Treatment Of Korean Patients Research Articles

Bimekizumab efficacy and safety in Korean patients with moderate to severe plaque psoriasis: A phase 3, randomized, placebo-controlled, double-blinded study.

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co-primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co-primary efficacy end points was performed using a type I error rate, at a two-sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab-treated patients had significantly higher clinical responses versus placebo-treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab-treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health-related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well-tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well-tolerated treatment option in Korean patients with psoriasis.

Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program.

The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP). This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice. Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died. Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.

THU428 Association Of Bone Turnover Markers Monitoring With Osteoporosis Medication Adherence In Korea: A Nationwide Cohort Study

Abstract Disclosure: S. Ahn: None. S. Park: None. M. Kwak: None. S. Kim: None. T. Kim: None. H. Kim: None. S. Hong: None. Objective: Bone turnover markers (BTMs) are non-invasive and useful biomarkers for predicting the risk of fractures and monitoring the adherence and response to medical treatment in patients with osteoporosis. However, the contribution of BTMs in the improvement of osteoporosis medication adherence has not been well studied. Therefore, we investigated the association of BTMs monitoring with medication adherence in Korean osteoporosis patients. Methods: We used data from the Korean National Health Insurance Service. Among 1,440,538 osteoporosis patients ≥50 years who started with medical treatment during 2010-2014, we selected 118,598 patients who monitored BTMs at least once during 2 years of follow up (BTM group) and 362,794 age-, sex-, and medication initiation year-matched controls who never measured BTMs (NO-BTM group). Adherence to medical treatment was defined as medication possession ratio ≥80%. Multivariable logistic regression analysis was used to determine the association of BTMs monitoring with adherence at 2 year follow up. Results: Among BTM group, 92.5% and 87.1% patients monitored bone resorption or formation markers at least once during 2 years of follow up, respectively. However, only 36.0% of patients monitored BTMs more than twice. MPRs at 2 year follow up were higher in BTM group than in NO-BTM group (41.4% vs. 26.5%, P&amp;lt;0.001). Among BTM group, MPRs were higher in patients who monitored bone resorption markers than in patients who never monitored them (41.7% vs. 36.1%, P&amp;lt;0.001) and in patients who monitored BTMs more than twice than in patients who monitored them only once (55.6% vs. 32.9%, P&amp;lt;0.001). BTMs monitoring showed positive association with MPRs at 2 year follow up (β = 3.055, SE = 0.137, P&amp;lt;0.001) after adjusting for confounders. BTMs monitoring was associated with increased OR (1.17, 95% CI 1.15-1.20, P&amp;lt;0.001) for better adherence to medical treatment at 2 year follow up after adjusting for confounders. Conclusion: In this retrospective study, monitoring of BTMs was associated with better adherence to medical treatment in Korean patients with osteoporosis. Presentation: Thursday, June 15, 2023

Increased risk of herpes zoster with tofacitinib treatment in Korean patients with rheumatoid arthritis: a single-center prospective study

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study.

Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

A retrospective observational study of the appropriate starting dose of febuxostat in patients with gout.

The occurrence of gout attacks at the start of uric acid lowering treatment worsens compliance. We aimed to determine the appropriate dose of febuxostat to reduce the occurrence of gout attacks during the initial treatment period. We retrospectively analyzed the data of patients diagnosed with gout who underwent treatment at Jeju National University Hospital between May 2018 and May 2020. Two-hundred and twenty-seven patients were included, with a mean age of 53.2 ± 16.4 years, and 219 (96.5%) were male. The patients were divided into two groups according to the starting dose of febuxostat (20 mg vs. 40 mg). There were no significant differences in mean age, disease duration, colchicine, estimated glomerular filtration rate (eGFR), initial uric acid levels, and presence of subcutaneous tophi between the two groups. Gout attacks occurred more frequently in the 20 mg group than in the 40 mg group during the first 3 months of treatment (32.0% vs. 14.3%, p = 0.002), particularly during the first month (21.3% vs. 7.5%, p = 0.005). Multivariate logistic regression analysis was conducted adjusting for the effects of disease duration, the presence of subcutaneous tophi, eGFR, and initial uric acid levels. A febuxostat starting dose of 40 mg (odds ratio, 0.464; 95% confidence interval [CI], 0.246 to 0.862; p = 0.015) and anti-inflammatory prophylaxis (odds ratio, 0.359; 95% CI, 0.158 to 0.813; p = 0.014) were found to be independent factors associated with a gout attack. Starting uric acid lowering treatment with febuxostat 40 mg rather than 20 mg may reduce the incidence of gout attacks in the early period of treatment in Korean patients with gout.

Assessing the Effectiveness and Safety of Direct-acting Antiviral Treatment in Korean Patients with Hepatitis C Virus Genotype 1b or 2 at a Tertiary Care Hospital

Assessing the Effectiveness and Safety of Direct-acting Antiviral Treatment in Korean Patients with Hepatitis C Virus Genotype 1b or 2 at a Tertiary Care Hospital

Efficacy and tolerability of fremanezumab for migraine preventive treatment in Korean patients with chronic or episodic migraine

Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy in patients with chronic and episodic migraine (CM and EM). Efficacy and tolerability of fremanezumab for migraine preventive treatment in Korean patients with CM and EM have been evaluated in two randomized, double-blind, placebo-controlled phase 2b/3 clinical studies and compared with data from pivotal phase 3 HALO CM and HALO EM studies.

Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients.

BACKGROUNDAntibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention. AIMTo investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen. METHODSWe included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen. RESULTSOf the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).CONCLUSIONThe DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.

Population Pharmacokinetics of Primaquine in the Korean Population.

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score (p < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.

Real-World Outcomes of Pazopanib Treatment in Korean Patients with Advanced Soft Tissue Sarcoma: A Multicenter Retrospective Cohort Study.

Pazopanib is the only tyrosine kinase inhibitor approved for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy, but there have been limited real-world data on pazopanib for the treatment of advanced STS. We aimed to evaluate clinical outcomes of pazopanib in patients with multiple histologic STS types in real-world settings. We retrospectively analyzed clinical data of Korean patients with advanced STS treated with pazopanib between 2008 and 2019. Outcomes of interest included treatment response, survival according to histologic subtypes, and adverse events. The analysis included 347 STS patients. The disease control rate for all pazopanib-treated patients was 54.8% (95% confidence interval (CI) 49.5-60.0); 54 patients (15.6%) achieved a partial response and 136 (39.2%) had stable disease. Patients with alveolar soft-part sarcoma (ASPS; 90%), solitary fibrous tumor (SFT; 88.2%), synovial sarcoma (66.7%), leiomyosarcoma (61.1%), and undifferentiated pleomorphic sarcoma (59.6%) showed higher disease control rates than those with other STS subtypes. Overall, median progression-free survival (PFS) and overall survival (OS) were 5.3months (95% CI 4.5-6.0) and 12months (95% CI 10-14), respectively. Noticeable survival outcomes occurred in patients with ASPS and SFT, with a median PFS of 24.5 (95% CI 2.5-30.0) and 13.0 (95% CI 3.0-21.3) months, respectively. The median OS of patients with ASPS and SFT was 48 (95% CI 17-52) and 32 (95% CI 19-66) months, respectively. Adverse drug reactions occurred in 170 patients (49.0%) but were not life-threatening. This real-world data analysis showed acceptable efficacy and tolerability of pazopanib in patients pretreated with cytotoxic chemotherapy for advanced STS, with favorable treatment outcomes for ASPS and SFT.

Long-term hepatitis B surface antigen (HBsAg) kinetics during entecavir treatment in Korean patients-Functional cure unlikely.

The aim of this study was to investigate the on-treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve functional cure. From a cohort of 1009 CHB treatment-naïve patients who were started on entecavir, the kinetics of quantitative HBsAg decline was assessed in 410 patients by a linear mixed model. The difference in the kinetics of quantitative HBsAg was determined based on the HBeAg positivity, HBeAg seroclearance and presence of baseline liver cirrhosis. Among the 410 patients, 213 patients (52.0%) were HBeAg-positive and 217 patients (66.1%) were male with a median age of 48years. During a median follow-up of 53.5months, the quantitative HBsAg level showed a slow but consistent decrease. The expected log qHBsAg levels as a function of time during entecavir treatment in HBeAg(+) and HBeAg(-) patients were 3.4773-0.0039×Months and 3.1853-0.0036×Months, respectively. The estimated time to clearance of quantitative HBsAg in our study was greater than 74.1years in HBeAg-positive patients and 73.5years in HBeAg-negative patients. The calculated time to achieve functional cure is lifelong without regard to HBeAg seroclearance or presence of liver cirrhosis. The mathematical modelling from a long-term follow-up of chronic hepatitis B patients on entecavir shows that HBsAg clearance requires decades of treatment. Thus, lifelong therapy is inevitable in entecavir-treated patients to achieve functional cure.

APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR.

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9-25.5, p < 0.001) increased risk of bleeding, and attributable risk was 88.3%. C allele carriers of c.1853C>T had 6.4 times (95% CI 2.3-17.9, p < 0.001) increased risk of bleeding after adjusting for covariates (attributable risk of 84.3%). AUROC values of models that included c.1853C>T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.

The predictors of sustained virological response with sofosbuvir and ribavirin in patients with chronic hepatitis C genotype 2.

Background/AimsReal-world, clinical practice data are lacking about sofosbuvir/ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment.MethodsA total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks.ResultsThe RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (–) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia.ConclusionsSOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.

Intensity of Statin Treatment in Korean Patients with Acute Myocardial Infarction and Very Low LDL Cholesterol.

ObjectiveData on the intensity of statin therapy for patients with acute myocardial infarction (MI) and very low baseline low-density lipoprotein (LDL) cholesterol level are lacking. We sought to assess the impact of statin intensity in patients with acute MI and LDL cholesterol <70 mg/dL.MethodsA total of 1,086 patients with acute MI and baseline LDL cholesterol <70 mg/dL from the Korea Acute Myocardial Infarction Registry-National Institute of Health database were divided into less intensive statin (expected LDL reduction <40%, n=302) and more intensive statin (expected LDL reduction ≥40%, n=784) groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, MI, revascularization occurring at least 30 days after admission, and stroke, at 12 months.ResultsAfter 1:2 propensity matching, differences were not observed between less intensive (n=302) and more intensive statin (n=604) groups in incidence of cardiac death (0.3% vs. 0.3%) and hemorrhagic stroke (0.3% vs. 0.5%, p=0.727) at 12 months. Compared with the less intensive statin group, the more intensive statin group showed lower target-vessel revascularization (4.6% vs. 1.8%, p=0.027) and MACCE (11.6% vs. 7.0%, p=0.021). Major bleeding was not different between less intensive and more intensive statin groups (1.0% vs. 2.6%, p=0.118).ConclusionMore intensive statin therapy was associated with significantly lower major adverse cardiovascular events in patients with acute MI and very low LDL cholesterol compared with less intensive statin therapy.

A 10-Year Trend in the Incidence and Treatment of Korean Patients with Mitral Stenosis and Atrial Fibrillation

A 10-Year Trend in the Incidence and Treatment of Korean Patients with Mitral Stenosis and Atrial Fibrillation

Scoring system for risk stratification of viral reactivation during prophylactic antiviral treatment in Korean patients with hepatitis B undergoing anticancer chemotherapy: A multicenter study.

Prophylactic antiviral therapy is recommended for hepatitis B virus (HBV)-infected patients with malignancies who are undergoing systemic chemotherapy. In the current study, we aimed to develop a risk scoring system to guide the selection of prophylactic antiviral agents. In this retrospective analysis, we included consecutive chronic hepatitis B patients who received antiviral prophylaxis for chemotherapy of solid or hematologic malignancies at three large-volume hospitals in Korea. The primary endpoint was HBV reactivation. The inverse probability treatment weighting method was used to minimize selection bias in terms of antiviral assignments. A total of 419 patients were enrolled: 129 patients received lamivudine (LAM), 216 received telbivudine (LdT), and 74 received entecavir (ETV), respectively. Of these, 36 patients developed on-treatment HBV reactivation (LAM, 17; LdT, 18; ETV, 1). Multivariate analysis identified three independent predictors for reactivation: hepatitis B e-antigen positivity, HBV DNA level, and type of malignancy. Accordingly, a risk scoring system was developed wherein one point was assigned for each of the risk factors. HBV reactivation occurred more frequently in the high-risk group (score ≥ 2) than in the low-risk group (hazards ratio, 14.17; P < 0.001). ETV exhibited superior prophylactic efficacy over LdT or LAM in the high-risk group, whereas no significant difference was noted in the low-risk group. The prognostic scoring system was useful for risk stratification of chemotherapy-related HBV reactivation. High genetic barrier agents appear to be vital for high-risk patients, whereas cost-effectiveness may be more relevant for low-risk patients.

Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study.

Background/AimsSofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection.MethodsWe retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area.ResultsA total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients.ConclusionsA 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.

Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial.

BackgroundThis is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.MethodsThis multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.ResultsEighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection.ConclusionIpragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea

Objectives: The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz) in Korean patients with overactive bladder (OAB) in routine clinical practice. Methods: This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator’s discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.Results: A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.Conclusion: These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.