P423 Azathioprine still remains the first step-up therapy in patients with Inflammatory Bowel Disease in low-middle income countries.
Ranjan, M.K.(1);Kumar, P.(1);Vuyyuru, S.K.(1);Kante, B.(1);Sahu, P.(1);Mundhra, S.(1);Golla, R.(1);Singh, M.(1);Virmani, S.(1);Sharma, R.(1);Panwar, R.(1);Das, P.(1);Makharia, G.(1);Kedia, S.(1);Ahuja, V.(1);
(1)All India Institute of Medical Sciences, Department of Gastroenterology and Human Nutrition, New Delhi, India;
Background
Inflammatory bowel disease (IBD) including Ulcerative Colitis (UC) and Crohn’s Disease (CD) is characterized by remitting/relapsing course. A proportion of patients with UC, and almost all patients with CD require long-term immunosuppression to maintain endoscopic and clinical remission and prevent disease progression. The present study aimed to evaluate the long-term efficacy of thiopurines, their predictors, and the effect of the early use of thiopurines on disease outcomes in patients with IBD.
Methods
A retrospective cohort analysis of patients with IBD following up in IBD clinic at AIIMS, New Delhi, India from 2004-2020. Efficacy was defined as a state of not requiring hospitalization, anti-TNF agents, surgery, and only minimum (≤ 1 steroid course in 2 years) steroid requirement during follow-up. Early and late thiopurine initiation was defined as commencement of thiopurines ≤2 and >2 years of disease onset, respectively.
Results
Of 1264 consecutive patients on thiopurines (both 6-MP and azathioprine), 988 (UC:720, CD:268) were considered for efficacy analysis (males-60.8%, mean age at disease onset-31.69±12.34 years and thiopurine initiation-35±13.14 years). Time to event analysis showed a median efficacy rate of 79%, 72% and 68%, 61% at 5 and 10 years in UC and CD patients respectively after thiopurine initiation. On multivariate analysis, only the male sex was found to be a significant predictor of relapse (HR: 1.49, 95% CI: 1.021-2.194; P=0.039) in UC and Ileal involvement (HR: 0.391, 95% CI: 0.176-0.86; P= 0.021) and steroid-dependent disease (HR: 0.429, 95% CI: 0.186-0.965; P= 0.041) were associated with decreased risk of relapse and presence of any adverse event was associated with increased risk of relapse (HR: 2.37, 95%CI: 1.39-4.05; P=0.008). Kaplan Meier survival analysis showed no difference between the efficacy of early and late thiopurine groups, both in UC (Log-rank test P = 0.72) and CD (Log-rank test P = 0.76).
Figure 1: Kaplan Meier curve showing relapse-free survival on thiopurine in ulcerative colitis and Crohn’s disease. 
Figure 2: Kaplan Meier survival analysis comparing relapse-free survival in early vs late thiopurine initiation group in UC (Log-rank test P = 0.72).
Figure 3: Kaplan Meier survival analysis comparing relapse-free survival in early vs late thiopurine initiation group in CD (Log-rank test P-value: 0.764).
Conclusion
Thiopurines still remains a viable long-term option for maintenance of remission in patients with IBD, especially in resource-limited countries. Their use can be further enhanced by optimizing their therapy and regular monitoring for adverse events.