Minimal risk of lymphoma and non‐melanoma skin cancer despite long‐term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India

Abstract

Background and Aim Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long‐term efficacy and safety of thiopurines. Methods Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long‐term adverse events and development of malignancy. Results Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis—1.9%, left‐sided colitis—44.9%, & pancolitis—53.1%] & CD = 305 [inflammatory—42.6%, stricturing—46.9%, & fistulizing—10.5%]) were included (60.8%—male patients). Follow up and treatment duration on thiopurine were 7 (4–12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty‐nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu‐like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non‐melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). Conclusion Long‐term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non‐melanoma skin cancer.

Personalized medicine to implementation science: Thiopurines set for the leap

“…The risk of Epstein–Barr virus‐associated hepatosplenic T‐cell lymphoma can be mitigated by avoiding thiopurines in young males negative for Epstein‐Barr virus (EBV) serology at baseline. The risk of malignancy may be dependent on the geography and may not be very common in Asians, as reported in a recent retrospective cohort study from northern India, where no case of lymphoma or NMSC was reported over 4788 person‐years of follow‐up 37 . Hence, thiopurines may be continued if patients tolerate and respond under close monitoring for adverse events, as thiopurine withdrawal is associated with the risk of relapse in 50% patients 38 …”

Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis

“… Forest plot of IBD incidence. IR, Incidence Rate; SE, Standard Error ( 4 , 6 , 9 , 11 , 23 – 27 , 29 – 34 , 36 – 45 , 48 , 50 , 51 , 57 ). …”

Long‐term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real‐world experience

“… 22 However, most recently, a longitudinal cohort analysis from north India, which evaluated 1093 IBD patients on AZA with a median follow‐up of 7 years, reported that not a single patient on AZA developed lymphoma or NMSC. 51 Thus, at present, it may be safe to conclude that the benefits of long‐term immune modulation with AZA significantly outweigh the minor risk of malignancy in patients with IBD.…”