Clinical Practice In Japanese Patients Research Articles

Effect of Baseline Values of Renal Prognosis-related Factors on Their Changes after Initiating Tofogliflozin Treatment: A Retrospective Study in Japanese Patients with Type 2 Diabetes and Renal Impairment.

This study investigated the relationships between changes in renal prognosis-related factors after initiating tofogliflozin and the corresponding baseline values in clinical practice in Japanese patients with type 2 diabetes. We investigated the relationships between changes in hematocrit, hemoglobin, systolic blood pressure (sBP), urinary protein excretion (uPE), serum uric acid (sUA), and estimated glomerular filtration rate (eGFR) 12 months after initiating tofogliflozin (20 mg) and their corresponding baseline values in 130 patients with type 2 diabetes. The subjects were divided into two groups: normal (≥60 mL/min/1.73 m2, n = 87) and low (<60 mL/min/1.73 m2, n = 43) eGFR. Although the change in eGFR was negatively correlated with the baseline value in the normal-eGFR group, no significant correlation was found between the change in eGFR and baseline value in the low-eGFR group. Although changes in hematocrit (r = -0.39, P = 0.01) and hemoglobin (r = -0.36, P = 0.02) levels were significantly negatively correlated with corresponding baseline values in the low-eGFR group, no significant correlations were observed in the normal-eGFR group. Changes in sBP, uPE, and sUA were significantly negatively correlated with the corresponding baseline values in both the normal- and low-eGFR groups. None of the correlation coefficients between the normal- and low-eGFR groups showed a significant difference. Favorable changes in renal prognosis-related factors after tofogliflozin therapy may contribute to renoprotection in patients with type 2 diabetes and poor corresponding baseline values, despite the presence of renal impairment.

Utility of the Dermatology Life Quality Index at initiation or switching of biologics in real-life Japanese patients with plaque psoriasis: Results from the ProLOGUE study

BackgroundPlaque psoriasis significantly affects patients’ health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important. ObjectiveTo assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis. MethodsThis was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). ResultsOf the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5. ConclusionDLQI may be useful for assessing patients’ concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.

Safety and effectiveness of adalimumab in the treatment of ulcerative colitis: results from a large-scale, prospective, multicenter, observational study.

Background/AimsAdalimumab has been shown to induce and maintain clinical remission in patients with moderate to severe ulcerative colitis (UC). However, no large-scale population-based studies have been performed in Japan. This study was conducted to evaluate the safety and effectiveness of adalimumab in clinical practice in Japanese patients with UC.MethodsIn this 52-week, prospective, multicenter, single-cohort, noninterventional, observational, postmarketing surveillance study, patients with moderate to severe UC received an initial subcutaneous injection of adalimumab 160 mg, followed by 80 mg at 2 weeks, and then 40 mg every other week. Safety assessments were the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness assessments were clinical remission, corticosteroid-free remission, mucosal healing, and change in C-reactive protein (CRP) levels from baseline.ResultsOf 1,593 registered patients, 1,523 (male, 57.6%; mean age, 41.8 years) and 1,241 patients were included in the safety and effectiveness populations, respectively. ADRs were reported in 18.1% and serious ADRs in 4.9% of patients. Clinical remission was achieved in 49.7% of patients at week 4, increasing to 74.4% at week 52. Corticosteroid-free remission rates increased over time, from 10.4% at week 4 to 53.1% at week 52. More than 60% of patients demonstrated mucosal healing at weeks 24 and 52. Mean CRP levels (mg/dL) decreased from 1.2 at baseline to 0.6 at week 4 and 0.3 at week 52.ConclusionsThis large real-world study confirmed the safety and effectiveness of adalimumab in patients with UC in Japan. No new safety concerns were identified.

Treatment satisfaction, safety, and effectiveness of biosimilar insulin glargine is comparable in patients with type 2 diabetes mellitus after switching from insulin glargine or insulin degludec: a post-marketing safety study

Objective To evaluate insulin treatment satisfaction, safety, and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice for Japanese patients with type 2 diabetes mellitus (T2DM) who switched from originator insulin glargine (100 U/mL) or insulin degludec treatment to GLY treatment. Methods The Insulin Treatment Satisfaction Questionnaire (ITSQ) was used to assess treatment satisfaction in a subgroup analysis of a post-marketing safety study. Hypoglycemia incidence rates and blood glucose control are also reported during the 12-month observation period for GLY-switched patients. Results Of 1104 patients with T2DM enrolled to participate, 565 patients switched from either insulin glargine U100/mL (n = 470) or insulin degludec (n = 95) to GLY. The mean total change from baseline to 3 months for total ITSQ score was 1.35 (95% confidence interval [CI] − 0.13 to 2.83, p = .073) for patients who switched from insulin glargine and 2.63 (95% CI −1.43 to 6.70, p = .195) for patients who switched from insulin degludec to GLY treatment. The mean change from baseline to 12 months in hypoglycemia events reported per month was −0.04% (95% CI −0.12 to 0.03, p = .236) for patients who switched from insulin glargine and no change for patients who switched from insulin degludec (0.00, 95% CI −0.20 to 0.20, p = 1.000). Non-significant mean changes from baseline to 12 months were observed for hemoglobin A1c and fasting plasma glucose in GLY-switched patients. Conclusions Treatment satisfaction does not change significantly in Japanese patients with T2DM who switch to GLY from the reference product or from insulin degludec. Safety and effectiveness over a 12-month period were similar in GLY-treated patients who switched from either insulin glargine or insulin degludec. ClinicalTrials.gov Not applicable.

Real-World Evidence for Long-Term Safety and Effectiveness of Ipragliflozin in Japanese Patients with Type 2 Diabetes Mellitus: final Results of a 3-Year Post-Marketing Surveillance Study (STELLA-LONG TERM)

ABSTRACT Objective To evaluate the long-term safety and effectiveness of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes mellitus (T2DM). Research design and methods This post-marketing surveillance study (STELLA-LONG TERM) included Japanese patients newly initiated on ipragliflozin between 17 July 2014 and 16 October 2015 (data lock: 30 September 2019). Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. Results Of 11,424 registered patients, safety and efficacy analysis sets comprised of 11,051 and 8,763 patients, respectively. ADRs occurred in 2,129 patients (19.27%) and serious ADRs occurred in 210 patients (1.90%). Renal and urinary disorders (n = 739, 6.69%), particularly polyuria/pollakiuria (n = 612, 5.54%) and volume depletion-events, including dehydration (n = 243, 2.20%), comprised the most common ADRs. Mean (SD) change in hemoglobin A1c (─0.66 [1.25] %), fasting plasma glucose (─28.8 [50.1] mg/dL) and body weight (─3.33 [4.32] kg) from baseline to 36 months were statistically significant (P < 0.001). Conclusions The safety profile of long-term ipragliflozin treatment in routine clinical practice is consistent with previously reported interim data at 12 or 24 months and pre-approval clinical trials. Ipragliflozin treatment was also associated with sustained improvements in efficacy parameters for over 3 years.

Effect of liraglutide on lipids in patients with type 2 diabetes: a pilot study.

The mechanism for the cholesterol-lowering effect of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown in patients with type 2 diabetes. We evaluated the effect of liraglutide on serum lipid profiles, including cholesterol synthesis and absorption markers, during daily clinical practice in Japanese patients with type 2 diabetes. We enrolled 38 patients with type 2 diabetes mellitus who were not treated with a GLP-1 RA (≥20 years of age, HbA1c ≥6.5%). Liraglutide, a GLP-1 RA, was administered subcutaneously once a day for three months to these patients. Blood samples and body weights were collected at 0, 1, and 3 months. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) at 1 month, and non-high-density lipoprotein cholesterol (non-HDL-C) and calculated TC at 1 and 3 months, were decreased, while the cholesterol synthesis and cholesterol absorption markers were unchanged by this treatment. In patients with LDL-C levels over 100 mg/dL, LDL-C, non-HDL-C, TC, and calculated TC levels were decreased significantly by the treatment at 1 and 3 months, and the cholesterol absorption marker, campesterol, was decreased at 3 months. The administration of liraglutide for 3 months decreased non-HDL-C and calculated TC significantly, while the cholesterol synthesis and absorption markers were not changed by this treatment.

A multicenter retrospective study of Paclitaxel vs. Paclitaxel plus Ramucirumab for advanced gastric cancer patients

Abstract Background Ramucirumab (RAM) conferred survival benefit in patients with advanced gastric cancer (AGC) in the RAINBOW trial (HR 0.807, 95% CI: 0.678-0.962, p = 0.017). However, in the Japanese subpopulation, adding RAM showed modest overall survival (OS) benefit compared with patients in Western country (HR 0.88 vs. 0.73). The objective of this retrospective study was to clarify additional benefit of RAM in clinical practice for Japanese patients. Method We reviewed medical records of AGC patients who were treated with Paclitaxel (PTX) or PTX+RAM between Jan 2014 and Dec 2016 as second-line treatment in 9 Japanese institutions, excluding patients with prior use of taxane or RAM. Result A total of 154 patients were included (63 in PTX and 91 in PTX+RAM). Patient characteristics of PTX vs. PTX+RAM groups were: age (median) 64 vs. 64, male 67% vs. 75%, PS (0/1/2) 27/63/10% vs. 30/67/3%, disease status (metastatic/recurrent) 75/25% vs. 63/37%, histology (intestinal/diffuse/other) 24/57/19% vs. 31/44/25%, number of metastatic sites (0-2/≥3) 75/25% vs. 70/30%, ascites (+/-) 54/46% vs. 50/50%, and platinum combined with fluoropyrimidine in the first line (oxaliplatin/cisplatin) 16/84% vs. 37/63%. The median OS in the PTX vs. PTX+RAM groups were 7.0 vs. 9.3 months (HR 0.73, 95% CI: 0.52-1.04, p = 0.083). The median PFS were 3.2 vs. 4.1 months (HR 0.66, 95% CI: 0.47-0.93, p = 0.016). Among 39/55 patients who had measurable lesions, response rate and disease control rate were 18% vs. 35% and 56% vs. 76%, respectively. The proportion of patients receiving subsequent treatment was 57% in PTX group and 59% in PTX+RAM group. Grade 3 or more adverse events were observed more frequently in PTX+RAM group, including neutropenia (55% vs. 21%) and leucopenia (31% vs. 19%) than PTX group. Conclusion Although this study was retrospective investigation with small sample size, adding RAM to PTX conferred clinically meaningful efficacy and safety in clinical practice for Japanese patients.

Effectiveness and safety of long-term dabigatran among patients with non-valvular atrial fibrillation in clinical practice: J-dabigatran surveillance

BackgroundThe effectiveness and safety of dabigatran etexilate (DE) have not been elucidated thoroughly in clinical practice for Japanese patients with non-valvular atrial fibrillation (NVAF). In particular, those of DE at a reduced dose due to dose reduction recommendations (DRR) remain unknown. MethodsNVAF patients who had newly initiated DE treatment for prevention of thromboembolic events between December 2011 and November 2013 were enrolled. They were followed until August 2016. Outcome events included thromboembolism, major bleeding, and all-cause death. ResultsThe study group consisted of 6443 patients (mean age, 70.9 years; male, 66.9%; and mean CHADS2 score, 1.8). During a follow-up period of 610 days (median), stroke, transient ischemic attack (TIA), and systemic embolism (SE) occurred at 1.4%/year for DE 110mg twice daily (BID) (DE220, n=4759) and 0.8% for dabigatran 150mg BID (DE300, n=1571, unadjusted p=0.0317). Major bleeding occurred at 1.3 and 0.6%/year for DE220 and DE300, respectively (unadjusted p=0.0097). All-cause death occurred at 1.5 and 0.5%/year for DE220 and DE300, respectively (unadjusted p=0.0005). When patients were divided into four groups based on DRR and DE doses (DE300 groups meeting and not meeting DRR, and DE220 groups meeting and not meeting DRR), incidence rates of stroke/TIA/SE and major bleeding differed among the four groups (unadjusted p=0.0026 and 0.0194 for trend, respectively); DE220 group meeting DRR had the highest rates (1.7% and 1.4%/year, respectively). However, in multivariate analysis, no differences between doses were observed regarding any outcomes. ConclusionsThe present results are indicative of the favorable benefit-risk profile of dabigatran in Japanese clinical practice. Dabigatran dose was not independently associated with thromboembolic and bleeding events in Japanese NVAF patients.

Safety and effectiveness of daclatasvir and asunaprevir dual therapy in patients with genotype 1 chronic hepatitis C: results from postmarketing surveillance in Japan.

Safety and effectiveness of daclatasvir (DCV)/asunaprevir (ASV) dual therapy were demonstrated in Japanese patients with chronic hepatitis C (CHC) genotype (GT) 1b in phase III studies. This postmarketing surveillance (PMS) was conducted to assess the safety and effectiveness of DCV/ASV in Japanese patients with GT-1 CHC treated in routine clinical practice. This PMS was conducted between September 2014 and February 2017 at 261 centers in Japan. Patients with GT-1 CHC with or without compensated cirrhosis starting DCV and ASV dual therapy were observed from treatment initiation until 24weeks after completing treatment. Safety and effectiveness assessments included incidence of adverse drug reactions (ADRs) and sustained viral response (SVR) rates at 24weeks (SVR24). Of 2820 patients (median age, 71.0years; ≥ 65years, 73.1%; female, 56.1%; with compensated cirrhosis, 39.1%) in the safety population, 726 (25.7%) experienced 1063 ADRs and 47 (1.7%) experienced 55 serious ADRs. Overall, 532 hepatic ADRs were reported; most hepatic ADRs occurred between > 4 and ≤ 12weeks after treatment initiation. Subgroup analysis showed a higher incidence of ADRs in female, elderly, underweight, and renal function-impaired patients. SVR24 and SVR at 12weeks (SVR12) were 87.3% (2216/2538) and 88.4% (2284/2584), respectively. Patients without (SVR12, 89.1%; SVR24, 87.9%) and with (SVR12, 87.3%; SVR24, 86.3%) compensated cirrhosis had similar SVR rates. Results from this large PMS indicate that DCV and ASV dual therapy is generally well tolerated and effective in routine clinical practice in Japanese patients with GT-1 CHC with or without compensated cirrhosis.

P3.02b-097 Experience of Re-Biopsy (Biopsy at Progression) of EGFR Mutant Non-Small Cell Lung Cancer Patients in Japan: A Retrospective Study: Topic: EGFR RES

To confirm mechanisms of resistance to targeted therapy and to evaluate future treatment strategy, biopsy at progression is important and necessary. Since biopsy at progression is not standard of care, we investigated real-world clinical practice in Japanese patients with non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) gene mutation. This was a retrospective, multi-center, observational study in Japan. EGFR mutation positive NSCLC patients who developed disease progression after treatment by EGFR tyrosine kinase inhibitor were enrolled. The primary objective was the success rate of re-biopsy (biopsy at progression). The secondary objectives were differences of between the first biopsy and re-biopsy (e.g. sampling method, target organ of biopsy) and complications associated with re-biopsy. 395 patients were evaluated, median age was 63 years, and the most common histological type was adenocarcinoma (96.2%). Success rate of re-biopsy was 79.5% (314/395) of patients. Compared with the first biopsy, surgical biopsy increased from 1.8% to 7.8%, percutaneous tissue biopsy increased from 7.6% to 29.1%. Most commonly performed gene mutation tests using specimen collected by re-biopsy were EGFR (94.3%), EML4-ALK (22.0%) and KRAS (14.3%). T790M mutation was detected in 147 (49.7%) out of 296 patients. 23 patients (5.8%) had complications associated with re-biopsy, the most common complication was pneumothorax. A repeated re-biopsy was successful in 87.5% (28/32) of patients.TableRe-biopsy success rate by site and sampling methodNo. of patientsSuccess rate (%)By SitePrimary site220168 (76.4%)Metastatic site121103 (85.1%)Lymphnodes5040 (80.0%)Others43 (75.0%)By sampling methodTransbronchial biopsy; forceps204147 (72.1%)Transbronchial biopsy; needle4134 (82.9%)Percutaneous needle biopsy under CT guidance7766 (85.7%)Percutaneous needle biopsy under ultrasonic guidance3634 (94.4%) Open table in a new tab The observed success rate of re-biopsy was approximately 80% in this study. T790M detection rate was comparable to the previously reported studies. Re-biopsy for the EGFR TKI failure NSCLC patients is feasible in Japan.

Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice

ABSTRACTObjective: To evaluate the efficacy and safety of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes.Research design and methods: We conducted interim analyses at 3 months of a 3-year prospective study of patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015, and whose data were locked by 16 January 2016.Main outcome measures: Changes in glycemic control, blood pressure, and laboratory variables from baseline, and incidence of adverse drug reactions (ADRs).Results: Of 11,412 patients initially registered, efficacy and safety data were available for 3481 (30.5%) and 4360 (38.2%) patients, respectively. Hemoglobin A1c and fasting plasma glucose decreased by 0.67% and 28.8 mg/dL, respectively, at 3 months/last assessment (both P < .001) from baseline (8.00% and 166.4 mg/dL, respectively). Blood pressure and lipid levels also improved significantly. There were 258 ADRs in 194 patients. The ADRs included ‘renal and urinary disorders’ (system organ class) in 110 patients (2.5%).Conclusions: These 3-month interim results indicate that ipragliflozin improved glycemic control, lipids, and blood pressure with low rates of ADRs in Japanese patients with type 2 diabetes in real-world clinical practice. The results were consistent with those of placebo-controlled, randomized clinical trials.Clinicaltrials.gov identifier: NCT02479399

Efficacy and safety of novel anticoagulant dabigatran in clinical practice for Japanese patients with non-valvular atrial fibrillation

BackgroundThere is little evidence of the efficacy and safety of dabigatran in Japanese patients with non-valvular atrial fibrillation (NVAF). Methods and ResultsWe evaluated 300 consecutive patients with NVAF (68±11 years old, 209 men, 180 paroxysmal) who received 220mg/day (203 patients) or 300mg/day dabigatran (97 patients) at our hospital. Most patients (84%) had lower CHADS2 (congestive heart failure, hypertension, age>75 years, diabetes, stroke/transient ischemic attack) scores of 0 (n=60), 1 (n=114), or 2 (n=78) and lower HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition) scores of 0 (n=39), 1 (n=114), or 2 (n=103). The estimated creatinine clearance was 77±24mL/min, which was inversely correlated to age (r2=0.48, p<0.0001). Activated partial thromboplastin time was 42±9 s but was not dependent on sampling time. During follow-up of 263±160 days, an ischemic stroke occurred in 1 patient (0.3%), but no systemic embolism was observed. Some adverse events were reported for 70 (23%) patients, such as dyspepsia (n=42, 14%) or minor bleeding complications (n=11, 4%) resulting in discontinuation of dabigatran for 39 patients. However, no major complications were observed, and no patient died from adverse events or because of cardiovascular or stroke events. ConclusionsDabigatran is safe and useful for the prevention of ischemic strokes in Japanese NVAF patients, but additional care should be taken for elderly patients.

Effectiveness of Golimumab in Clinical Management of Patients with Rheumatoid Arthritis

Background and ObjectivesLimited data are available regarding the use of golimumab (100 mg) every 4 weeks, with or without methotrexate (MTX). The aim of this retrospective analysis was to evaluate the effectiveness and safety of golimumab following usual clinical practice in Japanese patients with rheumatoid arthritis (RA) according to the recommendations given in the Japanese package insert.Patients and MethodsJapanese RA patients with moderate-to-high disease activity, according to the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) criteria, despite treatment with MTX or another biological agent, were enrolled. Patients were assigned to 50 mg golimumab plus MTX or 100 mg golimumab monotherapy every 4 weeks for 24 weeks. All patients were given MTX if it was not contraindicated. The primary endpoint was the proportion of patients achieving clinical remission (defined as a DAS28-CRP <2.3 or a simplified disease activity index [SDAI] score <3.3) at 24 weeks.ResultsMost patients received combined 50 mg golimumab plus MTX (41/43). In these patients, the primary endpoint, clinical remission, was attained in 83 % of patients according to DAS28-CRP criteria (p < 0.001) and 69 % according to SDAI criteria (p < 0.001) by week 24. Adverse events were reported in 11.6 % of patients receiving golimumab.ConclusionsGolimumab (50 mg) plus MTX effectively reduced the signs and symptoms of RA and was generally well tolerated in patients with an inadequate response to MTX and other biological agents.