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* = Presenting author

P587 Tacrolimus suppositories in therapy-resistant ulcerative proctitis - a single center experience

S. Jaeger*1, K. Hoeger1, J. Wehkamp2, E. Stange1, M. Escher1

1Robert Bosch Krankenhaus, Gastroenterology, Stuttgart, Germany, 2University of Tuebingen, Gastroenterology, Tuebingen, Germany

Background

Ulcerative proctitis may be often managed with topical salicylates or budesonide alone, but in some patients, symptoms can be persistent, severe and have a profound impact on quality of life. Here we present an analysis from our outpatient clinic with add-on therapy of tacrolimus suppositories in patients who remained symptomatic despite conventional systemic and topical therapy.

Methods

We followed up 25 patients with ulcerative proctitis (E1, Montreal classification). Patients already received oral therapy consisting of an immunomodulator, prednisolone, salicylates and topical treatment with steroids or saliclyates. CAI according to Rachmilewitz was assessed at start of tacrolimus treatment and at every follow-up visit. The content of one 2 mg capsule of tacrolimus was moulded into suppositories by our pharamceutical department. Patients took 1 suppository BID. Tacrolimus serum levels, CRP, complete blood count and ESR along with creatinine were assessed via routine laboratory. Data was analyzed with Graph Pad Prisms.

Results

Median time from baseline to a consultation with assessment of CAI and tacrolimus serum level was 75 days. Three patients discontinued treatment after they experienced worsening of symptoms. Including these treatment failures, patients showed a significant decrease in CAI from 7,8 to 5,7 points (p=0,0279).

Mean tacrolimus trough level (n = 17) was 5,25 ng/mL (SD +/-2,601). The mean time from application of the last suppository was 17,6 hours (SD +/-6,862). The highest individual level was 10,2 ng/mL. We furthermore found a significant, moderate correlation between the change in CAI from baseline to follow-up and the height of tacrolimus trough level (Spearman r -0,555 (95% CI -0,8291 to - 0,0657; p = 0,025). In terms of side effects, we registerd 1 case of hypertension, 2 cases of tingling sensation in hands and feet and tremor, 1 case of headache, muscle cramps at night and unspecific fatigue.

Conclusion

After addition of a topical formulation of tacrolimus (suppositories) in ulcerative proctitis refractory to standard treatment, we observed a significant decrease in CAI scores over a median treatment duration of 75 days. Mean tacrolimus serum levels were 5,253 ng/mL, and clinical benefit positively correlated with the height of serum levels. As envisioned by the use of topical treatment, side effects were rare and mild. On the other hand, tacrolimus serum levels were high enough to suggest that clinical benefit might be due to systemic tacrolimus effects. In this retrospective, observational study form our outpatient clinic, tacrolimus suppositories were used with success. Nevertheless, a further prospective study is needed to confirm these findings.