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DOP084. An accelerated infliximab dosing strategy for rescue therapy in acute severe colitis is associated with reduced early colectomy rate

D.J. Gibson, Z. Heetun, K. Byrne, D. Keegan, G. Cullen, H. Mulcahy, G.A. Doherty, St. Vincent's University Hospital, Centre for Colorectal Disease, Dublin, Ireland

Background

Rescue infliximab (IFX) in Acute Severe UC reduces rates of early colectomy, but long-term colectomy rates are similar to the pre-biologic era. Preliminary data suggests that the infliximab half life is considerably shorter in acute severe colitis. We hypothesised that patients require higher doses of IFX than standard induction dosing in Acute Severe UC to achieve therapeutic levels. By delivering IFX at shorter intervals during induction, higher trough levels could be achieved, and patients could be successfully treated medically without the need for colectomy.

Methods

Retrospective analysis of a prospectively maintained database of patients with IBD (n = 3,200). Patients who required hospitalisation and were given rescue infliximab for acute severe colitis from June 2005-September 2013 at a single academic centre were identified. In 2011 an accelerated dosing protocol for IFX was introduced. Patients given standard dosing (SD) received infliximab at time 0, 2, and 6 weeks and 8 weekly thereafter. Patients given accelerated dosing (AD) received all three induction doses of IFX within 2 weeks and 8 weekly thereafter. Rates of colectomy were compared between the 2 groups at 3, 6 and 12 months.

Results

52 patients received infliximab; 38 received SD and 14 received AD. There were no differences in median CRP (SD = 54, AD = 38 p = 0.4), median albumin (SD = 23, AD = 22.5, p = 0.64), median platelet count (SD = 390, AD = 414, p = 0.84), median haemoglobin (11.0 SD, 10.5 AD p = 0.76) or median disease duration (SD = 11.8 years, AD = 5.3 years, p = 0.47) between the 2 groups on the day of induction.

18/38 (47.3%) required surgery in the standard regimen and 4/14 (28.5%) in the accelerated regimen during follow-up. Rate of colectomy at 3 months was significantly lower with AD versus SD; 1/14 (7.1%) vs 14/38 (36.8%), fisher exact test p = 0.04. A trend toward reduced colectomy rate remained at 6 months; 2/14 (14.3%) versus 14/38 (36.8%), p = 0.18. At 12 months colectomy rates were more comparable; 4/14 (29%) versus 15/38 (39%), p = 0.53.

Table: Patient demographics
Standard dosing (SD)Accelerated dosing (AD)P value
Male gender (%)55500.76
Median length of disease (months) prior to IFX (IQR)11.8 (0.9–70.5)5.3 (1.0–45.0)0.47
Median age (years) at induction (IQR)35.9 (28.6–44)38.4 (31.2–55.3)0.24
Median haemoglobin (g/dL) at induction (IQR)11.0 (10.0–12.0)10.8 (9.5–11.8)0.76
Median platelet count (109/L) at induction (IQR)390 (330–463)414 (311–463)0.84
Median albumin (g/L) at induction (IQR)23 (21–30)22.5 (22–25)0.64
Median CRP (mg/L) at induction (IQR)38 (19.4–71.3)54.1 (26.1–70.5)0.40

Conclusion

Use of an accelerated induction regimen with IFX is protective against early colectomy in acute severe colitis. These findings suggest that higher IFX doses may be required in severe colitis due to high levels of TNF alpha and more rapid drug clearance. A more aggressive dosing strategy, guided by measurement of IFX levels, may assist in maintaining early success in avoiding colectomy.