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P383. Response rates and side effects after 26 weeks of tacrolimus, infliximab or cyclosporine in patients with steroid refractory ulcerative colitis – Swiss IBD cohort study

M. Protic1, P. Frei2, Z. Radojicic3, A. Schoepfer4, P. Juillerat5, C. Mottet6, G. Rogler7, C. Beglinger8, F. Seibold1, 1Spital Netz Bern, Gastroenterology, Bern, Switzerland, 2See Spital, Gastroenterology, Horgen, Switzerland, 3Faculty of Organizational Sciences, Statistcs, Belgrade, Serbia, 4Centre hospitalier universitaire Vaudois, Gastroenterology, Lausanne, Switzerland, 5University Hospital Bern Inselspital, Gastroenterology, Bern, Switzerland, 6Hospital Neuchâtel, Gastroenterology, Neuchâtel, Switzerland, 7University Hospital Zürich, Gastroenterology, Zürich, Switzerland, 8University Hospital Basel, Gastroenterology, Basel, Switzerland

Background

Cyclosporine (CsA), Tacrolimus (Tcl) and Infliximab (IFX) are effective rescue therapies in steroid-refractory ulcerative colitis (UC). Their use has been limited by safety concerns.

Methods

Response to treatment and adverse event (AE) profiles of patients with steroid-refractory moderate to severe UC was retrospectively studied in three cohorts: Cohort A (n = 32) treated with oral Tcl (initially 0.05 mg/kg twice daily, aiming for serum trough levels of 7–12 ng/mL); Cohort B (n = 28) treated with intravenous CsA 2 mg/kg/daily and then oral CsA 5 mg/kg/daily; Cohort C (n = 63) treated with IFX (5 mg/kg intravenously at week 0, 2, 6 and then every 8 weeks). After successful rescue therapy with Tcl or CsA, thiopurine maintenance therapy or maintenance with Tcl (in Tcl pre-treated patients) was introduced. The endpoints were evaluation of short and medium term response (on the basis of modified Truelove–Witts severity index [MTWSI]) and AE rates for three drugs.

Results

Clinical response (decrease of MTWSI score of more than 4 points) at week 6 was achieved by 71% (23/32) of patients on Tcl, compared to 60% (17/28) on CsA and 79% (50/63) on IFX (P = 0.176). After 26 weeks, response rates decreased to 56% (18/32) in Tcl group, 35.7% (10/28) on CsA and 71.5% (45/63) given IFX (P = 0.005). Subgroup analysis showed the lowest medium term response rate in CsA group among moderate patients: 53.7% (11/13) on Tcl, 25% (1/4) on CsA and 80% (24/30) on IFX (P = 0.037). AEs in first 6 weeks were observed in 9.3% (3/32) of patients on Tcl, 21.4% (6/28) on CsA and 9.5% (6/63) on IFX (P = 0.236). After 6 months, side effects were identified in 15% (4/27) on Tcl, 28% (5/18) on CsA and 15% (9/60) on IFX; (P = 0.421).

Table: Overview of Adverse Events
Rescue therapyAE week 6AE week 26
TclTremor, Hair loss, Otitis mediaTremor, Hair loss, Elevation of AST, ALT, Anemia
CsATremor (3 pts), Neuropathy, Headache, Hands paresthesiaMild transitional renal insufficiency (3 pts), Tremor (4 pts), Neuropathy, Arterial hypertension
IFXSevere allergic reaction (3 pts)*, Foot and hand erythema, Herpes simplex infection, Hair lossSevere allergic reaction (3 pts)*, Lupus-like syndrome*, Alopecia, Skin abscess, Atopic dermatitis, Respiratory infection, Post infusion diarrhea
*Resulted with IFX discontinuation.

Conclusion

After similar short term response to three rescue treatments, medium term response rate was significantly lower in CsA group compared to IFX and Tcl, especially among moderate patients. Safety profiles were comparable in all 3 rescue treatments groups. The most severe AE observed in the study cohorts were severe allergic reactions to IFX. Tcl and CsA were well tolerated: mild transitional renal insufficiency was successfully managed by decreasing CsA dose.