Treatment of refractory polyarticular juvenile idiopathic arthritis with tacrolimus

2019

Exp Ther Med

Previously, few studies have reported treatment with tacrolimus (TAC) for patients with systemic-onset juvenile idiopathic arthritis (SOJIA). The aim of the current study was to investigate the effect of TAC on patients with SOJIA. Data were collected from the beginning of treatment with TAC to the 12-month endpoint, which was defined as the last follow-up. Clinical characteristics included sex, age, duration of the disease, TAC dose, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), hemoglobin (Hb), platelet (PLT) and white blood cell (WB) levels, prednisolone (PDN) dose and interleukin-6 (IL-6) expression. The baseline characteristics of the patients were: ESR, 67.8±18.7 mm/h; CRP, 128.0±38.9 mg/l; Hb, 108.7±13.7 g/l; PLT, 416.8±90.1×109/l; WB, 26.0±10.2×109/l; PDN dose, 49.0±17.1 mg/day. Following 12 months of treatment with TAC, ESR, CRP, PLT and WB levels, and the dose of PDN required for the treatment of patients with SOIJA were all decreased compared with the baseline values. No serious adverse reactions were reported. Therefore, TAC could be an effective treatment for SOJIA.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment of patients with systemic‑onset juvenile idiopathic arthritis with tacrolimus

2019

Exp Ther Med

“…Furthermore, it has been demonstrated that tacrolimus may be used to improve the outcome of patients who undergo bone marrow (35)(36)(37)(38)(39)(40)(41)(42), lung (43) and heart transplantation (44). In previous years, clinical experiments have also indicated that tacrolimus has useful applications in systemic-onset juvenile idiopathic arthritis (45)(46)(47)(48), nephrotic syndrome (49)(50)(51)(52)(53)(54)(55), SLE (56)(57)(58)(59)(60)(61)(62)(63)(64)(65), myasthenia gravis (66,67), ulcerative colitis (68,69) and autoimmune hepatitis (70). Furthermore, according to a previous review article, tacrolimus is a safe and effective agent for treating patients with LN (10).…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real‑world data

et al. 2020

Exp Ther Med

The present study aimed to establish a population pharmacokinetics model of tacrolimus and further optimize the initial dosing regimen of tacrolimus in pediatric and adolescent patients with lupus nephritis (LN). Pediatric and adolescent patients with LN were recruited between August 2014 and September 2019 at the Children's Hospital of Fudan University (Shanghai, China). Relevant information was used to set up a population pharmacokinetics model with a Nonlinear Mixed Effect Model and the initial dosage regimen was simulated with the Monte Carlo method. Body weight and co-administration of wuzhi capsule were indicated to influence tacrolimus clearance in pediatric and adolescent patients with LN, and at the same body weight, the rate of tacrolimus clearance in patients without vs. with co-administration of wuzhi capsule was 1:0.71. In addition, in patients who were not administered wuzhi capsule, an initial dosage regimen of 0.15 mg/kg/day was recommended for a body weight of 10-23 kg and 0.10 mg/kg/day for 23-60 kg; in patients who were administered wuzhi capsule, an initial dosage regimen of 0.10 mg/kg/day was recommended for a body weight of 10-23 kg and 0.05 mg/kg/day for 23-60 kg. To the best of our knowledge, the present study was the first to establish a population pharmacokinetics model of tacrolimus in order to determine the optimal initial dosage regimen of tacrolimus in pediatric and adolescent patients with LN.

“…Tacrolimus also plays an active role in treatments for nephrotic syndrome, [27][28][29][30][31][32][33] systemic-onset juvenile idiopathic arthritis [34][35][36][37] and other disorders. Tacrolimus has been used to treat paediatric systemic lupus erythematosus, [38][39][40][41][42][43][44][45][46][47] but with considerable pharmacokinetic variation between individuals.…”

Section: What Is K Nown and Objec Tive Smentioning

confidence: 99%

Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on theCYP3A5polymorphism and coadministration with Wuzhi capsule

et al. 2019

J Clin Pharm Ther

What is known and objectives Tacrolimus, an immunosuppressant, has been used to treat paediatric systemic lupus erythematosus, but the optimal initial regimen is not clear. The purpose of this study was to explore the optimal initial dose of tacrolimus for children with systemic lupus erythematosus using population pharmacokinetics and pharmacogenomics. Methods Clinical information, tacrolimus concentrations and related genetic polymorphisms were incorporated into a model using non‐linear mixed‐effects modelling (NONMEM) analysis. Results and discussion The results showed that weight, the CYP3A5 genotype and combined treatment with Wuzhi capsule can affect tacrolimus clearance in children with systemic lupus erythematosus. Furthermore, at the same weight, the ratios of tacrolimus clearance were 1:2.49:0.57:1.4193 from people who were CYP3A5*3/*3 and did not take Wuzhi capsule, people who had the CYP3A5*1 allele and did not take Wuzhi capsule, people who were CYP3A5*3/*3 and took Wuzhi capsule, and people who had the CYP3A5*1 allele and took Wuzhi capsule, respectively. In addition, we found that 0.10 mg/kg split into two doses was suitable for people with weights from 10 to 60 kg who were CYP3A5*3/*3 and did not take Wuzhi capsule, who were CYP3A5*3/*3 and took Wuzhi capsule, and who had the CYP3A5*1 allele and took Wuzhi capsule. In people who had the CYP3A5*1 allele and did not take Wuzhi capsule, 0.15 mg/kg split into two doses was appropriate for those with weights from 10 to 40 kg and 0.10 mg/kg split into two doses was appropriate for those with weights from 40 to 60 kg. What is new and conclusion This study is the first study to recommend an optimal initial regimen of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration of Wuzhi capsule.