Nozomi Ebata

Somatrogon is a long-acting recombinant human growth hormone approved in several countries, including Japan, for the treatment of children with growth hormone deficiency (GHD). In this study (Clinicaltrials.gov:NCT03874013) Japanese patients with GHD initially received once-weekly somatrogon or once-daily somatropin (0.175 mg/kg/week) for 12 months in the main study period; those who completed the main study were eligible to enroll in a single-arm, 3-year open-label extension (OLE) and receive once-weekly somatrogon (0.66 mg/kg/week). The primary endpoints of the OLE included annualized height velocity (HV), change in height standard deviation score (SDS), and safety. Of 43 patients who completed the main study, 42 continued into the OLE and 40 completed the OLE. Patients were analyzed by treatment received (somatrogon vs. somatropin) during the main study. Mean (SD) HV at OLE baseline was higher in patients originally randomized to somatrogon vs. somatropin (9.78 [1.59] vs. 7.70 [1.10] cm/year); mean HV was similar between original treatment groups for all other OLE timepoints. Mean height SDS increased from main study baseline through the end of the OLE in both treatment groups. During the OLE, 22 (100%) somatrogon-treated patients and 18 (90%) somatropin-treated patients reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild or moderate in severity and no patients discontinued from the OLE or required dose reductions due to TEAEs. Up to 4 years of treatment with once-weekly somatrogon resulted in improved growth response and was well tolerated in Japanese patients with pediatric GHD, including patients who switched to somatrogon from once-daily somatropin.Clinialtrials.gov:NCT03874013

Recombinant human growth hormone (GH; somatropin) treatment has beneficial effects on body composition in patients with Prader-Willi syndrome (PWS). However, this treatment option is limited to children in most countries and to children with short stature in countries such as the USA and Japan. The aim of this multicohort study was to evaluate the effect of somatropin on body composition and to assess its safety in Japanese pediatric and adult participants with PWS. GH-naïve pediatric participants (n = 6) received somatropin 0.245 mg/kg/week, GH-treated pediatric participants (n = 7) received somatropin 0.084 mg/kg/week, and adult participants (n = 20) received somatropin 0.042 mg/kg/week for 1 month, followed by 0.084 mg/kg/week. The study met its primary endpoint in the adult cohort because the least squares mean (95% CI) of the change from baseline to Month 12 in lean body mass (LBM) (%) was greater than the prespecified efficacy criterion of 0. LBM (%) was higher at 12 months in GH-naïve pediatric participants, while GH-treated pediatric participants showed little deterioration in LBM despite reduced GH dosage. Treatment-emergent adverse events (TEAEs) were experienced by five (83.3%), five (71.4%), and 19 (95.0%) participants in the GH-naïve pediatric cohort, GH-treated pediatric cohort, and adult cohort, respectively. Most TEAEs were mild or moderate in severity. Three participants reported four serious TEAEs, and none were treatment related. Somatropin improved body composition in adult participants, enabled maintenance of body composition in pediatric participants, and demonstrated a favorable safety and tolerability profile in all PWS cohorts. (ClinicalTrials.gov ID: NCT04697381)

Background: About one-third of caregivers of pediatric or adolescent growth hormone deficiency (pGHD) patients in Japan have reported poor treatment adherence. However, few studies have examined factors related to adherence for that group. Objective: The aim of this study is to consider factors related to poor adherence to daily treatment among caregivers of pGHD patients in Japan. Methods: A cross-sectional survey was conducted among caregivers of pGHD patients in Japan. Caregivers were asked about demographic and treatment characteristics, health literacy, treatment satisfaction, opinions about treatment, and treatment adherence. Health literacy was assessed using the 14-item health literacy scale (HLS-14). Adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Statistical association with adherence was considered using Chi-square and Student’s t–testing. An exploratory factor analysis (EFA) and K-means cluster analysis was conducted to consider the influence of treatment satisfaction and opinions concerning treatment on adherence. Results: Responses were collected from 112 caregivers. The caregiver’s age being 30– 39 years old, the primary caregiver being male, the primary caregiver being employed, and low functional health literacy for the caregiver were associated with poor adherence. Patients being pre-elementary school age was also associated with poor adherence. Low satisfaction with drug treatment and/or their device and communication with healthcare professionals (HCPs), and lack of agreement with the importance of treatment management (eg, keeping injection records, getting informed about the disease/therapy, reporting non-adherence, and sticking to an administration schedule), were also associated with poor adherence. Conclusion: Strategies to improve treatment adherence among caregivers of pGHD patients in Japan should consider the age, gender, and employment status of the caregiver – as well as their functional literacy. Improvement in satisfaction with the drug or device used, better communication with HCPs, and greater awareness of the importance of treatment management, may also lead to better adherence.

Background and Objectives The guidelines for osteoarthritis (OA) treatment recommend different therapies including pharmacotherapy, and several analgesic options are available for pain management. In Japan, research on hip and knee OA treatment trends is scarce and OA-related healthcare costs are unknown. Therefore, this study aimed to examine the treatment and healthcare cost trends among Japanese patients with hip or knee OA. Methods This was a cross-sectional study held between 2013 and 2019, using a medical claims database. The demographic and treatment characteristics of hip or knee OA patients for each year were descriptively analyzed and the medians for healthcare utilization and all-cause healthcare costs were calculated. Results The yearly mean age of 59,218 hip OA and 270,722 knee OA patients ranged from 66.3 to 68.6 years and 71.1 to 73.1 years, respectively. The prevalence of comorbidities was higher in knee OA than hip OA. In both groups, > 70% of patients were female, and the most common treatment was pain-related medication. In hip OA, topical and systemic nonsteroidal anti-inflammatory drugs (NSAIDs) were mostly used throughout the study period (34.1–41.4% and 32.0–40.3%, respectively). Similarly, in knee OA, topical and systemic NSAIDs were used in 58.3–63.3% and 36.5–46.0% patients, respectively. Increase in the use of acetaminophens (10.9% in hip OA and 10.2% in the knee OA) and weak opioids (3.7%, and 3.4%, respectively) from 2013 to 2019 were observed. Most patients were treated as outpatients in both groups. The median all-cause healthcare costs were approximately 35,000 JPY for hip OA and 74,000 JPY for knee OA. Conclusions Although a considerable change in total healthcare cost was not observed in our study, the contents of medical treatment and cost breakdown were greatly altered due to the treatment and cost for OA itself, and the treatment and cost for comorbidities. Similar studies to investigate such a trend may help predict necessary resources and social needs. Thus, further investigation utilizing other databases is needed.

Purpose: To evaluate the cost-effectiveness of pregabalin versus other analgesics among patients with chronic cervical pain with neuropathic components during routine clinical practice in Japan. Patients and methods: The analysis considered patients with chronic cervical pain with a neuropathic pain component (radiating pain to the upper limb) and who were treated with pregabalin with or without other analgesics (pregabalin-containing treatments) or other analgesics alone (usual care) for 8 weeks. Other analgesics included non-steroidal anti-inflammatory drugs (NSAIDs), weak opioids, antidepressants, and antiepileptic drugs. A Markov cohort simulation model was constructed to estimate costs and effectiveness (in terms of quality-adjusted life-years, QALYs) of each treatment over a 12-month time horizon. In the model, patients transitioned among three states of pain severity (no/mild, moderate, and severe). Data were derived from a previous observational study (pregabalin-containing treatments, n = 138; usual care, n = 211). Cost inputs included medical costs and productivity losses. QALYs were calculated using the EuroQol five-dimensional, five-level questionnaire. The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to assess the robustness of results. Results: From the payer’s perspective, pregabalin-containing treatments were more costly (JPY 61,779 versus JPY 26,428) but also more effective (0.763 QALYs versus 0.727 QALYs) than the usual care, with an ICER of JPY 970,314 per QALY gained. From the societal perspective, which also included productivity losses, the ICER reduced to JPY 458,307 per QALY gained. One-way sensitivity analyses demonstrated the robustness of the results. Given a hypothetical threshold value of one additional QALY of JPY 5,000,000, the probability of pregabalin-containing treatments being cost-effective was 100%. Conclusion: Compared with using other analgesics alone, the use of pregabalin, alone or in addition to other analgesics, was cost-effective for the treatment of chronic cervical pain with a neuropathic pain component in Japan.

Background. Medical costs associated with cardiovascular disease are increasing considerably worldwide; therefore, an efficacious, cost-effective therapy which allows the effective use of medical resources is vital. There have been few economic evaluations of cardiac rehabilitation (CR), especially meta-analyses of medical cost versus patient outcome.Methods. The target population in this meta-analysis included convalescent and comprehensive CR patients with coronary artery disease (CAD), the status most commonly observed postmyocardial infarction (MI). Here, we evaluated medical costs, quality-adjusted life year (QALY), cost-effectiveness, mortality, and life year (LY). Regarding cost-effectiveness analysis, we analyzed medical costs per QALY, medical costs per LY, and the incremental cost-utility ratio (ICUR). We then examined the differences in effects for the 2 treatment arms (CR vs. usual care (UC)) using the risk ratio (RR) and standardized mean difference (SMD).Results. We reviewed 59 studies and identified 5 studies that matched our selection criteria. In total, 122,485 patients were included in the analysis. Meta-analysis results revealed that the CR arm significantly improved QALY (SMD: −1.78; 95% confidence interval (CI): −2.69, −0.87) compared with UC. Although medical costs tended to be higher in the CR arm compared to the UC arm (SMD: 0.02; 95% CI: −0.08, 0.13), cost/QALY was significantly improved in the CR arm compared with the UC arm (SMD: −0.31; 95% CI: −0.53, −0.09). The ICURs for the studies (4 RCTs and 1 model analysis) were as follows: −48,327.6 USD/QALY; −5,193.8 USD/QALY (dominant, CR is cheaper and more effective than UC); and 4,048.0 USD/QALY, 17,209.4 USD/QALY, and 26,888.7 USD/QALY (Conclusions. While there are some limitations, primarily regarding data sources, our results suggest that CR is potentially cost-effective.

Diabetic peripheral neuropathy (DPN) may often be painful. Despite the high prevalence of painful DPN (pDPN) among patients with diabetes mellitus (DM), understanding of its clinical and economic burden is limited. This study aimed to describe the clinical and economic burdens faced by patients with pDPN in Japan, and compared them with those experienced by patients with DPN but without painful symptoms (non-pDPN). This retrospective, observational study used data from a large-scale, hospital-based Japanese claims database collected from April 2008 to June 2015. Comorbidities, clinical departments visited, length of hospital stay, and medical costs for the period of ± 6 months from the diagnosis of pDPN or non-pDPN were described for each group. Glycemic control status was examined for each group for patients with glycated hemoglobin data. The data of 8,740 patients with pDPN (mean age 70.0 years, 53.4% male) and 12,592 patients with non-pDPN (mean age 67.7 years, 55.7% male) were analyzed. Patients with pDPN had more comorbidities than patients with non-pDPN; 48.7% and 30.9% of patients in the respective groups had 20 or more comorbidities. The median length of hospital stay was 5 days longer in patients with pDPN. The median total medical costs were higher in patients with pDPN (\517,762) than in patients with non-pDPN (\359,909). Patients with pDPN spent higher median costs for medications, but the costs for glycemic control drugs were similar in both groups. For 3,372 patients with glycated hemoglobin data, glycemic control was similar between the two groups. Patients with pDPN experienced greater clinical and economic burdens than patients with non-pDPN, suggesting that patients who develop pDPN may suffer not only from the complications of DM and pain, but also from other comorbid disorders.

Except for neurotrophin, no drug had an indication for postherpetic neuralgia (PHN) in Japan prior to pregabalin approval. This approval might have changed PHN treatment patterns. This study aimed to compare PHN treatment patterns and medical costs between patients who started treatment before and after pregabalin approval. Japanese claims data were used to identify patients aged 18 years or more with PHN, postherpetic trigeminal neuralgia or postherpetic polyneuropathy who were initiated on their first PHN‐associated prescription through May 2010 (before approval) or from June 2010 (after approval). From these claims, 6‐month treatment patterns from first prescription were compared for the periods before and after approval. These patterns included pain‐related medications and the frequency of pain‐relief procedures. All‐cause and pain‐related medical costs were also compared for these periods. The number of PHN patients who were initiated on treatment before and after approval were 107 (mean age, 47.4 ± 13.0 years) and 505 (45.9 ± 13.0), respectively. Post‐approval, significant reductions were observed for prescription of non‐steroidal anti‐inflammatory drugs, tricyclic antidepressants and neurotrophin relative to before approval. Excluding pregabalin acquisition costs, mean costs per patient for medications associated with PHN for 6 months from the first prescription were significantly lower after approval, ¥2882 vs ¥4185. Total medical costs were similar in both periods. Approval of pregabalin appeared to result in a treatment paradigm toward use of an approved therapy with demonstrated efficacy.