Real-world Clinical Setting In Japan Research Articles

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. In this study, 2236 patients with mTNBC (median age 66.0years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Long-Term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis in Japan: 10-Year Analysis of the Real-World TRUST Study.

To assess the long-term safety and effectiveness of tacrolimus as maintenance therapy in patients with lupus nephritis (LN) receiving treatment in real-world clinical settings in Japan. An open-label, noncomparative, observational, prospective postmarketing surveillance study was conducted in 1395 patients with LN receiving maintenance treatment with tacrolimus at 278 medical institutions across Japan over a period of 10 years. Tacrolimus continuation rate and cumulative incidence of adverse drug reactions (ADRs), relapse, progression to renal failure, and progression to dialysis were calculated using Kaplan-Meier analysis. Safety data were available for 1355 patients, almost half (49.3%) of whom remained on tacrolimus for the full 10 years of follow-up. A significant reduction in mean (SD) daily oral corticosteroid dose was observed from 16.0 (9.7) mg/day at 4 weeks after initiation of tacrolimus treatment to 7.2 (4.4) mg/day at year 10 (P < 0.001). The most frequently reported serious ADRs were infections (reported for 131 [9.7%] patients). Except for infections, no marked increase in the incidence of any other ADRs was seen over time, including renal impairment, malignant tumors, and cardiac dysfunction. Renal function was generally well maintained over the 10 years of follow-up. At year 10, cumulative rates of relapse, renal failure, and dialysis were 44.5%, 12.2%, and 4.5%, respectively. Tacrolimus was effective and generally well tolerated as maintenance therapy for LN in a large cohort of patients in Japan followed for 10 years, almost half of whom remained on therapy for the entire duration of follow-up. (ClinicalTrials.gov: NCT01410747).

Real-World Amount of Clotting Factor Concentrates Dispensed and Annual Medical Expenditures for Japanese Patients with Hemophilia B.

Until extended half-life (EHL) factor IX (FIX) concentrates became available in Japan in 2010, patients with hemophilia B received intravenous FIX replacement therapy with standard half-life (SHL) FIX concentrates. To investigate the amount of factor dispensed and the associated medical expenditures for the treatment of hemophilia B in the real-world clinical setting in Japan. This retrospective study comprised patients with hemophilia B (N=197) who had filled prescriptions for FIX concentrates reported in Japan's Medical Data Vision database from 2015 to 2019. Patients were included if they had 2 or more prescriptions for the same FIX concentrates within the first 6 months of the study period and the interval between prescriptions was at least 2 weeks. Since 2015, there was a decrease in the proportion of patients using SHL FIX concentrates and a corresponding increase in international units of dispensed EHL FIX concentrates. Median annualized dispensed dosages (IU/kg body weight) of EHL FIX concentrates were lower than for SHL concentrates for outpatient use only. Annual total health care expenditures per patient and annual expenditures for prescribed FIX concentrates increased each year during the study period. Following a switch from an SHL to an EHL concentrate, the median amount of prescribed FIX concentrate decreased slightly, although median total health care expenditures and FIX concentrate expenditures increased. In the real-world setting in Japan, medical expenditures and the proportion of patients prescribed EHL FIX concentrates for the treatment of hemophilia B have increased.

Abstract 16434: 104-Week Safety and Effectiveness of Low-Density Lipoprotein Cholesterol-Lowering Therapy With Evolocumab in Patients With Familial Hypercholesterolemia/Hypercholesterolemia in Japan: Results of Post-Marketing Surveillance

Introduction: Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia (HC). Aims: This study assessed the 104-week safety and effectiveness of low-density lipoprotein cholesterol (LDL-C)-lowering therapy with evolocumab in patients with FH (homo/heterozygous) and HC in a real-world setting in Japan. Methods: Overall, 3721 and 2792 patients (108 and 91 homozygous FH, 2007 and 1613 heterozygous FH, 1606 and 1088 HC) from 668 clinical sites comprised the safety and effectiveness analysis sets, respectively. Primary safety endpoints: incidence (%) and number of patients with adverse drug reactions and serious adverse events. Effectiveness endpoints: % change in LDL-C from baseline at Week 12 (n=2386, primary endpoint) and Weeks 4-104 (secondary endpoint). Results: Mean age: 63.2 years; female: 33.8%. The mean±SD follow-up duration was 545.5±218.8 days. Adverse drug reaction subject incidence was 5.2%. Serious adverse event subject incidence was 8.9% (330/3721). The adverse event incidences of myocardial infarction and stroke were 0.6% (n=23/3721) and 0.6% (n=21/3721; 0.3% ischemic stroke [n=12]/0.2% hemorrhagic stroke [n=9]), respectively. Table 1 shows adverse events by lowest achieved LDL-C levels. The mean±SD % change in LDL-C from baseline to Weeks 12 and 104 were –45.7%±28.2% (n=84) and –50.9±21.1% (n=48) in homozygous FH patients ( P &lt;0.001 vs baseline; two-sided paired t -test), –56.0%±28.9% (n=1440) and –54.5±28.3% (n=905) in heterozygous FH patients ( P &lt;0.001), and –63.3%±23.7% (n=862) and –60.8±28.1% (n=352) in HC patients ( P &lt;0.001), respectively. Conclusions: There were no trends between the lowest achieved LDL-C levels and adverse events in Japanese patients. Evolocumab was well tolerated and sustained LDL-C reduction in patients with FH and HC in a real-world clinical setting in Japan.

Reduction in asthma exacerbation rate after mepolizumab treatment initiation in patients with severe asthma: A real-world database study in Japan

ObjectiveTo investigate the changes in asthma exacerbation, as well as in oral corticosteroid (OCS) use, exacerbation-related healthcare resource utilization (HRU), and healthcare costs before and after mepolizumab treatment initiation in patients with severe asthma who started treatment with mepolizumab in a real-world clinical setting in Japan. MethodsA retrospective, observational, self-controlled study was conducted in Japan using a hospital-based administrative claims database. Patients who were diagnosed with asthma and who were new users of mepolizumab were included in the study. The primary outcome was the incidence rate of any asthma exacerbation/patient-year during the 12-month period before (baseline period) and after (follow-up period) the first mepolizumab prescription. Secondary outcome measures included the proportion of patients with ≥1 any asthma exacerbation, patients with exacerbation requiring hospitalization, the incidence rate of exacerbations requiring hospitalization/patient-year, the median daily OCS dose (OCS sparing effect), exacerbation-related HRU (hospitalization length, the proportion of patients with emergency visits, and the number of emergency/outpatient visits), and associated costs. ResultsOf the 377 patients included, 56.2% were ≥65 years of age. Following the first mepolizumab prescription, incidence rates for any asthma exacerbation were reduced by 40.6% (4.00/patient-year to 2.38/patient-year; the incidence rate ratio [95% confidence interval]: 0.60 [0.53–0.67]; p < 0.0001) from the baseline to follow-up periods. The incidence rate of exacerbations requiring hospitalization was reduced by 55.8% (0.37/patient-year to 0.16/patient-year) from the baseline to follow-up periods. The proportion of patients experiencing any exacerbation decreased from 84.4% to 57.8% and those requiring hospitalization decreased from 23.9% to 10.3% both from the baseline to follow-up periods. The median daily OCS dose decreased by 44.6% (median [interquartile range]: 6.7 [4.7–9.9] mg/day to 3.3 [0.9–5.6] mg/day) from the last baseline quarter to the 4th quarter of the follow-up period. All exacerbation-related HRUs decreased from the baseline to follow-up periods. Inpatient cost reduced by >50% (123,279 Japanese Yen [JPY]/patient-year vs. 57,283 JPY/patient-year), reducing the total cost by 80,716 JPY from the baseline to follow-up periods. ConclusionMepolizumab was effective in treating patients with severe asthma by reducing the incidence rates of exacerbations and exacerbation requiring hospitalization, OCS dose, exacerbation-related HRU, and cost in routine clinical practice in Japan.

Real-World Treatments and Clinical Outcomes in Advanced NSCLC without Actionable Mutations after Introduction of Immunotherapy in Japan.

Simple SummaryThe aim of this study was to evaluate treatment patterns and real-world clinical outcomes since immunotherapy was introduced in Japan as the initial (first-line) therapy for treating patients with lung cancer, the leading cause of cancer-related deaths in Japan. For 1182 patients with advanced non-small-cell lung cancer, the survival rate at two years after starting first-line therapy was 40% with platinum doublet chemotherapy, 58% with immunotherapy, and 31% with nonplatinum regimens. The results of this large study enabled us to describe the characteristics of a real-world patient population, together with the treatment patterns for advanced non-small-cell lung cancer and clinical outcomes from real-world settings, where most patients receive treatment. Most first-line therapies were administered in accordance with contemporaneous national treatment guidelines, and the study findings indicate improvement in real-world clinical outcomes for patients with advanced non-small-cell lung cancer since the introduction of first-line immunotherapy.The aims of this study were to describe systemic treatment patterns and clinical outcomes for unresectable advanced/metastatic non-small-cell lung cancer (NSCLC) by first-line regimen type in real-world clinical settings in Japan after the introduction of first-line immune checkpoint inhibitor (ICI) monotherapy in 2017. Using retrospective chart review at 23 study sites, we identified patients ≥20 years old initiating first-line systemic therapy from 1 July 2017 to 20 December 2018, for unresectable stage IIIB/C or IV NSCLC; the data cutoff was 30 September 2019. Eligible patients had recorded programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) and no known actionable EGFR/ALK/ROS1/BRAF genomic alteration. Kaplan-Meier method was used to determine time-to-event endpoints. Of 1208 patients, 647 patients (54%) received platinum doublet, 463 (38%) received ICI monotherapy, and 98 (8%) received nonplatinum cytotoxic regimen as first-line therapy. PD-L1 TPS was ≥50%, 1–49% and <1% for 44%, 30%, and 25% of patients, respectively. Most patients with PD-L1 TPS ≥50% received ICI monotherapy (453/529; 86%). Excluding 26 patients with ECOG performance status of 3–4 from outcome analyses, the median patient follow-up was 11.3 months. With first-line platinum doublet, ICI monotherapy, and nonplatinum cytotoxic regimens, median overall survival (OS) was 16.3 months (95% CI, 14.0–20.1 months), not reached, and 14.4 months (95% CI, 10.3–21.2 months), respectively; 24-month OS was 40%, 58%, and 31%, respectively. Differences in OS relative to historical cohort data reported in Japan are consistent with improvement over time in real-world clinical outcomes for advanced NSCLC.

Efficacy of Androgen Receptor-targeted Drugs After Prostate Cancer Recurrence With Bone Metastases: PROSTAT-BSI Sub-analysis.

This study aimed to evaluate the therapeutic benefit of novel androgen receptor-targeted agents (ARTAs) in castration-resistant prostate cancer (CRPC) with bone metastases in Japan. In followup to our prospective observational study (PROSTAT-BSI) from 2012 to 2018 on metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic CRPC (mCRPC) before docetaxel initiation, we conducted this sub-analysis to investigate the benefit of ARTAs after clinical recurrence on overall survival (OS) in the real-world clinical setting in Japan. In this study, we compared patients who were treated with ARTA with those who received only vintage hormone therapy including docetaxel after clinical recurrence. In the mHSPC group, 69 patients became mCRPC and were treated with or without ARTAs. No significant difference was observed in prostate-specific antigen (PSA) progression-free survival between the ARTA (+) and ARTA (-) groups; however, OS after clinical recurrence was significantly better in the ARTA (+) group than in the ARTA (-) group (median OS 31.9 vs. 23.0 months; p<0.01). The ARTAs are beneficial even after mHSPC recurrence in Japanese patients in the real-world clinical setting. Since ARTAs are beneficial after clinical recurrence, it may be better to switch to ARTAs whenever necessary based on PSA response after combined androgen blockade therapy, considering the adverse effects and cost. This approach may be suitable to reduce overtreatment in Japanese patients with mHSPC.

Validation and reliability of current guidelines for the treatment of essential thrombocythemia under real-world clinical settings in Japan

ABSTRACT Objective Current guidelines for essential thrombocythemia (ET) patients recommend different treatment approaches based on thrombosis risk stratification models. However, these recommendations may not be applicable to some patients under real clinical settings. Therefore, we carried out a retrospective real-world validation study. Methods Thrombosis-free survival (TFS) was compared between treatment naïve ET patients receiving different treatment approaches. ET patients were stratified by three representative risk models, the conventional, the International Prognostic Score for thrombosis in ET (IPSET-thrombosis), and revised IPSET-thrombosis. Treatment decisions were largely made by individual physicians, taking into account patient preferences and backgrounds. Results A total of 179 ET patients were included, and thrombotic events were observed in 26 patients. TFS was significantly longer in high-risk patients of all risk models receiving a combination of cytoreductive therapy (CRT) and antiplatelet therapy (APT) compared to CRT alone. Similar results were seen in intermediate-risk patients stratified by IPSET-thrombosis. In contrast, in very low- and low-risk patients of all risk models, TFS was not affected by addition of CRT, indicating that observation or APT alone is an appropriate treatment approach for these patients. Conclusion We demonstrate that current guidelines provide optimal treatment approaches for Japanese ET patients under real-world clinical settings.

1321P Real-world treatments and clinical outcomes in advanced NSCLC without actionable mutations after introduction of immunotherapy (IO) in Japan

IO monotherapies were approved and fully reimbursed for first-line (1L) therapy of unresectable advanced/metastatic NSCLC in February 2017 in Japan. Our aims were to describe treatment patterns and clinical outcomes for advanced NSCLC by regimen type in real-world clinical settings in Japan after the introduction of 1L IO monotherapy.

Efficacy and safety of canakinumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: A single-centre observational study.

To evaluate the efficacy and safety of canakinumab in Japanese patients with colchicine-resistant or colchicine-intolerant familial Mediterranean fever (FMF) in a real-world clinical setting. We reviewed 13 Japanese FMF patients to whom canakinumab was introduced during the period of October 2017 to December 2020. All patients were diagnosed as FMF according to Tel-Hashomer criteria. We performed genetic analyses for Mediterranean fever or MEFV by targeted next-generation sequencing. Efficacy was assessed by attack frequency and the percentage of patients who achieved attack improvement at 24 weeks. Safety was assessed by adverse events observed during canakinumab treatment. The median duration and follow-up of canakinumab treatment were 13 and 16 months, respectively. The median attack frequency was 0.50 [0.30-1.00] at 24 weeks, which was a significant decrease from 2.00 [0.85-2.88] at the time of induction (p = .019). There were three patients (23%) with complete resolution of attacks at 24 weeks. No serious adverse events were observed. However, one patient had small intestinal ulceration which led to the discontinuation of canakinumab. Although the number of cases is small, this study suggests that canakinumab is efficacious and safe for use in Japanese patients with colchicine-resistant or colchicine-intolerant FMF in a real-world clinical setting in Japan.

Real World Treatment Practices for Mantle Cell Lymphoma in Japan: An Observational Database Research Study (CLIMBER-DBR).

Mantle cell lymphoma (MCL) accounts for approximately 3% of all cases of malignant lymphoma in Japan. The CLIMBER-DBR (Treatment practices and patient burden in chronic lymphocytic leukemia and mantle cell lymphoma patients in the real world: An observational database research in Japan) study examined the clinical characteristics, treatment patterns, and healthcare resource utilization of MCL in a real-world clinical setting in Japan. Using the Japanese Medical Data Vision database, we extracted data for 1130 patients with MCL (ICD-10 code C83.1) registered between March 1, 2013 and February 28, 2018. The date of first MCL diagnosis was taken as the index date. The mean (standard deviation) age, body weight, and modified Charlson Comorbidity Index were 71.4 (10.9) years, 58.3 (11.7) kg, and 1.9 (1.6), respectively, and 24.6% were ≤65 years old. The median follow-up period was 654 days (first–third quartile 290.5–1049 days). A total of 802 patients (71.0%) underwent first-line treatment. The most common first-line treatment was bendamustine/rituximab (BR; 27.8%), followed by rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP; 15.6%) and rituximab/tetrahydropyranyl-adriamycin/cyclophosphamide/vincristine/prednisolone (R-THP-COP; 6.5%). The median (95% confidence interval) times to initial (first-line), second-line, and third-line treatments were 45 (36–62), 687 (624–734), and 1188 (1099–1444) days, respectively. Treatment practices for MCL in Japan are consistent with trends observed in Western countries. Our study can serve as a benchmark to assess future MCL treatments in Japan.

Factor analysis of acute kidney injury in patients administered liposomal amphotericin B in a real-world clinical setting in Japan

Liposomal amphotericin B (L-AMB) is a broad-spectrum antifungal drug that is used to treat fungal infections. However, clinical evidence of its use in patients with renal failure is limited. Here, we aimed to identify factors associated with acute kidney injury (AKI) in patients administered L-AMB. We retrospectively utilized a combination of Diagnosis Procedure Combination data and laboratory data obtained from hospitals throughout Japan between April 2008 and January 2018. In total, 507 patients administered L-AMB were identified. After L-AMB treatment initiation, AKI, which was defined as a ≥ 1.5-fold increase within 7 days or ≥ 0.3 mg/dL increase within 2 days in serum creatinine according to the KDIGO criteria, was recognized in 37% of the total patients (189/507). The stages of AKI were stage 1 in 20%, stage 2 in 11%, and stage 3 in 7%. Five factors were associated with AKI of all stages: prior treatment with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers or carbapenem; concomitant administration of catecholamines or immunosuppressants; and ≥ 3.52 mg/kg/day of L-AMB dosing. Serum potassium < 3.5 mEq/L before L-AMB therapy was associated with severe AKI of stage 2 and 3. Altogether, these factors should be carefully considered to reduce the occurrence of AKI in patients administered L-AMB.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Switch rates, time-to-switch, and switch patterns of antiretroviral therapy in people living with human immunodeficiency virus in Japan, in a hospital-claim database

BackgroundRegardless of chronic treatment with antiretroviral therapy (ART), the switching rate for ART regarding anchor drugs has not been articulated in real-world clinical-settings in Japan. We assessed switch rates and time-to-switch of ART regimens according to anchor drug classes (integrase strand transfer inhibitors (INSTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)) and common switching patterns of anchor drug classes in people living with human immunodeficiency virus (HIV) (PLWH) from 2008 to 2016.MethodsThis retrospective, observational study used data of 1694 PLWH drawn from a large-scale medical claims database. The median time-to-switch and switch rates of anchor drug class were estimated by Kaplan-Meier analysis. To estimate 95% confidence intervals for switch rates and median days, the Brookmeyer and Crowley method and Greenwood method were used respectively. The switching patterns were summarized based on the time of switching. The switch rates were compared between two anchor drug classes for each year using log-rank tests.ResultsWe focused our results on 2011–2016 (n = 1613), during which most ART prescriptions were observed. A total of 268 patients switched anchor drug class from the first to a second regimen. The switch rate constantly increased over four years for NNRTIs (17.8–45.2%) and PIs (16.2–47.6%), with median time-to-switch of 1507 and 1567 days, respectively, while INSTI maintained a low switch rate (2.3–7.6%), precluding median-days calculation. The majority originally treated with NNRTI and PI switched to INSTI regardless of the switching timing after starting the first regimen (< 1 year: 91.7 and 97.5%, respectively, and ≥ 1 year: 100.0 and 97.5%, respectively). The risk of switching anchor drug classes was lower for INSTI than for other anchor drug classes in the first regimen even after adjusting for potential confounding factors.ConclusionsPatients with an ART regimen including INSTI as an anchor drug class maintained a low switch rate for long durations. The major switching strategies of anchor drug class for secondary treatment were from NNRTI or PI to INSTI. These results suggest that INSTI may be a durable anchor drug class for PLWH on ART although there are limitations inherent to the database.

Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

IntroductionNatalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis.MethodsDuring the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs).ResultsThe safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing–remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period.ConclusionThe safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation.FundingBiogen Japan Ltd (Tokyo, Japan).

Prasugrel for Japanese patients with acute coronary syndrome in short-term clinical practice (PRASFIT-Practice I): a postmarketing observational study

Data on prasugrel use in Japanese patients are limited to phase II/III clinical trials. This early postmarketing observational study evaluated the safety and efficacy of short-term prasugrel use in patients with acute coronary syndrome (ACS) in real-world clinical settings in Japan. From May 2014 to January 2015, we enrolled consecutive patients with ACS requiring percutaneous coronary intervention in each institution. Each patient started prasugrel treatment ≥1 month before the end of the study period. Safety outcomes included incidence rates of adverse drug reactions (ADRs) and bleeding adverse events (AEs). Efficacy outcomes were incidence rates of cardiovascular events (including major adverse cardiovascular events [MACE]). Case report forms were collected from 749 patients, 732 of whom were eligible for the safety and efficacy analysis sets. Approximately 95% of patients had a prasugrel loading/maintenance dose of 20 mg/3.75 mg/day. The incidences of ADRs and bleeding AEs were 8.6 and 6.4%, respectively. Twelve patients experienced major bleeding AEs; approximately 60% (seven patients) of which were gastrointestinal disorders. The incidence of bleeding AEs was significantly higher primarily in patients of female sex, aged ≥75 years, with low body weight (≤50 kg), severe cardiovascular disease, or severe renal impairment. The incidence of MACE was 1.9% during prasugrel treatment, and 3.1% at the end of the study period. This short-term study indicated that prasugrel treatment at loading/maintenance doses of 20 mg/3.75 mg/day was safe and effective in Japanese ACS patients in an acute setting.Clinical Trial Registration: This study is registered at http://www.umin.ac.jp/ctr/ under the identifier UMIN000014699.

A prospective, multicenter survey on the validity of shorter periendoscopic cessation of antithrombotic agents in Japan.

The management of antithrombotic agents for endoscopic procedures has recently focused on preventing periprocedural thrombosis in Western countries. However, this focus on shorter cessation of antithrombotic agents needs to be examined for its implications for post-procedural bleeding, with potential risk factors for such bleeding clarified in real-world clinical settings in Japan. A Sapporo consensus group convened and developed a consensus document on the criteria for cessation of antithrombotic agents. In the multicenter, prospective, observational study that followed to validate the criteria in a real-world clinical setting, of all patients≥20years of age receiving antithrombotic agents and undergoing endoscopic procedures, all consenting patients were enrolled. All participating facilities were followed up on their adherence to the criteria and clinical outcomes, such as the occurrence of post-procedural bleeding and thrombosis. A total of 5250 patients, who accounted for 6944 endoscopic procedures, were enrolled from 19 study sites. The consensus criteria, which proved to be nearly consistent with the JSGE criteria revised in 2012, had been adhered to in a total of 6531 procedures performed in 4921 patients. Bleeding and thrombosis were reported in 53 (0.76%) and two (0.03%) patients, respectively, among those receiving antithrombotic agents. Post-procedural bleeding was significantly associated with high-bleeding-risk procedures, a high thromboembolic risk with heparin bridging, and the presence of renal failure/dialysis. With the new criteria in place for cessation of antithrombotic agents focused on prevention of periprocedural thrombosis, endoscopic procedures may be safely performed without substantially increasing bleeding in clinical practice in Japan.

Effects of adaptive servo-ventilation therapy on cardiac function and remodeling in patients with chronic heart failure (SAVIOR-C): study protocol for a randomized controlled trial.

BackgroundAdaptive servo-ventilation (ASV) therapy, which is a form of noninvasive positive pressure ventilation therapy and uses an innovative ventilator that has simple operability and provides good patient adherence, potentially has therapeutic benefits—suppression of the deterioration and progression of chronic heart failure (CHF) and a reduction in the number of repeated hospitalizations. Therefore, ASV therapy draws attention as a novel, noninvasive nonpharmacotherapy for patients with CHF owing to its hemodynamics-improving effect, and it is currently being accepted in real-world clinical settings in Japan. However, clinical evidence sufficient for treatment recommendation is lacking because a multicenter, randomized, controlled study of ASV therapy has never been conducted.Methods/DesignThe present study is a confirmatory, prospective, multicenter, collaborative, open-label, blinded-endpoint, parallel-group, randomized, controlled study. At 40 medical institutions in Japan, 200 Japanese outpatients with mild to severe CHF (age: ≥ 20 years; New York Heart Association classification: greater than or equal to class II) will be randomly assigned to either of the following two study groups: the ASV group, in which 100 outpatients undergo guideline-directed medical therapy and ASV therapy for 24 weeks; and the control group, in which 100 outpatients undergo only guideline-directed medical therapy for 24 weeks. The objective of the present study is to confirm whether the ASV group is superior to the control group concerning the improvement of left ventricular contractility and remodeling, both assessed by two-dimensional echocardiography. Furthermore, the present study will also secondarily examine the effects of ASV therapy on the prognosis and quality of life of patients with CHF.DiscussionASV therapy using the device has the potential to provide therapeutic benefits based on its simple operability and good patient adherence and possesses the potential to improve left ventricular contractility and remodeling. Therefore, the present study is expected to afford more solid scientific evidence regarding ASV therapy as a novel, noninvasive, nonpharmacological, in-home, long-term ventilation therapy for patients with mild to severe CHF.Trial registrationUMIN identifier: UMIN000006549, registered on 17 October, 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-014-0530-z) contains supplementary material, which is available to authorized users.

Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan

An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan. Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness. A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score-erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously. These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.

SAT0120 Characteristics Associated with Better Effectiveness and Safety in Rheumatoid Arthritis Patients Treated with Intravenous Tocilizumab: Results from Full Analysis of All-Patient Postmarketing Surveillance in Japan

ObjectivesThis all-patient postmarketing surveillance aimed to evaluate the safety and effectiveness of tocilizumab (TCZ) for RA in the real-world clinical setting in Japan.MethodsPatients received 8 mg/kg TCZ every 4 weeks...