Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

Use of Fentanyl Patch for Treatment of Moderate-to-severe Chronic Noncancer Pain: Postmarketing Surveillance of Medical Practice in Japan Using a Risk Minimization Action Plan.

OBJECTIVE: The purpose of this study was to discuss the safety, treatment profile, and clinical effectiveness of 12-month treatment with fentanyl patch (FP), a strong opioid, in medical practice in Japan under the risk minimization action plan (RMAP). METHODS: Patients with moderate-to-severe chronic noncancer pain who had switched to FP from another opioid were registered to take this survey to assess adverse drug reactions (ADRs), therapeutic effect, and pain intensity for up to 12 months. RESULTS: A total of 517 patients were enrolled, and 499 patients (male, 50.9%; mean [SD] age, 63.0 [15.4] years) were included in the safety population. During the 12-month observation period, an ADR occurred in 262 patients (52.5%); most frequent ADRs included nausea (24.2%), somnolence (22.4%), constipation (18.2%), vomiting (9%), and dizziness (4.6%). The prespecified priority survey items, including respiratory depression, drug dependence, and drug withdrawal syndrome, occurred in 2 (both nonserious), 3 (all serious), and 9 (all serious) patients, respectively. In 418 patients from the efficacy population, the response rate was 77.3%, the rate of achievement of the therapeutic goal was 64.5%, and the visual analog scale (VAS) scores for pain severity decreased by 22.3 (26.9) mm. CONCLUSION: Our results identified a reasonable risk-benefit profile for the management of moderate-to-severe chronic noncancer pain in patients previously treated with opioids under long-term treatment with FP under the RMAP. Respiratory depression, drug dependency, and drug withdrawal were rarely observed even under the RMAP in Japan.

Estimation of minimal clinically important change of the Japanese version of EQ-5D in patients with chronic noncancer pain: a retrospective research using real-world data.

BACKGROUND: Quality of life (QoL) is routinely assessed and evaluated in medical research. However, in Japan, there is a lack of solid cutoff criteria for evaluating QoL improvement in chronic noncancer pain management. The present study was conducted to identify the minimal clinically important change (MCIC) of the Japanese version of EuroQol-5D 3L(EQ-5D) utility score and numeric rating scale (NRS) with an emphasis on chronic noncancer pain. METHODS: The data source for this post hoc research was the post-marketing surveillance (PMS) data for a tramadol/acetaminophen combination tablet, which was previously conducted in real-world settings. The parameters extracted from the PMS data were sociodemographic characteristics, NRS, EQ-5D, and dichotomous physician's global impression of treatment effectiveness (PGI). The optimal cutoff points of MCIC for EQ-5D utility and NRS scores were evaluated using receiver operating characteristics (ROC) analysis. An anchor-based approach using PGI was applied. RESULTS: Data of 710 patients with chronic noncancer pain were extracted from the PMS database. The NRS score decreased by 2.7 (standard deviation, 2.3) points, whereas the EQ-5D score increased by 0.16 (0.20) points at 4 weeks from baseline. The changes from baseline in NRS and EQ-5D were significantly correlated (r = 0.53, p < 0.001). The estimated optimal cutoff points of MCIC for EQ-5D and NRS were 0.10 and -2.0 points, respectively. The area under the curve of ROC was > 0.80 in both analyses. CONCLUSION: These results demonstrated novel cutoff criteria for the Japanese version of EQ-5D, focusing on patients with chronic noncancer pain. The obtained criteria were fairly consistent and can be confidently utilized as an evaluation tool in medical research on chronic noncancer pain in Japan, with additional functionality and usability for QoL assessment in pain management practice. TRIAL REGISTRATION: The data source of this post hoc research was a PMS study with the identifier number UMIN000015901 at umin.ac.jp, UMIN clinical trial registry (UMIN-CTR).

The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia.

BACKGROUND: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER) on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia. PATIENTS AND METHODS: Patients with an established diagnosis of schizophrenia were allowed flexible 3-12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS) and on symptomatology using the Clinical Global Impression-Schizophrenia scale. All adverse events (AEs) were also collected. RESULTS: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression-Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS ≥61) also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients had AEs and 8.75% of patients had serious AEs. Despite the recommendation of monotherapy with PAL-ER, 65.84% of patients were given additional antipsychotics (polypharmacy). Post hoc comparisons of monotherapy versus polypharmacy revealed that the monotherapy group had better outcomes and fewer AEs than the polypharmacy treated group. The improvement in social functioning and the rate of socially functional remission did not differ between groups. CONCLUSION: PAL-ER treatment showed effective symptom control and improvement in social functioning. The data suggest that early response to antipsychotic treatment should be important for functional outcomes.

Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: incidence, mortality and clinical characterization.

Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population.