Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease
Por:
Rodriguez-Lago, I, Castro-Poceiro, J, Fernandez-Clotet, A, Mesonero, F, Lopez-Sanroman, A, Lopez-Garcia, A, Marquez, L, Clos-Parals, A, Canete, F, Vicuna, M, Nantes, O, Merino, O, Matallana, V, Gordillo, J, Elorza, A, Vicente, R, Casanova, MJ, Ferreiro-Iglesias, R, Perez-Galindo, P, Benitez, JM, Taxonera, C, Garcia, MJ, Martin, E, Aguirre, U, Gisbert, JP
Publicada:
1 may 2020
Ahead of Print:
1 mar 2020
Resumen:
Background Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD).
Aims To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice.
Methods We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment.
Results One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs <10 ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3 months. Of 62 patients with perianal disease, complete closure was observed in 8% (n = 5) of patients with perianal fistulas, with 34% (n = 21) showing partial response. Treatment was maintained for a median of 6 months (IQR, 2-16). After a median clinical follow-up of 24 months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P = 0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC.
Conclusions Tacrolimus shows a clinical benefit in both CD and UC after 3 months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.
Filiaciones:
Rodriguez-Lago, I:
Hosp Galdakao Usansolo, Galdakao, Spain
Biocruces Bizkaia Hlth Res Inst, Baracaldo, Bizkaia, Spain
Castro-Poceiro, J:
Hosp Clin Barcelona, Barcelona, Spain
Fernandez-Clotet, A:
Hosp Clin Barcelona, Barcelona, Spain
Mesonero, F:
Hosp Univ Ramon y Cajal, Madrid, Spain
Lopez-Sanroman, A:
Hosp Univ Ramon y Cajal, Madrid, Spain
Lopez-Garcia, A:
Hosp del Mar, Barcelona, Spain
Hosp del Mar, Med Res Inst IMIM, Barcelona, Spain
Marquez, L:
Hosp del Mar, Barcelona, Spain
Hosp del Mar, Med Res Inst IMIM, Barcelona, Spain
Clos-Parals, A:
Hosp Badalona Germans Trias & Pujol, Barcelona, Spain
Canete, F:
Hosp Badalona Germans Trias & Pujol, Barcelona, Spain
Vicuna, M:
Complejo Hosp Navarra, Pamplona, Spain
Nantes, O:
Complejo Hosp Navarra, Pamplona, Spain
Merino, O:
Hosp Univ Cruces, Baracaldo, Bizkaia, Spain
Matallana, V:
Hosp Univ Puerta Hierro, Madrid, Spain
Gordillo, J:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Elorza, A:
Hosp Galdakao Usansolo, Galdakao, Spain
Vicente, R:
Hosp Univ Miguel Servet, Zaragoza, Spain
Casanova, MJ:
Hosp Univ Princesa, Inst Invest Sanitaria Princesa IISIP, Madrid, Spain
CIBEREHD, Madrid, Spain
Ferreiro-Iglesias, R:
Hosp Clin Univ Santiago de Compostela, Santiago De Compostela, Spain
Perez-Galindo, P:
Hosp Montecelo, Pontevedra, Spain
Benitez, JM:
Hosp Univ Reina Sofia, Cordoba, Spain
IMIBIC, Cordoba, Spain
Taxonera, C:
Hosp Clin San Carlos, Madrid, Spain
Garcia, MJ:
Hosp Univ Marques de Valdecilla, Santander, Spain
Martin, E:
Hosp Univ La Paz, Madrid, Spain
Aguirre, U:
Hosp Galdakao, Red Invest Serv Salud Enfermedades Cron REDISSEC, Galdakao, Spain
Gisbert, JP:
Hosp Univ Princesa, Inst Invest Sanitaria Princesa IISIP, Madrid, Spain
CIBEREHD, Madrid, Spain
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