Use Of Tacrolimus In Patients Research Articles

P716 The use of tacrolimus in patients with ulcerative colitis resistant to standard medical therapy

P716 The use of tacrolimus in patients with ulcerative colitis resistant to standard medical therapy

PWE-056 Five year prospective study of the use of tacrolimus in patients with refractory subacute ulcerative colitis: final report

<h3>Introduction</h3> The management of moderately active ulcerative colitis (UC) refractory to standard medical treatment remains a challenge. NICE²recommends tacrolimus as one of the treatment options in refractory disease. Previously we reported our experience of tacrolimus in the first 17 patients, 7 of whom remained well. Here we provide our latest results. <h3>Method</h3> Prospective data was collected from January 2010–January 2015 on all patients with UC who were refractory to, or intolerant of, standard therapy and were started on oral tacrolimus (Prograf). Initial dosing was 0.1 mg/kg/day in 2 divided doses; monitoring was undertaken following a local policy with blood testing and tacrolimus trough levels at week 2, 4 and at 3 monthly intervals thereafter. A target trough level between 5–20 ng/ml was maintained, with dosing adjusted accordingly. Clinical response was assessed by one consultant gastroenterologist (AWH) in clinic. <h3>Results</h3> A total of 34 patients were treated with oral tacrolimus over the 5 year period. Of these, 17 (50%) demonstrated a clinical response, however only 10 (29%) of these tolerated the drug. Of the 10 patients who continued on tacrolimus the median duration of treatment was 7 months (range 2–60 months). Reasons for intolerance included renal impairment (n = 4), hypertension (n = 2), nausea and headache, which resulted in cessation of treatment. Therefore at the end of the 5 year period only 10 of 34 (29%) patients continued on treatment with tacrolimus. Of the 24 who were either non-responders or intolerant, 15 (63%) underwent colectomy and 9 received treatment with methotrexate, a biological agent or alicaforsen. <h3>Conclusion</h3> This 5 year prospective audit using tacrolimus in patients with refractory UC in a general hospital outpatient setting has shown that with careful monitoring the drug may be used safely with a clinical response in about a third of patients for up to 60 months. Our findings are similar to those from tertiary centres where clinical remissions of 44%⁴and 20%⁵were reported. No long term adverse events to date have been reported in this group however close monitoring is essential. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Dhillon AS, Harris AW. Gut. 2014;<b>63</b>(Suppl 1):A63 NICE. 2013 UC:CG166 Ogata H, <i>et al</i>. <i>Gut</i>. 2006;55(9):1255-62 Landy J, <i>et al</i>. <i>JCC</i>. 2013;(7):e516-e521 Lena W, <i>et al</i>. IBD. 2013;19:1490–1498

PTU-063 A Prospective Audit Of The Use Of Tacrolimus In Patients With Refractory Subacute Ulcerative Colitis In A District General Hospital

IntroductionTacrolimus appears to be effective short-term treatment for patients with refractory ulcerative colitis (UC)1 and is recommended by NICE2 in suitable patients. We report our experience in a district general...

Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs—a multicenter, double-blind, parallel-group trial

In this trial, we investigated the safety and efficacy of tacrolimus used in addition to standard antirheumatic drugs in patients with rheumatoid arthritis. Tacrolimus 3 mg or placebo was orally administered once daily for 52 weeks in a double-blind manner to patients with early active rheumatoid arthritis receiving other disease-modifying antirheumatic drugs (DMARDs). A total of 123 patients were randomized to the tacrolimus group (61 patients) and to the placebo group (62 patients). In the tacrolimus group, 70.5% achieved a clinical response according to American College of Rheumatology (ACR) 20 criteria, whereas 45.2% in the placebo group did so (P = 0.005). The tacrolimus group also showed significant improvement in terms of the European League Against Rheumatism (EULAR) response criteria of “good or moderate” versus the placebo group (86.9 vs. 56.5%, respectively). Likewise, significantly more patients in the tacrolimus group versus the placebo group achieved remission of the Disease Activity Score in 28 joints (DAS28) (45 vs. 21%). The mean changes in the Total Sharp Score and erosion score were lower in the tacrolimus group, but the differences between the two groups were not significant. There was no significant difference between the two groups in the incidence of adverse events. Based on these results, we can conclude that the additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to other DMARD treatments is useful, and this could become one of the treatment options for these rheumatoid arthritis patients.

Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs—a multicenter, double-blind, parallel-group trial

In this trial, we investigated the safety and efficacy of tacrolimus used in addition to standard antirheumatic drugs in patients with rheumatoid arthritis. Tacrolimus 3mg or placebo was orally administered once daily for 52weeks in a double-blind manner to patients with early active rheumatoid arthritis receiving other disease-modifying antirheumatic drugs (DMARDs). A total of 123 patients were randomized to the tacrolimus group (61 patients) and to the placebo group (62 patients). In the tacrolimus group, 70.5% achieved a clinical response according to American College of Rheumatology (ACR) 20 criteria, whereas 45.2% in the placebo group did so (P=0.005). The tacrolimus group also showed significant improvement in terms of the European League Against Rheumatism (EULAR) response criteria of "good or moderate" versus the placebo group (86.9 vs. 56.5%, respectively). Likewise, significantly more patients in the tacrolimus group versus the placebo group achieved remission of the Disease Activity Score in 28 joints (DAS28) (45 vs. 21%). The mean changes in the Total Sharp Score and erosion score were lower in the tacrolimus group, but the differences between the two groups were not significant. There was no significant difference between the two groups in the incidence of adverse events. Based on these results, we can conclude that the additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to other DMARD treatments is useful, and this could become one of the treatment options for these rheumatoid arthritis patients.

Pharmacokinetics of tacrolimus in liver transplant patients*

To characterize the pharmacokinetics of the immunosuppressive agent tacrolimus (FK 506) in liver transplant patients. Patients (n = 16) were assessed during and after 1- to 3-day intravenous infusions followed by a 2-week course of oral dose therapy. Plasma and whole blood data were fitted simultaneously with equations accounting for nonlinear drug binding by red blood cells to generate clearance (CL) and volume of distribution (V). The maximum blood/plasma ratio of tacrolimus was 55.5 +/- 26.8 (SD) and half-life averaged 12.1 +/- 4.7 hours. The CL and V were relatively high based on plasma concentrations (CL, 1.7 L/hr/kg; V, 30 L/kg) and low based on whole blood (CL, 54 ml/hr/kg; V, 0.9 L/kg), with moderate variability (coefficient of variation, 34% to 49%) among the patients. Correlations of plasma CL and V with maximum blood/plasma ratios (ranging from 13 to 114) were strong (r = 0.65 and r = 0.73). Blood binding affects the disposition of tacrolimus, and plasma concentrations are indirectly and inversely related to red cell binding. The oral dose data for tacrolimus yielded a brief absorption lag time (tlag, 0.39 hour), a variable first-order absorption rate constant (ka, 4.5 +/- 3.0 hr-1), and consistent bioavailability (F, 25% +/- 10%). The area under the concentration-time curve versus 12-hour minimum concentration relationships for both whole blood and plasma were nearly linear, confirming the utility of trough values for monitoring drug exposure. This study provides pharmacokinetic guidelines for the use of tacrolimus in patients undergoing hepatic transplantation. Nonlinear blood binding is a major source of interpatient variation in the disposition of tacrolimus.