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P588 Tacrolimus suppositories: a safe and effective treatment for treatment-refractory proctitis

R. Smith*1, H. Weekes2, L. Morgan2, M. Parkes1, J. C. Lee1

1University of Cambridge, Department of Medicine, Cambridge, UK, 2Addenbrooke's Hospital, Pharmacy, Cambridge, UK

Background

Treatment-refractory proctitis is a miserable condition, with intractable urgency, tenesmus and often very high stool frequency and bleeding. These symptoms are both disabling and often highly distressing for patients, and yet because this patient group has been excluded from most biologic trials, the optimal treatment approach is unclear. Indeed, even surgery—the standard treatment for medically refractory UC—will initially leave most of the active disease behind. As such these patients can be extremely difficult to manage. Several small studies have suggested that topical tacrolimus can be an effective treatment in this cohort of patients. Here, we report our initial experience in a real-world setting.

Methods

Tacrolimus suppositories (2 mg) were made-to-order by a ‘specials’ pharmaceutical company (Martindale). Eligible patients with endoscopically-confirmed treatment-refractory proctitis (moderate–severely active) were identified from an outpatient setting and treatment (rectal tacrolimus 2 mg b.d. for 4 weeks) was initiated by gastroenterologists with an interest in IBD. Serum tacrolimus levels were checked once. Treatment response was assessed using a combination of PRO2 (rectal bleeding and stool frequency components of the Mayo score) and physician’s global assessment.

Results

Between 2015 and 2018, 21 patients were treated with a total of 35 courses of topical tacrolimus. Twenty had UC and 1 had Crohn’s disease. These patients had highly refractory disease (Figure 1), and 17 (81%) had required hospital admission and/or systemic steroids within the preceding year. The average number of immunomodulators and/or biologics previously used was 1.5 per patient. After 4 weeks of topical tacrolimus, 13 patients (62%) achieved clinical remission (PRO2 = 0), and a further 3 (14%) showed a clinical response (PRO2 decrease by >2 points) (Figure 2). Five patients (24%) did not respond. Serum tacrolimus levels were generally low (median 5.7 ng/ml) but did significantly correlate with clinical response (p = 0.002). In responders the average time to the next relapse was 9 months, and re-treatment with tacrolimus suppositories was clinically effective in 87% of cases. No side-effects were reported.

Figure 1. Previous treatments used.

Figure 2. PRO2 scores before and after treatment.

Conclusion

Tacrolimus suppositories are a safe and effective treatment for most patients with treatment-refractory proctitis.