 4 0.2 3 0.3 1 0.1 .43 Gastrointestinal disorders 23 1.3 16 1.6 7 0.9 .18 General disorders and administration site conditions 24 1.3 9 0.9 15 1.9 .08 Hepatobiliary disorders 13 0.7 11 1.1 2 0.3 .04 Immune system disorders 1 0.1 0 0 1 0.1 .26 Infections and infestations 44 2.4 29 2.9 15 1.9 .17 Eye disorders 1 0.1 1 0.1 0 0 .37 General disorders and administration site conditions 7 0.4 1 0.1 6 0.8 .03 Musculoskeletal and connective tissue disorders 2 0.1 0 0 2 0.3 .11 Neoplasm benign, malignant, and unspecified‡ 1 0.1 1 0.1 0 0 .37 Renal and urinary disorders 3 0.2 3 0.3 0 0 .12 Reproductive system and breast disorders 1 0.1 0 0 1 0.1 .26 Respiratory, thoracic, and mediastinal disorders 14 0.8 12 1.2 2 0.3 .02 Skin and subcutaneous tissue disorders 15 0.8 11 1.1 4 0.5 .17 Bacterial 11 0.6 7 0.7 4 0.5 .59 Viral 3 0.2 3 0.3 0 0 .12 Injury, poisoning, and procedural complications 5 0.3 4 0.4 1 0.1 .27 Metabolism and nutrition disorders 1 0.1 0 0 1 0.1 .26 Musculoskeletal and connective tissue disorders 12 0.7 7 0.7 5 0.6 .85 Neoplasms benign, malignant, and unspecified‡ 8 0.4 3 0.3 5 0.6 .30 Nervous system disorders 18 1 11 1.1 7 0.9 .64 Renal and urinary disorders 7 0.4 4 0.4 3 0.4 .93 Respiratory, thoracic, and mediastinal disorders 10 0.6 7 0.7 3 0.4 .36 Skin and subcutaneous tissue disorders 14 0.8 10 1 4 0.5 .23 Surgical and medical procedures 2 0.1 2 0.2 0 0 .21 Type of SAE coded according to MedDRA, no. of pt Injury, poisoning, and procedural complications 1 0.06 1 0.1 0 0 .37 Skin and subcutaneous tissue disorders 1 0.06 0 0 1 0.1 .26 1 M.E. Schram, E. Roekevisch, M.M. Leeflang, J.D. Bos, J. Schmitt, P.I. Spuls, A randomized trial of methotrexate versus azathioprine for severe atopic eczema, J Allergy Clin Immunol, Vol. 128, 2011, 353-359 2 National Cancer Institute (U.S.), Common terminology criteria for adverse events (CTCAE), Rev., 2009, U.S. Dept. of Health and Human Services, National Institutes of Health, National Cancer Institute 3 E. Roekevisch, M.M. Leeflang, M.E. Schram, L.E. Campbell, W.H. Irwin McLean, S. Kezic, Atopic dermatitis patients with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment, Br J Dermatol, 2016, Epub ahead of print