Long-Term Safety and Efficacy of Teneligliptin in Elderly Patients with Type 2 Diabetes: Subgroup Analysis of a 3-Year Post-Marketing Surveillance in Japan.
Ontology highlight
ABSTRACT:
SUBMITTER: Kadowaki T
PROVIDER: S-EPMC7467469 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
Long-Term Safety and Efficacy of Teneligliptin in Elderly Patients with Type 2 Diabetes: Subgroup Analysis of a 3-Year Post-Marketing Surveillance in Japan.
Kadowaki Takashi T Haneda Masakazu M Ito Hiroshi H Sasaki Kazuyo K Yamada Yuka Y
Advances in therapy 20200422 5
<h4>Introduction</h4>Teneligliptin, a dipeptidyl peptidase 4 inhibitor, was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. However, clinical trials of teneligliptin involved limited numbers of elderly patients. Therefore, we investigated the safety and efficacy of teneligliptin in elderly patients with T2DM.<h4>Methods</h4>This 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2 ...[more]
Similar Datasets
Project description:IntroductionTeneligliptin is a dipeptidyl peptidase 4 inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. We performed a long-term post-marketing surveillance (RUBY) to obtain real-world evidence regarding the safety and efficacy of teneligliptin in Japan.MethodsThis 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2015 in Japan. Collected data included demographics, treatments, adverse drug reactions (ADRs) and laboratory variables. Data were evaluated in all patients and in patients divided according to baseline renal function across categories of estimated glomerular filtration rate (G1-G5) and dialysis. Safety was assessed as the incidence of ADRs and efficacy was assessed in terms of glycaemic control, for up to 3 years.ResultsOf 11,677 patients registered, 10,696 and 10,249 were evaluable for safety and efficacy analyses, respectively. The median duration of exposure was 1096 days. ADRs occurred in 412 patients (3.85%) and were serious in 117 patients (1.09%). The most frequent ADR class was gastrointestinal disorders (0.68%), which included constipation. There were no new ADRs warranting attention beyond those already described in teneligliptin's package insert. ADRs and serious ADRs in renal function subgroups occurred in 3.24-7.14% and 0.65-5.36% in G1-G5, and 4.49% and 1.92% in patients on dialysis, respectively. Reduction in HbA1c was sustained for 3 years after starting teneligliptin (- 0.70% ± 1.36%, p < 0.001 at 3 years). The least-squares mean changes in HbA1c adjusted for baseline were - 0.76% to - 0.66% in G1-G5 at 3 years. Glycated albumin levels decreased in patients on dialysis (- 2.92% ± 4.78% at 3 years).ConclusionThere were no new safety or efficacy concerns about teneligliptin used in long-term, real-world, clinical settings in patients with T2DM with any stages of renal impairment.Trial registrationJapan Pharmaceutical Information Center clinical trials database identifier: Japic CTI-153047. Plain language summary available for this article.
| S-EPMC7089720 | biostudies-literature
Project description:BackgroundGaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering type 1, 2 or 3 GD. METHODS: All patients with type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed. RESULTS: In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with type 2 GD. ADRs were reported by 63.6% (7/11) of patients with type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results. CONCLUSION: PMS data from patients with types 1-3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan.Trial registrationNCT03625882 registered July 2014.
| S-EPMC8642863 | biostudies-literature
Project description:Background and aimUstekinumab, a human anti-interleukin-12/23 monoclonal antibody, has been approved in Japan for the treatment of Crohn's disease. Here, we report the findings from an 8-week interim analysis of post-marketing surveillance to evaluate the safety and effectiveness of ustekinumab in Japanese patients with Crohn's disease.MethodsPatients initiating ustekinumab treatment were prospectively evaluated from May 2017 to June 2020 at 91 medical centers in Japan. Adverse drug reactions (ADRs) and serious ADRs (SADRs) were monitored. Effectiveness was evaluated by clinical response, clinical remission, and changes in Crohn's Disease Activity Index (CDAI) and C-reactive protein (CRP) from baseline to week 8. Presence of perianal disease was documented at baseline and week 8.ResultsIn total, 341 patients were enrolled in the study, of which 339 were included in the safety analysis while 334 were included in the effectiveness analysis. The overall incidences of ADRs and SADRs were 5.3% and 2.1%, respectively. Worsening of Crohn's disease was the most common event. The clinical response and clinical remission rate at week 8 were 40.0% and 48.5%, respectively. Significant improvements in CDAI and serum CRP (P < 0.001) were observed at week 8. CDAI decreased significantly (mean difference: -31.4; 95% confidence interval: -61.1, -1.7; P = 0.038) in biologics-naïve patients versus patients who had received two or more biologics.ConclusionsThis 8-week interim analysis of the real-world study confirmed the effectiveness of ustekinumab-based therapy in Japanese patients with Crohn's disease. No new safety concerns were found during 8-week induction period in the Japanese clinical settings.
| S-EPMC9290907 | biostudies-literature
Project description:STELLA-LONG TERM, a 3-year post-marketing surveillance study, evaluated the safety and effectiveness of the sodium-glucose cotransporter 2 inhibitor ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients. Final results in the safety (n = 6697) and effectiveness populations (n = 5625) were analyzed by stratifying patients by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) into four subgroups (≥ 90, 60 to < 90, 45 to < 60, and < 45) and two subgroups (≥ 60 and < 60). Adverse drug reaction (ADR) incidence, and changes from baseline in glycosylated hemoglobin (HbA1c), bodyweight, and eGFR were assessed. The percentage of patients experiencing ADRs and serious ADRs was similar across most eGFR subgroups. Polyuria/pollakiuria was the most common ADR. Renal disorders and volume depletion ADRs were more frequent in the subgroups with more severe renal impairment at baseline than in those with an eGFR of 60 to < 90 or ≥ 90 mL/min/1.73 m2. Bodyweight and HbA1c decreased in all subgroups, the latter by - 0.91% to - 0.40% (P < 0.05 vs. baseline). eGFR increased in the 45 to < 60 mL/min/1.73 m2 subgroup (+ 1.42 ± 8.77 mL/min/1.73 m2; P = 0.006). It decreased in the ≥ 90 and 60 to < 90 mL/min/1.73 m2 subgroups (- 8.27 ± 13.73 and - 1.22 ± 10.34 mL/min/1.73 m2; P < 0.001), but not to < 60 mL/min/1.73 m2. In conclusion, there were no new or unexpected safety findings in Japanese patients treated with ipragliflozin for T2DM, and long-term sustained improvements in HbA1c and bodyweight were observed regardless of the presence of renal impairment.
| S-EPMC7943685 | biostudies-literature
Project description:INTRODUCTION:Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. METHODS:For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. RESULTS:A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. CONCLUSIONS:During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from normal to end-stage renal disease, including those on dialysis, and improved glycemic control. TRIAL REGISTRATION NUMBER:Japic CTI-153047. FUNDING:Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.
| S-EPMC5984919 | biostudies-literature
Project description:BackgroundTo understand the extent to which a large-scale healthcare claims database (DB) captures the safety profile of eribulin mesylate (Halaven®, Eisai Co., Ltd., Japan), we compared patient characteristics, drug use, and adverse events (AEs) between data for patients treated with eribulin retrieved from a DB and data for metastatic breast cancer patients from a conventional prospective post-marketing surveillance (PMS).MethodsWe descriptively summarized patient characteristics and AEs of 551 and 951 patients retrieved from DB and PMS, respectively, during 2011‒2013. Using 2814 patient data from the DB during 2011‒2016, the drug use and AE incidence over time were assessed.ResultsIn both datasets, 99.8% were females, and the mean age was 57.8 ± 10.7 years. The mean number of eribulin administration was 11.1 ± 10.9 and 10.1 ± 7.8 in DB and PMS, respectively. Although, overall, the difference in AE incidence between the two datasets was moderate, gaps were larger for nausea (DB: 73.32% vs. PMS: 15.77%), neutropenia (20.87% vs. 66.67%), stomatitis (37.39% vs. 10.94%), and alopecia (0.36% vs. 12.09%). During 2011‒2016, the observed incidence of anemia or pyrexia significantly decreased (trend test, p = 0.0009 for both).ConclusionGenerally, patient characteristics, drug use, and AE incidence between the DB and PMS were comparable; however, AEs such as neutropenia may require defining based on the laboratory data to achieve more comparable results in DBs. Besides the usefulness of healthcare claims DBs for long-term assessments, they may also serve as a good complementary to PMS in the pharmacovigilance of eribulin.
| S-EPMC6423272 | biostudies-literature
Project description:INTRODUCTION:Clinical trials of linagliptin in Japanese patients conducted to date have had limited observational periods; therefore, there is a need for additional longer-term real-world data. The aim of this study was to investigate the long-term safety and effectiveness of linagliptin in routine clinical practice. METHODS:This was a prospective, observational, post-marketing surveillance study conducted over 156 weeks in patients with type 2 diabetes mellitus who started linagliptin monotherapy. The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to last available observation. Other effectiveness endpoints included the change in HbA1c and change in fasting plasma glucose (FPG) from baseline to week 26 and over the course of the treatment period. RESULTS:Overall, 2235 and 2054 patients were included in the safety and effectiveness analysis sets, respectively. Patients were mostly male (58.4%), and the mean age was 66.7 years. The incidence of ADRs was 10.7% (n = 240). The most frequent ADRs according to MedDRA preferred terms were diabetes mellitus (n = 35 patients, 1.6%), constipation (n = 21, 0.9%), diabetes mellitus inadequate control (n = 13, 0.6%) and hypertension (n = 13, 0.6%). The mean change in HbA1c from baseline to last observation was - 0.67% [standard deviation (SD) 1.27%, 95% confidence interval - 0.72, - 0.61]. At week 26, HbA1c and FPG showed mean ± SD changes from baseline of - 0.73 ± 1.20% and - 21.02 ± 44.33 mg/dL, respectively, that were sustained until week 156. CONCLUSIONS:In Japanese patients with type 2 diabetes mellitus, linagliptin produced sustained reductions in HbA1c and had a safety profile consistent with the established safety profile of linagliptin. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01650259).
| S-EPMC6965601 | biostudies-literature
Project description:BackgroundNo data on the long-term 'real-world' use of fluvoxamine for the treatment of social anxiety disorder (SAD) in Japanese patients are currently available.ObjectiveTo evaluate the long-term safety and efficacy of fluvoxamine for SAD in the clinical setting.MethodsJapanese patients with SAD who initiated treatment with fluvoxamine were enrolled in this 53-week post-marketing survey from 407 institutions nationwide. Data including rates of adverse drug reactions (ADRs) and efficacy were collected. Overall improvement was assessed using the Clinical Global Impression for Improvement. SAD symptoms and treatment responses were assessed with the Japanese version of the Liebowitz Social Anxiety Scale.ResultsFrom the 1,974 patients surveyed, 1,790 and 1,504 patients were eligible for analysis of safety and efficacy, respectively. ADRs were reported in 18.2 % of patients, with nausea, somnolence, and constipation the most common. Over 50 % of these ADRs developed in the first 4 weeks of treatment. Serious ADRs were reported in 0.8 % of patients and included six cases of suicide attempt and three cases of suicidal ideation. Response to fluvoxamine was reported in 78.4 % of patients. In patients comorbid with depression, improvement in SAD symptoms with fluvoxamine treatment was significantly affected by clinical improvement in the depression.ConclusionsThese findings support the long-term safety and efficacy of fluvoxamine in patients with SAD. Most ADRs developed during the early treatment phase, and higher doses during the later phase were not associated with an increase in ADRs.
| S-EPMC4883186 | biostudies-literature
Project description:IntroductionThe present interim report of the STELLA-LONG TERM study aimed to examine the safety and effectiveness of ipragliflozin in real-word clinical practice in Japan using data up to 12 months. We also evaluated the effect of ipragliflozin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with normal vs. abnormal liver function.MethodsThis is an ongoing 3-year post-marketing surveillance study. We analyzed data from Japanese type 2 diabetes mellitus (T2DM) patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan, and whose data were locked by 16 January 2018. The incidence of adverse drug reactions (ADRs) was evaluated for safety. Changes in glycemic control and body weight were evaluated for effectiveness. The effect on liver function was evaluated by changes in the fatty liver index, and changes in AST and ALT were evaluated in patients with normal and abnormal liver function.ResultsThe safety analysis set comprised 11,051 patients and the efficacy analysis set comprised 8788 patients. The incidence rates of ADRs and serious ADRs were 14.6% (1616/11,051) and 0.97% (107/11,051), respectively. Significant reductions (all P < 0.001 vs. baseline, paired t test) in glycated hemoglobin (- 0.8%), fasting plasma glucose (- 31.9 mg/dL), body weight (- 2.9 kg), and fatty liver index (- 8.7) were observed. In patients with normal liver function at baseline, no clinically significant changes in AST and ALT were observed. In patients with abnormal liver function at baseline, clinically and statistically significant decreases (P < 0.05 vs. baseline, two-sample t test) in AST (- 9.0 U/L) and ALT (- 14.7 U/L) levels were observed.ConclusionIpragliflozin was effective and well tolerated in Japanese patients with T2DM over 12 months in the real-world clinical setting. Improvements in liver function parameters (AST and ALT) were observed in T2DM patients with abnormal liver function.Trial registrationClinicalTrials.gov identifier, NCT02479399.FundingAstellas Pharma Inc., Japan.
| S-EPMC6824450 | biostudies-literature
Project description:IntroductionThis long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to patients with type 2 diabetes mellitus (T2DM) in real-world practice in Japan.MethodsPatients with T2DM who were prescribed canagliflozin between December 2014 and September 2016 were registered and observed for up to 3 years. Safety was evaluated in terms of adverse drug reactions (ADRs). Effectiveness was assessed in terms of glycaemic control. Data were also analysed across age subgroups (< 65, ≥ 65 to < 75, and ≥ 75 years old) and the estimated glomerular filtration rate (eGFR) categories for chronic kidney disease (G1-G5 based on eGFR) at baseline.ResultsA total of 12,227 patients were included in the safety analyses and 11,675 in effectiveness analyses. Overall, 7104 patients were treated with canagliflozin for ≥ 3 years. The mean age, haemoglobin A1c (HbA1c), and eGFR at baseline were 58.4 ± 12.5 years, 8.01 ± 1.49%, and 80.04 ± 21.85 mL/min/1.73 m2, respectively. There were 1836 ADRs in 1312 patients (10.73%) and 268 serious ADRs in 225 patients (1.84%). The most common ADRs were those related to volume depletion (1.39%), genital infection (1.34%), polyuria/pollakiuria (1.23%), and urinary tract infection (1.19%). The frequencies of ADRs tended to increase with age and stage of chronic kidney disease. The reductions in mean HbA1c after starting canagliflozin were maintained for up to 3 years with a mean change of - 0.68% (n = 6345 at 3 years). Maintained reductions in mean HbA1c were observed in each age subgroup and in patients with G1-G3b renal function.ConclusionThis surveillance in real-world clinical practice showed that canagliflozin provides sustained glucose-lowering effects in patients with T2DM, including elderly patients and patients with moderate renal impairment, without new safety concerns beyond those already described in the Japanese package insert.Trial registrationJapicCTI-153048.
| S-EPMC8799573 | biostudies-literature