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Thiopurines less tolerable in women over 40 with Crohn's disease
Adverse events leading to cessation of thiopurine treatment was more common in women over the age of 40 vs. other patients with Crohn’s disease, according to recent findings published in the World Journal of Gastroenterology.
“Thiopurines are commonly used as first line immunosuppressive therapy in subjects with moderate-severe [Crohn’s disease] but adverse events are a common occurrence leading to discontinuation of therapy in one in three patients,” Gordon W. Moran, MD, PhD, from the biomedical research unit at Nottingham Digestive Diseases Centre, University of Nottingham, told Healio Gastroenterology.
Gordon W. Moran
The incidence of adverse events was observed in a retrospective chart review that Moran and colleagues conducted between August 2010 and June 2012. The cohort included 351 patients with Crohn’s disease that researchers identified through the Alberta IBD Consortium patient database registry.
After a median follow-up of 5.8 years, 31.3% (n = 110) of patients discontinued thiopurine therapy. Among them, 7.1% (n = 25) withdrew from treatment because of hypersensitivity reactions, 6.2% (n = 22) from acute pancreatitis, 5.4% (n = 19) from GI intolerance, 3.7% (n = 13) from leucopenia, 3.4% (n = 12) from hepatotoxicity, 1.1% (n = 4) from infection (two cases of intra-abdominal abscesses, one case of molluscum contagiosum and one case of pulmonary coccidioidomycosis) and 4.3% (n = 15) from other adverse events.
The median time from onset of adverse event to treatment withdraw was:
- 31 days (interquartile range [IQR], 29-65) for hypersensitivity reactions;
- 29 days (IQR, 14.5-30) for acute pancreatitis;
- 17 days (IQR, 7-26) for GI toxicities; and conversely,
- 347.5 days (IQR, 159-866) for leucopenia.
An analysis adjusted for age and gender demonstrated that patients over 40 years at the time thiopurine therapy was initiated were more likely to discontinue use compared with patients under the age of 40 (P = .007). Furthermore, women over 40 were four times more likely to discontinue treatment vs. women under 40 (OR = 4; 95% CI, 1.9-8.3).
The researchers observed a sex-by-age interaction (P = .04) which showed that women older than 40 years had a higher risk of discontinuing therapy due to an adverse event vs. women younger than 40 years (OR = 2.8; 95% CI, 1.4-5.6). However, age was not a predictor of discontinuation among men (OR = 0.9; 95% CI, 0.4-2.1).
“This study demonstrates real-life clinical practice that suggests that combination strategies with anti-TNF therapy and long-term thiopurine monotherapy are therapeutic aims that might not be easy to achieve for patients with [Crohn’s disease],” Moran said. “In this patient cohort who is not usually of child-bearing age, methotrexate therapy might be a strategy worth pursuing.”
Further analysis considering other variables, including the location of the disease and phenotype, perianal disease, smoking status, intestinal resection history and prior 5-ASA or corticosteroid use, were not significantly associated with adverse events and withdraw, according to the researchers. They concluded that future research validating their findings is warranted. – by Stephanie Viguers
Disclosure: Moran reports receiving fees as a consultant from AbbVie and receiving financial support from AbbVie, MSD, Merck Sharp and Dohme Ltd and Ferring. Please see the full study for a list of all other authors’ relevant financial disclosures.