A Retrospective Cohort Study of Clinical Features and Treatment Patterns With Ustekinumab in Patients With Crohn Disease Utilizing a Health Care Database in Japan.

BACKGROUND: Biologics are used to treat moderate-to-severe Crohn disease (CD). In Japan, ustekinumab was approved for reimbursement for CD treatment in 2017. However, limited information describes utilization of ustekinumab in real-world settings. OBJECTIVE: To describe treatment patterns and clinical outcomes of patients with CD treated with ustekinumab in Japan. METHODS: A retrospective cohort drug utilization study was conducted using the Japan Medical Data Center employment insurance database. Patients with a diagnosis of CD who initiated treatment with ustekinumab (International Classification of Disease, Tenth Revision [ICD-10] K50.x) from January 1, 2017, to September 30, 2020, were enrolled. Eligible patients were followed up until disenrollment or study end (September 30, 2020). RESULTS: A total of 622 patients with CD initiated ustekinumab during the study period; 45.7% had no prior history of biologic use (bio-naive) and 54.3% had previously received ≥1 biologic (bio-experienced); 82.8% of patients received an induction dose of whom 97.5% received a dose within the recommended range (260-520 mg) and 90.8% of patients received their first maintenance dose within a 42- to 70-day interval. Median treatment duration was 14.8 months and 90.2% remained on ustekinumab at study end. Compared with the 12-month period prior to ustekinumab initiation, surgical procedures decreased by 88.0%, gastrointestinal complications by 64.6%, enteral nutrition requirements by 41.9%, and CD-related hospitalizations by 62.6% within 12 months after commencing ustekinumab. CONCLUSIONS: These first real-world data from Japan, where ustekinumab has been used longest for CD treatment, shows that a majority of patients initiated ustekinumab as per the recommended label. Indirect evidence of clinical impact could be relevant in other settings in Asia.

The incidence of thrombosis with co-occurring thrombocytopenia prior to the SARS-CoV2 pandemic: A population-based study.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare prothrombotic disorder that is a safety concern for some COVID-19 vaccines. We aimed to devise a case definition to estimate the incidence of thrombosis with thrombocytopenia as a proxy for TTS in a national insurance claims database. METHODS: We conducted a retrospective observational study using the National Health Insurance Research Database (NHIRD) in Taiwan over the three-year period prior to the SARS-COV-2 pandemic (2017-2019). Our case definition was all patients with newly diagnosed thrombosis co-occurring with a diagnosis of thrombocytopenia within seven days before or after the thrombosis diagnosis. Cases were identified using International Classification of Disease-10 codes. FINDINGS: We identified 2010 patients with newly diagnosed thrombosis co-occurring with thrombocytopenia during the study period. The mean age was 64.71 years; female:male ratio 1:1.45. The most frequent thrombotic events were coronary artery disease (18.81%), cerebral infarction (16.87%), and disseminated intravascular coagulation (13.13%). Cerebral venous sinus thrombosis was rare (<0.1%). The average annual incidence rate of co-occurring new diagnoses of thrombosis and thrombocytopenia was 2.84 per 100 000 population. Incidence rates were higher in men than women, except in 20-39 year-olds (higher in females). 20.6% of patients died within the first month after diagnosis. INTERPRETATION: We observed that the demographic and clinical characteristics of thrombosis with co-occurring thrombocytopenia using our case definition is different from that of TTS. Further research is needed to refine the case definition of TTS in the post-COVID-19 vaccination period.

Characteristics and risk of interstitial lung disease in dermatomyositis and polymyositis: a retrospective cohort study in Japan.

Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42-20.59) for dermatomyositis and 5.39 (95% CI 4.43-6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18-3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.

Persistence and Adherence to Biologics in Patients with Psoriasis in Taiwan: A New Biologics User Cohort Study.

Background: Biologics are used to treat moderate-to-severe psoriasis, and persistence to biologics may reflect clinical effectiveness. Limited information describing how biologics are used in patients with moderate-to-severe psoriasis in Asian countries is available. We conducted a population-based, retrospective, new user cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan to assess treatment persistence and adherence to biologics. Methods: Adults with a diagnosis of psoriasis between 01 January 2015 and 31 December 2017 were identified in the NHIRD (ICD-9-CM 696.1; ICD-10 L40.0). New users were patients who initiated treatment with etanercept, adalimumab, ustekinumab or secukinumab between 01 January 2015 and 31 December 2017. All eligible patients were followed until 31 December 2018, death or disenrollment. Kaplan-Meier analysis was conducted to estimate persistence of treatment for index biologics. A Cox-proportional hazard regression model was used to compare risks of biologic discontinuation between biologic groups. Adjustments for potential confounding factors (age, gender and Charlson comorbidity index score) were made in the Cox model. Results: There were 1,397 new biologic users with psoriasis during the study period. The ratio men:women was approximately 4:1. Mean age of patients ranged from 44.6 to 47.7 years across exposure groups. The 1-year/2-years persistence rates were 94.2%/84.9% for ustekinumab, 96.2%/not calculated (due to too few patients at year 2) for secukinumab, 66.0%/29.9% for etanercept, and 59.8%/40.3% for adalimumab. The risk of discontinuation was significantly lower in patients initiating ustekinumab compared with adalimumab (hazard ratio adjusted for age, sex and co-morbidities 0.289, 95%CI 0.247-0.339, p < 0.0001). Drug survival was significantly higher for ustekinumab compared with adalimumab and etanercept (log-rank test p < 0.0001). The proportions of patients with 1-year/2-years medication possession ratios of ≥80% were 95.3%/92.0% for ustekinumab, 98.1%/not calculated for secukinumab, 89.4%/83.1% for etanercept, and 70.8%/59.4% for adalimumab. Limitations: Clinical improvement and response to treatment data were not available. Conclusion: There was relatively high persistence amongst biologic users with psoriasis in Taiwan. There is a trend towards greater persistence of ustekinumab compared to other biologics, the magnitude of which depends on the treatment gap used for its calculation. This study provides real-world evidence that may facilitate optimal treatment choice.

A population-based cohort study of the epidemiology of light-chain amyloidosis in Taiwan.

The incidence rate of AL (light-chain) amyloidosis is not known in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to estimate incidence and all-cause case fatality rates, and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed, newly diagnosed AL amyloidosis from 01-Jan-2016 until 31-Dec-2019 were enrolled and followed up until dis-enrolment, death or study end (31-Dec-2019). There were 841 patients with newly diagnosed AL amyloidosis with median age of 61.4 years and 58.7% were men. At diagnosis, cardiac, renal and liver-related diseases were present in 28.54%, 23.19% and 2.14% of patients, respectively. AL amyloidosis age-adjusted annual incidence was 5.73 per million population in 2016 and 5.26 per million population in 2019. All-cause case fatality ranged from 1.7 to 2.9% over the study period and was highest (~10%) in patients ≥ 80 years. Survival was significantly lower in patients with co-morbid cardiac, renal, or liver-related diseases which could indicate organ involvement. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries. The poor prognosis in patients with co-morbid diseases highlights the need for earlier diagnosis.

Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan.

BACKGROUND: Long-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics. METHODS: Patients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency. RESULTS: There were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94-9.11) and 9.93 (5.88-15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32-2.99) and 3.10 (1.14-6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide. DISCUSSION: No increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.