Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year

Abstract

Summary Introduction : Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated. Aims : To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose–response relationship. Patients and methods : In an open 12‐month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise ≥ 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention. Results : Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017). Conclusions : Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.

Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

“…All 4 RCTs in CD reported higher relapse rates after stopping the immunomodulator compared with continuing the drug. [8][9][10][11] All RCTs focused on azathioprine exclusively and the longest follow-up was for 2 years after withdrawal. 10 The study by Lemann et al was designed as a noninferiority study, and the investigators concluded that they could not reject the hypothesis that placebo was inferior to continuing azathioprine.…”

“…These comprised 5 RCTs 8-12 and 13 retrospective cohort studies [13][14][15][16][17][18][19][20][21][22][23][24][25] (one of which 20 was an extension study from a previous RCT 8 ). Eleven studies reported on immunomodulator withdrawal in CD [8][9][10][11]14,15,17,20,[23][24][25] and 8 in UC. 12,13,[17][18][19]21,22,24 One study by Fraser et al reported on long-term outcomes of patients treated with methotrexate and presented relapse rates for IBD with no distinction between CD and UC.…”

Fulminant ulcerative colitis associated with steroid-resistant minimal change disease and psoriasis: A case report

“…Abrupt withdrawal of immunosuppressive treatment might contribute to his fulminant presentation of ulcerative colitis. Previous studies also demonstrated that withdrawal of azathioprine could lead to a relapse of IBD activity [21,22] .…”

Bovine lactoferrin and Crohn’s disease: a case study

“…7 15 NS NR 8 of 15 (Vilien, et al, 2004) (Gross, et al, 1998) 13 1 NS Less than 1 year 0 of 1 (Lennard-Jones, 1977) 14a 11 C 3 months to 2 years 6 of 11 (Prantera, et al, 1992) 14b 18 IC 3 months to 2 years 9 of 18 (Prantera, et al, 1992) 14c 32 I 3 months to 2 years 17 of 32 (Prantera, et al, 1992) (Gendre, et al, 1993) 21b #48 NS 3 months to 2 years 22% 42% (Gendre, et al, 1993) 22 101, 57 NS 1 -2 years or less 36 of 101 34 of 57 (Summers, et al, 1979) 23a 7 C 12 months or more 0 of 7 (Wenzl, et al, 2015) 23b 14 IC 12 months or more 7 of 14 (Wenzl, et al, 2015) 23c 5 I 12 months or more 1 of 5 (Wenzl, et al, 2015) 24 § § § § ~ 65% (Malchow, et al, 1984) 25 #10 NS NR 50% (Nyman, et al, 1985) (Steenholdt, et al, 2012) 9 100 95 4% 7% 12% 20% 27% 48% NR (Papamichael, et al, 2015) …”