Colon Mucosa Exhibits Loss of Ectopic MUC5AC Expression in Patients with Ulcerative Colitis Treated with Oral Tacrolimus

Abstract

Background. Tacrolimus (FK506) is effective for patients with ulcerative colitis (UC). However, there are few reports on tacrolimus therapy (TT) with respect to the relationship with endoscopic and clinicopathologic findings. Methods. Thirty patients with moderate/severe active UC refractory to or dependent on corticosteroid were treated with oral tacrolimus. The expression of ectopic MUC5AC in the colon was pathologically analyzed before and at 12 weeks after TT, evaluating the Mayo score and steroid-sparing effects. Results. Both mean disease and endoscopic activity index scores were reduced at levels of statistical significance in 26 UC patients receiving more than one month of TT (P < 0.0001). The dose of prednisolone was reduced by a statistically significant amount (P = 0.00022), and 14 of the 26 patients (53.8%) had steroid-free status 12 weeks after TT. The decrease in ectopic MUC5AC expression in the mucous cells of the colon was significantly associated with endoscopic improvement of inflammation in the UC patients with TT (P = 0.043). Loss of ectopic MUC5AC expression was detected in all patients who had complete response. Conclusions. Tacrolimus appears to be effective for the treatment of moderate/severe UC patients. Loss of ectopic MUC5AC expression may be important for pathologic remission in the colon of UC patients.

Previous exposure to biologics and C-reactive protein are associated with the response to tacrolimus in inflammatory bowel disease

“…We can obtain more evidence, almost all from retrospective studies, demonstrating relatively good efficacy rates in UC and CD. In UC, retrospective studies have reported remission rates between 9.3-80%, which reflects the high variability between the study population, route of administration, mean drug blood levels and the criteria for evaluating response (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Remission rates demonstrated a similar variability ranging from 9.4-75% in clinical trials and prospective studies (1,2,(16)(17)(18)(19).…”

“…The drug was maintained for a median duration of 11 months (IQR [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Ten patients received the drug for at least 12 months.…”

Meconium ileus in cystic fibrosis is not linked to central repetitive region length variation in MUC1, MUC2, and MUC5AC

“…MUC1 is up-regulated and poorly glycosylated in colonic tissue from children with inflammatory bowel disease [10]. Several studies have also reported that MUC5AC plays an important role in inflammatory bowel disease [8, 11]. …”

Prospective comparison of preference and efficacy of adalimumab and infliximab for treating ulcerative colitis naive to antitumor necrosis factor therapy

“…Disease activity before and after anti-TNF-α therapy was measured using the Mayo score [also known as the disease activity index (DAI)] and the EAI. [ 10 , 11 ] Patients were included who had a DAI ≥ 6 points and an EAI ≥ 2 points before the start of anti-TNF therapy. The exclusion criteria were as follows: age less than 20 years, severe infection, severe heart and renal disorders, pregnant or nursing, malignancy, and previous colectomy.…”

“…Cytomegalovirus infection was ruled out by pathological analysis of lesions. [ 11 ] After reading a brief description of IFX and ADA, all of the eligible participants were provided a questionnaire to determine their treatment preference after informed consent was obtained. [ 1 ] According to the protocol, IFX was administered at 5 mg/kg to patients with active UC at weeks 0, 2, and 6, and intravenous IFX injections of 5 mg/kg were administered as maintenance doses every 8 weeks thereafter.…”