BACKGROUND: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions. METHODS: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28. RESULTS: Two hundred and ninety-one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p < 0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period. CONCLUSION: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients.
Administration, Topical ; Adult ; Child ; Dermatitis, Atopic* ; Eczema ; Extremities ; Humans ; Korea ; Neck ; Skin ; Tacrolimus*

The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.
Adult ; Drug Therapy, Combination/methods ; Female ; Graft Rejection/diagnosis/*etiology/*prevention & control ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/administration & dosage/adverse effects ; Kidney Transplantation/*adverse effects ; Longitudinal Studies ; Male ; Middle Aged ; Sirolimus/*administration & dosage/adverse effects ; Survival Rate ; Tacrolimus/*administration & dosage/adverse effects ; Treatment Outcome

OBJECTIVETo assess the efficacy and safety of topical tacrolimus for erosive oral lichen planus (EOLP).

METHODSLiteratures published up to December 2013 were searched from PubMed, Embase, CENTRAL, Chinese BioMedical Literature Database (CBM), and System for Information on Grey Literature in Europe (SIGLE). All randomized controlled trials (RCTs) of topical tacrolimus for EOLP which compared with other interventions or a placebo were considered in this Meta-analysis. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane Handbook and the materials were analyzed with the software Revman 5.2.5. The primary outcome measures were the symptoms (e.g. pain, discomfort) complained by patients. The secondary outcome measures included the improvement rate of clinical signs assessed by the investigators and the incidence of adverse effects (e.g. clinical candidiasis).

RESULTSA total of 9 RCTs involving 476 patients were finally included. The pooled odds ratio (OR) of clinical improvement for topical tacrolimus vs. topical corticosteroids was 1.19 [95% confidence interval (CI): 0.64-2.22, I2: 44%]. Regarding to 0.1% tacrolimus and 0.03% tacrolimus, the pooled OR were 1.87 (95% CI: 0.60-5.82) and 1.47 (95% CI: 0.14-16.04) respectively in subgroup analysis. No serious adverse events were reported in topical tacrolimus group.

CONCLUSIONSThere was no evidence to support that topical tacrolimus for EOLP was more effective and safer than topical corticosteroids in this Meta-analysis. Clinical assessment criteria should be established and accepted by clinicians and researchers before further RCTs are undertaken.

Administration, Topical ; Humans ; Immunosuppressive Agents ; administration & dosage ; Lichen Planus, Oral ; drug therapy ; Randomized Controlled Trials as Topic ; Tacrolimus ; administration & dosage ; adverse effects

OBJECTIVETo summarize the clinical characteristics, early diagnosis, comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.

METHODData of 6 cases with PTLD seen between January 2011 and December 2013 were retrospectively analyzed. The anti-rejection drug dose adjustments, the effect of rituximab, antiviral therapy and comprehensive treatment program after surgery were explored.

RESULT(1) The diagnosis of PTLD was confirmed by histologic findings. Six cases of PTLD including 3 males and 3 females were diagnosed as congenital biliary atresia and underwent split liver transplantation. The occurrence rate of PTLD was 2.9%. (2) The median time to the development of PTLD was less than 6 months. The initial symptom of PTLD in all patients was fever and clinical manifestations of PTLD were non-specific, depending on the involving organs. Five cases of PTLD developed gastrointestinal symptoms, including diarrhea, abdominal pain, and abdominal distension. One case developed respiratory symptoms, including cough and tachypnea. Three cases had lymph node involvement. In 2 cases pathophysiology involved polymorphic lymphocyte proliferation and in 4 cases B lymphocyte proliferation. (3) Two cases died, in whom EBV DNA was not detected and were diagnosed as PTLD by surgical pathology before death. Four survived cases had high EBV-DNA load and then were diagnosed as PTLD by biopsy pathology. (4) Of the 6 cases of PTLD, 2 cases died and 4 cases survived. The overall mortality was 33%. The dead cases were only treated with laparotomy because of intestinal obstruction or perforation and the survived cases were treated with tacrolimus at reduced doses or discontinuation and rituximab. In 2 cases antiviral therapy (acyclovir) was continued, including 1 cases of intestinal obstruction treated with surgical repair. All the survived patients were followed up for 4 months to 1 year and no evidence has been found.

CONCLUSIONEBV infection is the high risk factor for PTLD after liver transplantation. Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD. Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD. A reduction in the dose of tacrolimus is suggested. Operation therapy can also play a role in the management of local complications.

Antiviral Agents ; administration & dosage ; Biliary Atresia ; therapy ; DNA, Viral ; analysis ; Drug Therapy, Combination ; Early Diagnosis ; Epstein-Barr Virus Infections ; diagnosis ; therapy ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Infant ; Liver Transplantation ; adverse effects ; Lymphoproliferative Disorders ; diagnosis ; etiology ; mortality ; therapy ; Male ; Pediatrics ; Postoperative Complications ; Retrospective Studies ; Survival Rate ; Tacrolimus ; administration & dosage

PURPOSE: The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. MATERIALS AND METHODS: This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. RESULTS: Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). CONCLUSION: Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.
Adult ; Drug Administration Schedule ; Female ; Graft Rejection/drug therapy/prevention & control ; Humans ; Immunosuppressive Agents/*administration & dosage/adverse effects/therapeutic use ; *Kidney Transplantation ; Male ; Middle Aged ; Safety ; Tacrolimus/*administration & dosage/adverse effects/therapeutic use

BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
Acute Disease ; Adult ; Antiviral Agents/therapeutic use ; BK Virus/*physiology ; Creatinine/blood ; Female ; *Graft Rejection/diagnosis/virology ; Humans ; Immunosuppressive Agents/administration & dosage ; Kidney/*virology ; Kidney Diseases/pathology/surgery/*virology ; *Kidney Transplantation ; Male ; Middle Aged ; Polyomavirus Infections/drug therapy/*etiology/pathology ; Retrospective Studies ; Tacrolimus/administration & dosage ; Time Factors ; Transplantation, Homologous/adverse effects ; Tumor Virus Infections/drug therapy/*etiology/pathology

PURPOSE: To determine whether topical tacrolimus might prove effective in the treatment of refractory anterior segment inflammatory diseases, and to evaluate its efficacy in eyes with ocular graft versus host disease (GVHD), and vernal keratoconjunctivitis (VKC). METHODS: Twenty-eight eyes of 14 patients with anterior segment inflammation refractory to steroid treatment were treated with 0.03% tacrolimus ointment at the Samsung Medical Center, Seoul, Korea from March 2008 through August 2009. Seven patients had ocular GVHD and seven had VKC. We evaluated the conjunctival and corneal inflammatory change at one, two, four, and eight weeks after treatment with a scoring system. Time to initial response of treatment and therapeutic effect between GVHD and VKC was also analyzed. After the eight-week treatment period, patients were divided into two groups (maintenance group and discontinuance group). Eight patients maintained the treatment for an additional four months, and six patients discontinued the treatments. Therapeutic effect was also compared between the groups at eight weeks and six months after treatment. RESULTS: The mean conjunctival and corneal inflammation score was reduced significantly at eight weeks after treatment (p < 0.0001). The therapeutic effect in conjunctival inflammation was first noted at week two after the initial treatment (p = 0.002); reduction in corneal inflammation was first noted at one week (p = 0.0009). When compared according to diagnosis, no therapeutic difference was detected between the groups (p > 0.05). Six months after treatment, we noted no therapeutic differences between the maintenance group and discontinuance group (p > 0.05). CONCLUSIONS: 0.03% tacrolimus ointment was safe and effective for use in anterior segment inflammatory disease refractory to steroid.
Administration, Topical ; Adolescent ; Adult ; Child ; Conjunctivitis, Allergic/*drug therapy ; Female ; *Graft vs Host Disease ; Humans ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Ointments ; Prospective Studies ; Statistics, Nonparametric ; Tacrolimus/*administration & dosage ; Treatment Outcome

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).
Adult ; Alleles ; Cytochrome P-450 CYP3A ; genetics ; Digestive System Diseases ; chemically induced ; Dose-Response Relationship, Drug ; Female ; Genotype ; Graft Rejection ; genetics ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; blood ; therapeutic use ; Kidney Transplantation ; Male ; Middle Aged ; Polymorphism, Genetic ; Retrospective Studies ; Tacrolimus ; administration & dosage ; adverse effects ; blood ; therapeutic use

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.
Algorithms ; Bayes Theorem ; Database Management Systems ; Drug Monitoring ; methods ; Humans ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Kidney Transplantation ; Models, Biological ; Tacrolimus ; administration & dosage ; pharmacokinetics

OBJECTIVETo analyze and evaluate the efficacy and safety of tacrolimus and low-dose steroids in the treatment of steroid-resistant nephrotic syndrome in children.

METHODTwenty-one children with steroid-resistant nephrotic syndrome enrolled from October 2008 to July 2010 into this retrospective longitudinal study received oral tacrolimus treatment, 0.1 to 0.15 mg/kg per day and once every 12 hours, and prednisone 0.2 to 0.75 mg/kg per day simultaneously. During the treatment, the plasma concentration of tacrolimus, urine volume, urine, serum creatinine and liver function were regularly monitored.

RESULTAfter 1 to 3 months treatment, 14 cases showed complete remission and 7 cases had partial remission. Sixteen patients received renal biopsy, of whom 6 revealed minimal change nephropathy with complete remission in 3 cases, 3 cases had partial remission;4 cases revealed focal segmental glomerulosclerosis with 2 complete remission and 2 partial remission; other 5 children with IgM nephropathy and 1 mesangial proliferative glomerulonephritis achieved complete remission. Within treatment period, 6 patients presented transient adverse reactions, without altering the principle treatment strategy, but only taking the symptomatic treatment. During follow-up, 1 case was lost to follow-up and the remaining 20 cases were followed up from 2 months to 21 months. In 4 patients the disease relapsed within 1st-year follow-up, while at 2nd-year follow-up, 4 cases had (6 times) recurrence.

CONCLUSIONTacrolimus showed a reliable effect in children with steroid-resistant nephrotic syndrome. Less adverse reactions were seen, and most of them could be tolerated. Nevertheless, the patients had a higher relapse rate after 1 to 2 years treatment. Therefore, the long-term effects of tacrolimus for steroid-resistant nephrotic syndrome remains to be further evaluated.

Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Humans ; Infant ; Longitudinal Studies ; Male ; Nephrotic Syndrome ; drug therapy ; Prednisone ; administration & dosage ; therapeutic use ; Retrospective Studies ; Tacrolimus ; administration & dosage ; therapeutic use ; Treatment Outcome