Thiopurines vs methotrexate: Comparing tolerability and discontinuation rates in the treatment of inflammatory bowel disease.

Autor: Vasudevan A; Department of Gastroenterology and Hepatology, Monash University, Eastern Health Clinical School, Victoria, Australia., Parthasarathy N; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Con D; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Nicolaides S; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Apostolov R; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Chauhan A; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Bishara M; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Luber RP; Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia., Joshi N; Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia., Wan A; Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia., Rickard JA; Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Australia., Long T; Monash University, Eastern Health Clinical School, Victoria, Australia., Connoley D; Monash University, Eastern Health Clinical School, Victoria, Australia., Sparrow MP; Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia., Gibson PR; Department of Gastroenterology, Alfred Health and Monash University, Victoria, Australia., van Langenberg DR; Department of Gastroenterology and Hepatology, Monash University, Eastern Health Clinical School, Victoria, Australia.
Jazyk: angličtina
Zdroj: Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2020 Oct; Vol. 52 (7), pp. 1174-1184. Date of Electronic Publication: 2020 Aug 14.
DOI: 10.1111/apt.16039
Abstrakt: Background: There are safety concerns regarding immunomodulators (thiopurines and methotrexate) for treatment of inflammatory bowel disease (IBD).
Aim: To compare the long-term tolerability, and persistence of thiopurine and methotrexate therapy in IBD.
Methods: A retrospective cohort study was performed at two hospitals between 1 January 2004 and 31 December 2016 for patients commenced on thiopurines or methotrexate for IBD. Treatment discontinuation rates, intolerances and disease activity were obtained from medical records.
Results: There were 782 patients commenced on immunomodulator therapy; 244 (31%) on methotrexate with folate (67% subcutaneous therapy) and 538 (69%) on thiopurine (73% azathioprine). Median follow-up was 42 vs 47 months (P = 0.09). In patients on thiopurines, median 6-TGN was 298 pmol/8 x 10 8 RBCs, while the median dose of methotrexate was 25 mg weekly. Methotrexate recipients had a higher rate of prior immunomodulator intolerance, were typically older and had a longer disease duration (54% vs 3%, median 43 vs 36 years, 6 vs 5 years, respectively, each P < 0.05). Overall, 208 (27%) discontinued therapy due to adverse events, (40% on methotrexate vs 19% on thiopurines, P < 0.001), including nausea (18% vs 4%), fatigue (7% vs 2%) and hepatotoxicity (8% vs 2%, each P < 0.001). Hospitalisations from adverse events (0.8% vs 0.9%) and serious infections (9% vs 12%), and deaths (1% vs 0%) were comparable between groups (all P > 0.05). Discontinuation due to adverse events occurred later in patients on methotrexate than on thiopurines (median 7 vs 5 months, P = 0.08).
Conclusion: Discontinuation of methotrexate occurred at rates twice that of dose-optimised thiopurine therapy.
(© 2020 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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