Use of biologics for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

OBJECTIVES: Limited information is available on the use of biologics in patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) in Japan. The types of biologics, treatment duration, treatment prior to biologics, concomitant treatment, and characteristics of patients receiving biologics were investigated. METHODS: We used a Japanese hospital claims database provided by Medical Data Vision Co. (2008-2021). RESULTS: In the database, 1186 of 34,207 SSc patients (3.5%) and 620 of 12,303 SSc-ILD patients (5.0%) received anti-interleukin-6 (anti-IL-6) drugs, anti-tumour necrosis factor (anti-TNF) drugs, abatacept, or rituximab. The most common were anti-IL-6 drugs [used in 35.5% of SSc patients and 38.5% of SSc-ILD patients (tocilizumab, 34.5% and 36.6%)], followed by anti-TNF drugs [31.3% and 26.5% (etanercept, 10.5% and 9.0%; others, <8%)], abatacept (17.5% and 20.6%), and rituximab (15.7% and 14.4%). Among SSc and SSc-ILD patients treated with anti-IL-6 drugs, anti-TNF drugs, or abatacept, the most common immunosuppressive drugs prior to initiation of biologics were methotrexate and tacrolimus. Approximately half of patients receiving anti-IL-6 drugs, anti-TNF drugs, or abatacept continued treatment beyond 1 year. CONCLUSIONS: Our study indicates that off-label biologics have been used in a certain number of SSc or SSc-ILD patients in Japan, with tocilizumab the most common.

Use of mycophenolate mofetil in patients with pediatric and adult primary nephrotic syndrome: information from a Japanese hospital claims database.

BACKGROUND: Current treatment for frequently relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome focuses on immunosuppressive therapies. Although the clinical guideline suggests the use of mycophenolate mofetil (MMF), limited information is available on patients with primary nephrotic syndrome who receive off-label treatment with MMF in Japan. METHOD: The dose, treatment duration, previous treatment, and characteristics of primary nephrotic syndrome patients receiving MMF were investigated using data from a Japanese hospital claims database (April 2008-September 2021). RESULTS: Data on 424 primary nephrotic syndrome patients receiving MMF (146 patients < 18 years old; 278 patients ≥ 18 years old) were captured. The most common initial daily doses of MMF capsules (% of patients < 18 and ≥ 18 years old) were 1000 mg (31.9%, 36.8%), 1500 mg (16.0%, 23.8%), and 500 mg (23.6%, 17.3%), and the most common maximum daily doses were 1000 mg (43.8%, 32.9%), 1500 mg (23.6%, 28.9%), and 2000 mg (6.3%, 16.2%). Most patients (97.9%, 99.3%) were treated with a daily dose of 2000 mg or less. Among patients < 18 years old, the younger the patient, the lower the dose. MMF was used for more than 1 year in 30.8% of patients < 18 years old and in 28.8% of patients ≥ 18 years old. CONCLUSIONS: Our study suggested that off-label use of MMF for primary nephrotic syndrome has increased since 2012 in Japan. The dose of MMF used in patients with primary nephrotic syndrome was generally within the approved dose range for lupus nephritis and transplant-related diseases in Japan.

Use of mycophenolate mofetil for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

OBJECTIVES: Limited information is available on patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) receiving mycophenolate mofetil (MMF) in Japan. The dose, treatment duration, and patient characteristics of SSc and SSc-ILD patients receiving MMF were investigated. METHODS: We used data from a Japanese hospital claims database (2008-2020). RESULTS: Data on 486 SSc patients ≥18 years old receiving MMF were captured; 314 had SSc complicated with ILD. The most common initial daily doses were 1000 mg (SSc, 39.5%; SSc-ILD, 38.1%) and 500 mg (SSc, 36.6%; SSc-ILD, 34.6%). The most common maximum daily doses were 1000 mg (SSc, 33.3%; SSc-ILD, 34.9%), 1500 mg (SSc, 24.4%; SSc-ILD, 23.1%), and 2000 mg (SSc, 23.8%; SSc-ILD, 24.4%). Doses ranged from 250 to 3000 mg/day and were similar for SSc and SSc-ILD patients. Over 27% of patients received treatment for >1 year. There was a gradual decrease in steroid doses during MMF treatment. CONCLUSIONS: Our study suggests that the off-label use of MMF for SSc and SSc-ILD has been increasing annually since 2015 in Japan. The doses used in patients with SSc and SSc-ILD were similar to the approved doses of MMF for lupus nephritis in Japan.

[Usefulness of Dilution for Rapid Simultaneous Determination of Residual Pesticides in Agricultural Products by LC-MS/MS].

A rapid, easy and versatile, simultaneous analytical method by LC-MS/MS based on extraction of QuEChERS method (EN 15662:2008) was developed for the determination of residual pesticides in agricultural products. In this method, it allowed to prepare a test solution only dilution without purification using solid phase extraction column. The method was assessed for 210 pesticide residues in 21 kinds of vegetables and fruits at the fortification levels of 0.01 and 0.1 µg/g according to the method validation guideline (Ministry of Health, Labour and Welfare of Japan). As a result, 194 to 210 analytes met the management criteria of the guideline. Thus, the present method could be useful for a rapid simultaneous determination of residual pesticides in agricultural products.

Effects of maternal exposure to a low dose of diethylstilbestrol on sexual dimorphic nucleus volume and male reproductive system in rat offspring.

Diethylstilbestrol (DES) was administered subcutaneously at 0.5, 1.5 or 4.5 microg/kg/day (DES 0.5, 1.5 and 4.5 groups, respectively) to pregnant SD rats daily on days 7-21 of gestation, to investigate its effects on the development and functions of the reproductive system in their male offspring. Of the 10 pregnant rats in the DES 4.5 group, only 1 delivered, and this rat could not suckle the pups. Rat pups in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. The testosterone concentrations in the DES 1.5 and 0.5 groups at 6 weeks were significantly decreased and the plasma LH concentrations were not altered. In the DES 1.5 group, DES treatment did not change the volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) in the male offspring, although this dose of DES increased the volume of SDN-POA in female offspring. The DES treatment altered frequencies in the cycles of the seminiferous tubules, and suppressed histological maturation in the epididymis and the prostate weight. These observations indicate that prenatally administered DES impairs testicular endocrine function continuously as well as pituitary function, but the induced low level of testosterone disrupts spermatogenesis and permanently inhibits the morphological development of epididymis and prostate.

Effects of maternal exposure to diethylstilbestrol on the development of the reproductive system and thyroid function in male and female rat offspring.

Diethylstilbestrol (DES) was administered subcutaneously at 1.5 or 15 microg/kg/day (DES 1.5 group, DES 15 group) to pregnant SD rats daily on days 7-21 of gestation to investigate its effects on the development and functions of the reproductive system and thyroid gland in their offspring. Of the 11 pregnant rats in the DES 15 group, only one delivered a live pup. Rat pups in the DES 1.5 group were autopsied at 1, 3, or 6 weeks after birth. In the DES 1.5 group, the plasma T4 concentrations at all weeks of age at autopsy were significantly increased, the TSH concentration at 6 weeks of age was also significantly increased, and the height of thyroid follicular epithelial cells was increased at 3 weeks. The testosterone concentration in the DES 1.5 group at 6 weeks was significantly decreased and the plasma LH concentration was increased. The DES treatment increased the plasma FSH concentration in female pups at 3 weeks, increased the percentages of primary and secondary ovarian follicles, and decreased the percentage of primordial follicles, but did not influence the timing of the vaginal opening or the onset of the estrous cycle. These observations indicate that prenatally administered DES increases thyroid function, and has an inhibitory effect on testicular function and a promoting effect on female reproductive function.