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

Abstract

Summary 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 108 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.

Effectiveness and safety of methotrexate monotherapy in patients with Crohn’s disease refractory to anti‐TNF‐α: results from the ENEIDA registry

“…Safety is always an important concern. Rates of methotrexate‐related adverse events described as well as of its discontinuation are similar to previous reports 40,41 . Gabbani et al reviewed the overall safety of methotrexate in patients with inflammatory bowel disease 42 .…”

Dietary Management in Pediatric Patients with Crohn’s Disease

“…Moreover, inflammation itself (i.e., via TNF-α and IL-6) can cause a reduction in appetite via catabolic effects and hypothalamic weight regulation [ 39 ]. In addition, some of the most commonly prescribed medications can induce nausea, vomiting and/or anorexia [ 40 ]. Lastly, some patients and/or their parents believe that certain foods may worsen, or even elicit, their symptoms.…”

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India

“…Thiopurine drugs are commonly used in inflammatory bowel disease (IBD) for maintenance of remission because of their immunomodulatory and steroid sparing effects [ 1 , 2 ]. The availability of long-term data on the safety, efficacy and cost-effectiveness (especially in relation to biologics) make them an attractive option for use by clinicians [ 2 , 3 ]. The indication for use of thiopurines in IBD include maintenance of remission in Crohn's disease (CD) and for patients with steroid dependent and refractory ulcerative colitis (UC).…”