Novartis (South Korea)

BACKGROUND: Statistical independence means that one observation is not affected by another; however, the principle of statistical independence is violated if left and right-side measures within a subject are considered to be independent, because they are usually correlated and can affect each other. The purpose of the present study was to analyze the violation of statistical independence in recent orthopaedic research papers and to demonstrate the effect of statistical analysis that considered the data dependency within a subject. METHODS: First, all original articles that had been published in The Journal of Bone and Joint Surgery (American Volume) over a two-year period were evaluated. The analysis was designed to identify articles that included bilateral cases and possible violations of statistical independence. Second, a demonstrative logistic regression without consideration of statistical independence was performed and was compared with a statistical analysis that considered data dependency within a subject. Radiographs of 1200 hips in 600 patients were used to examine the differences in terms of odds ratios (with 95% confidence intervals) of the risk factors for hip osteoarthritis. RESULTS: Four hundred and eighty-six original articles were reviewed, and 151 articles (including forty-one articles involving the hip, thirty-four involving the knee, twenty-one involving the foot or ankle, nineteen involving the shoulder, ten involving the hand or wrist, nine involving the elbow, and seventeen involving other structures) were considered to include bilateral cases. Of the 486 articles that were reviewed, 120 articles (25%) (including thirty-six articles involving the hip, twenty-six involving the knee, fifteen involving the foot or ankle, fourteen involving the shoulder, seven involving the elbow, six involving the hand or wrist, and sixteen involving other structures) were found to have possibly violated statistical independence. Demonstrative statistical analysis showed that logistic regression was not robust to the violation of statistical independence. The 95% confidence intervals of the odds ratios for the risk factors showed narrower ranges (1.13 to 2.68 times) when data dependency within a subject was not considered. CONCLUSIONS: Researchers need to consider statistical independence when performing statistical analysis, particularly in studies involving bilateral cases. If data dependency within a subject is not considered, studies involving bilateral cases can bias results, depending on the context of those studies.

BACKGROUND/AIMS: To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. METHODS: This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. RESULTS: A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. CONCLUSION: This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

OBJECTIVES: This study documents the incidences of agranulocytosis and neutropenia, and the patterns of incidence of the side effects of long-term clozapine treatment in order to determine an appropriate time to stop the Clozaril Patient Monitoring System (CPMS). METHODS: Hematological, demographic, and other data from the CPMS for 6782 patients who took clozapine for the past 11 years in the Republic of Korea has been analyzed. RESULTS: Twenty-nine (53.7%) of fifty-four agranulocytosis cases occurred within the first 18 weeks. The cumulative incidence of agranulocytosis was 1.64% between 6 and 11 years and the crude incidence was 0.8%. Neutropenia occurred in 697 patients, and 365 (52.4%) of these cases occurred within the first 18 weeks. The cumulative incidence of neutropenia was 19.8% between 8 and 11 years, and the crude incidence was 10.3%. There were no cases of agranulocytosis or neutropenia after the 9th year of clozapine treatment. CONCLUSIONS: The incidence of agranulocytosis in the Republic of Korea was similar to those in the rest of the world. While agranulocytosis began several years after clozapine treatment, long-term monitoring of white blood cells is necessary. We suggest that the CPMS should be stopped or less frequently after the 9th year of treatment.

Background and objective: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. Methods: This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George’s Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks. Results: Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P <0.001). Statistically significant improvement in transition dyspnea index score (TD =0.78, P <0.05) and numerical improvement in St George’s Respiratory Questionnaire for COPD score (TD =-2.36, P =0.3563) were observed with indacaterol versus placebo at Week 8. Incidence of adverse events was comparable between the treatment groups. Conclusion: Indacaterol provided significantly superior bronchodilation, significant improvement in breathlessness and improved health status with comparable safety versus placebo in Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. Keywords: indacaterol, COPD, tuberculosis, airflow limitation, lungs

To evaluate the real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) in Korea, focusing on retinal fluid resolution. This multi-institutional retrospective chart review study, analyzed medical records of patients with nAMD (age ≥ 50 years) who received their first anti-vascular endothelial growth factor (VEGF) treatment in ophthalmology clinics across South Korea between January 2017 and March 2019. The primary endpoint was the proportion of patients with retinal fluid after 12 months of anti-VEGF treatment. The association between fluid-free period and VA gains was also evaluated. A total of 600 patients were enrolled. At baseline, 97.16% of patients had retinal fluid; after 12 months of anti-VEGF treatment, 58.10% of patients had persistent retinal fluid. VA improvements were relatively better in patients with absence of retinal fluid compared with presence of retinal fluid (+ 12.29 letters vs. + 6.45 letters at month 12; P < .0001). Longer duration of absence of retinal fluid over first 12 months correlated with better VA gains at month 12 (P < .01). More than half of the study patients with nAMD had retinal fluid even after 12 months of treatment with their current anti-VEGF. Presence of retinal fluid was associated with relatively worse VA outcomes.

Bronchodilators provide improvements in lung function and reductions in symptoms and exacerbations, and are the mainstay of pharmacological management of chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease strategy recommends the use of a combination of long-acting β₂-agonist/long-acting muscarinic antagonists (LABA/LAMA) as the first-line treatment option in the majority of symptomatic patients with COPD. This review provides an indirect comparison of available LABA/LAMA fixed-dose combinations (FDCs) through discussion of important efficacy and safety data from the key literature, with the objective of providing physicians with a framework for informed decision-making. LABA/LAMA FDCs provided greater benefits compared with placebo and similar or greater benefits compared with tiotropium and salmeterol/fluticasone in improving lung function, dyspnea, health-related quality of life, reducing rescue medication use and preventing exacerbations, although with some variability in efficacy between individual FDCs; further, tolerability profiles were comparable among LABA/LAMA FDCs. However, there is a disparity in the amount of evidence generated for different LABA/LAMA FDCs. Thus, this review shows that all LABA/LAMA FDCs may not be the same and that care should be taken when extrapolating individual treatment outcomes to the entire drug class. It is important that physicians consider the efficacy gradient that exists among LABA/LAMA FDCs, and factors such as inhaler devices and potential biomarkers, when choosing the optimal bronchodilator treatment for long-term management of patients with COPD.

Abstract Abstract 2765 In CML, achievement of major molecular response (MMR) is a significant prognostic factor as it has been shown to be associated with longer duration of complete cytogenetic response (CCyR) and long-term progression-free survival. In IRIS study, patients who achieved both CCyR and MMR showed higher progression-free survival rates, compared to those who had CCyR without MMR. Higher doses of imatinib are expected to yield higher CCyR and MMR rates, compared to standard dose of imatinib, and second-generation tyrosine kinase inhibitor, nilotinib also produces high CCyR and MMR rates in patients with CP CML who are resistant to imatinib. In this prospective study, the efficacy of nilotinib and high-dose imatinib was investigated in suboptimal molecular responders who received standard-dose imatinib as first-line therapy. Early CP CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months (≥ 18 to ≤ 24 months) on first-line imatinib therapy at a daily dose of 400 mg were enrolled in this clinical trial, and informed consents were obtained from all patients prior to participation. In nilotinib arm, patients received oral dose of 400 mg BID (800 mg/day), and patients received 800 mg/day administrated as 400 mg BID in imatinib dose-escalation arm. To assess the drug efficacy, cytogenetics and RQ-PCR analysis were performed at regular intervals, and baseline mutational analysis was conducted for every patient with subsequent mutational analyses performed in patients demonstrating either lack of response or disease progression. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative CMR rates and time to and duration of MMR and CMR during further 24 month follow-up. Progression-free survival and safety profiles will also be assessed as secondary endpoints. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to crossover to the alternative treatment arm. With a data cut-off date of 18 Jul 2011, a total of 30 patients were randomized into nilotinib arm (n =13) or imatinib arm (n = 17), and 6 patients have crossed-over to nilotinib arm due to lack of response. With a median follow-up of 11 months (range, 0.2–28 mos), all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR-ABL transcript levels was observed in all patients. Cumulative MMR rates at 20 months were significantly higher in nilotinib arm compared to imatinib dose-escalation arm (59.00% vs. 27.40%, P = 0.047), and patients treated with nilotinib also showed faster molecular response rates, with 5 patients achieving MMR within 3 months of nilotinib therapy. At the last follow-up, 7/13 (53.85%) and 2/11 (18.18%) patients achieved MMR in nilotinib arm and in high-dose imatinib arm, respectively, with 1 patient in nilotinib arm achieving 4-log reduction of BCR-ABL transcripts. Although toxicity was observed more frequently in imatinib dose-escalation arm, all patients currently maintain the initial dose (except 1 patient who interrupted imatinib therapy due to neurosurgical operation), and based on the toxicity data, no additional or serious adverse events were developed except for pre-existing toxicities before randomization. These preliminary results demonstrate that early intervention using nilotinib or dose escalation of imatinib could be recommended in suboptimal molecular responders, with nilotinib being more preferable. Through further clinical investigation on a large patient population and longer period of observation, efficacy and safety of early intervention of suboptimal molecular response using nilotinib or dose escalation of imatinib will be assessed. Updated data with longer follow-up duration will be presented in the meeting. Disclosures: Woodman: Novartis: Employment, Equity Ownership. Szczudlo:Novartis: Employment, Equity Ownership. Kim:Novartis: Employment.

Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μ g/mL of moxifloxacin; 93.6%, 1.0 μ g/mL of levofloxacin; 97.5%, 2.5 μ g/mL of kanamycin; 90.6%, 2.5 μ g/mL of capreomycin; 86.2%, 5.0 μ g/mL of ethionamide; and 90.8%, 2.0 μ g/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ -aminosalicylic acid is required.

Objective: This study aims to provide an up-to-date analysis of the current state of patient access to new drugs in South Korea, focusing on the effect of new review pathways for reimbursement.Methods: We analyzed patients’ access to new drugs, listing rate and lead time until listing from marketing authorization. New pathways were defined as ‘price negotiation waiver,’ ‘risk-sharing agreements,’ and ‘pharmacoeconomic evaluation exemption.’Results: The listing rate for drugs increased after the introduction of the new pathways (93.7% vs. 77.9%, p < 0.001). Before the new pathways, the median lead time for listing was 21.0 months (95% CI: 16.9–25.0), while afterward it was shortened to 10.9 months (95% CI: 10.2–11.7) (p < 0.001).Conclusion: Although it has strengthened national health insurance coverage by positively impacting the rate and lead time, the lead time for the oncology and orphan drugs is substantially longer as compared to other drugs. Expanding the eligibility criteria to include non-life-threatening but rare or intractable diseases, and resolving the system’s operational issues are still necessary.

Objective: This study aimed to examine patient accessibility to new anticancer drugs including reimbursement coverage, time to listing, and listing price during the recent 3 years after the introduction of alternative pricing and reimbursement pathways in South Korea.Methods: Anticancer drugs were selected for analysis from the new drugs reviewed from January 2017 to March 2020. Descriptive statistics were used to present the levels of the listing prices. Pearson’s correlation analysis was used to analyze the relationship between the list price in comparison to the External Reference Price(ERP) and the time to listing.Results: Thirty-two anticancer drugs were included in analysis. The average time to listing for these drugs was 36.7 months. The ratio of the listing price in comparison with Average Adjusted Price from seven reference countries was from 12.6% to 90.2%. Pearson’s correlation coefficient for the correlation between the ratio of the listing price to the ERP and the time to listing was −0.37 and was statistically significant (p = 0.035).Conclusions: Policies that relate to the scope of reimbursement, time to reimbursement, and list price should be able to equally reflect patient accessibility and national health insurance finances, as well as the impact on industry as a whole.

PURPOSE: To investigate the short-term efficacy and safety of ranibizumab in the routine clinical setting in patients with neovascular age-related macular degeneration and to analyze the associated factors for visual outcome. METHODS: This was a post-hoc analysis of a ranibizumab regulatory post-marketing surveillance study in which 4,136 patients were enrolled and followed for 12 weeks. Change in best-corrected visual acuity (BCVA), size of choroidal neovascularization, and the presence of hemorrhage and exudate were analyzed and the association between BCVA change and baseline characteristics were investigated. Data on ocular and systemic adverse events were collected. RESULTS: < 0.001). A lower baseline BCVA and younger age were significant predictive factors for visual improvement or maintenance (≥0 lines). For greater visual acuity gain (≥3 lines), no treatment history, lower baseline BCVA, younger age, and classic-type choroidal neovascularization were significant predictive factors. No new safety signals were found. CONCLUSIONS: In this study, conducted in real-world clinical practice with a large number of neovascular age-related macular degeneration patients, visual and anatomical outcomes improved significantly after three monthly ranibizumab treatments. Treatment-naive patients had a higher chance of greater visual gain (≥3 lines) than non-naive patients.

BACKGROUND: -agonist, is approved in over 100 countries, including South Korea, as a once-daily bronchodilator for maintenance and treatment of chronic obstructive pulmonary disease (COPD). Here, we present an interim analysis of a post-marketing surveillance study conducted to evaluate the real-world safety and effectiveness of indacaterol in the Korean population. METHODS: This was an open-label, observational, prospective study in which COPD patients, who were newly prescribed with indacaterol (150 or 300 µg), were evaluated for 12 or 24 weeks. Safety was assessed based on the incidence rates of adverse events (AEs) and serious adverse events (SAEs). Effectiveness was evaluated based on physician's assessment by considering changes in symptoms and lung function, if the values of forced expiratory volume in 1 second were available. RESULTS: Safety data were analyzed in 1,016 patients of the 1,043 enrolled COPD patients receiving indacaterol, and 784 patients were included for the effectiveness analysis. AEs were reported in 228 (22.44%) patients, while 98 (9.65%) patients reported SAEs. The COPD condition improved in 348 patients (44.4%), while the condition was maintained in 396 patients (50.5%), and only 40 patients (5.1%) exhibited worsening of ailment as compared with baseline. During the treatment period, 90 patients were hospitalized while nine patients died. All deaths were assessed to be not related to the study drug by the investigator. CONCLUSION: In real-life clinical practice in South Korea, indacaterol was well tolerated in COPD patients, and can be regarded as an effective option for their maintenance treatment.

Purpose: BRAF mutations are found in 1–5% of non-small cell lung cancers, particularly adenocarcinomas. However, information regarding this mutation is limited in patients without EGFR/ALK aberrations, who have limited treatment options. Patients and methods: The medical records of 224 stage III/IV adenocarcinoma patients without EGFR/ALK aberrations and with available pathologic tissue, were retrospectively reviewed. BRAF mutations were evaluated using a PNAClamp TM, BRAF mutation detection kit (Panagene, Daejeon, Korea). The outcomes in the study population were compared with stage III/IV adenocarcinoma patients harboring an EGFR mutation. A case report of targeted therapy against BRAF mutations was also presented. Results: A cohort of 222 adenocarcinoma patients with adequate pathologic tissue samples was analyzed. The median patient age was 63 years, 68.8% of the patients were male and 68.7% were ever-smokers. The V600E BRAF mutation was detected in 4 patients (1.8%). The 222 study patients had a poorer survival outcome compared to stage III/IV adenocarcinoma patients with an EGFR mutation (median, 12 vs 67 months, P <0.001) from a recent previous study. Moreover, a 47-year-old female with a recurrent adenocarcinoma and a BRAF V600E mutation exhibited tumor regression after a fourth line therapy with dabrafenib and trametinib, targeting agents against BRAF mutations. Conclusion: Although BRAF mutations are found in 1.8% of advanced adenocarcinoma patients without EGFR/ALK aberration, they may be able to serve as a treatment target in those patients. Keywords: BRAF, adenocarcinoma, lung cancer

BACKGROUND: This descriptive epidemiological study aimed to assess the prevalence of serum bactericidal antibodies against Neisseria meningitidis serogroups A, C, W and Y in adolescents and adults in the Republic of Korea. MATERIALS AND METHODS: In total, 987 subjects aged 11-55 years from five geographical regions of Korea were included in the study. Human serum bactericidal assay (hSBA) was used to measure hSBA titres for serogroups A, C, W and Y. Percentages of subjects with hSBA titres ≥4 and ≥8, geometric mean titres (GMTs), and associated 95% confidence intervals (CIs), were estimated. Analysis was performed for the entire study population and stratified by age group or region. No statistical hypotheses were tested. RESULTS: The highest percentage of subjects with hSBA titres ≥8 was observed for serogroup W (74%), was similar for serogroups C (34%) and Y (36%), and was lowest for serogroup A (9%). The percentages of subjects with hSBA titres ≥4 were similar to those with hSBA titres ≥8 for all serogroups. GMTs were 2.56 µg/mL (serogroup A), 5.14 µg/mL (serogroup C), 22.63 µg/mL (serogroup W) and 5.28 µg/mL (serogroup Y). Similar trends in GMTs across serogroups were seen for individual regions and age groups. The highest GMTs for serogroups A, W and Y were recorded in the >19-29 years group, and for serogroup C in the >49-55 years group. Across all regions, GMTs were very similar for serogroups A, C and Y, while more variation was seen for serogroup W. CONCLUSION: In the Korean population, among Neisseria meningitidis serogroups A, C, W and Y, serum bactericidal antibodies were most prevalent against serogroup W and least prevalent against serogroup A. These trends were maintained across age groups and regions. The highest GMTs for serogroups A, W and Y were observed in the >19-29 years group. The reasons behind the observed differences in prevalence of bactericidal antibodies against the serogroups are currently not understood, although carriage and cross-reactivity of the assay may be important influences.

Purpose: To evaluate the real-world effectiveness, treatment patterns, and safety of ranibizumab in Korean patients with neovascular age-related macular degeneration (nAMD). Methods: LUMINOUS™ is a 5-year, global, prospective, observational, open-label study. Adults aged ≥ 18 years who were either treatment-naïve or prior-treated were enrolled and treated with ranibizumab 0.5 mg as per the local label. Outcome measures included mean (± standard deviation [SD]) changes from baseline in visual acuity (VA) and central retinal thickness (CRT), and rate of ocular and non-ocular adverse events (AEs). Results: Overall, 367 Korean patients with nAMD (152 treatment-naïve and 215 prior-treated) were enrolled. The mean (SD) VA changes from baseline at 1-year were +10.1 (± 21.77; P =0.0005) and +1.4 (± 15.17; P =0.2142) Early Treatment Diabetic Retinopathy Study letters, with mean numbers of injections of 5.2 and 3.4 in the treatment-naïve and prior-treated groups, respectively. VA gains were greater in patients with lower baseline VA, who received a loading dose, and with polypoidal choroidal vasculopathy (PCV). Multivariate logistic regression analyses demonstrated younger age, worse baseline VA, and those who received loading dose being associated with higher odds of any gain in VA at 1 year ( P < 0.05). Mean (SD) CRT changes from baseline were – 126.7 (± 174.90) μm ( P < 0.0001) and +10.8 (± 89.62) μm ( P =0.5833) in the treatment-naïve and prior-treated groups, respectively, with greater reductions observed in patients with PCV. Ocular and non-ocular AEs were reported in 8.4% (n=31) and 10.1% (n=37) of patients, respectively. Conclusion: The LUMINOUS study confirms real-world effectiveness and safety of ranibizumab in Korean patients with nAMD; factors including age, baseline VA, and loading-dose were associated with VA gain at one-year post-treatment. Keywords: neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, ranibizumab, real-world

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

AIM: This study aimed to describe characteristics, treatment patterns and survival among Korean patients diagnosed with locally advanced or metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A retrospective patient chart review was conducted in major cancer centers in Korea in 2014-2015. Participating physicians reviewed patient charts and reported characteristics, treatment patterns, clinician-defined progression-free survival (PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC patients. PFS and OS were estimated using Kaplan-Meier analysis. RESULTS: Physicians reported on 55 ALK+ NSCLC patients. Median age at locally advanced or metastatic NSCLC diagnosis was 60 years. Most patients (82%) received initial chemotherapy; 13% received an ALK inhibitor in the first line; 62% received an ALK inhibitor by the end of follow-up. Of the 30 patients who received crizotinib, 83% discontinued and 13% died during crizotinib therapy. Median PFS on crizotinib was 6.7 months. Of those who discontinued, 32% switched to chemotherapy, 16% switched to a different ALK inhibitor and 52% received no further therapy. After discontinuing crizotinib, median OS was 6.0 months overall, and 3.4 months among patients who did not receive a second-generation ALK inhibitor. CONCLUSION: In this study of locally advanced or metastatic ALK+ NSCLC patients in Korea, roughly one-third did not receive an ALK inhibitor. Among patients who discontinued crizotinib, over half received no further antineoplastic therapy and OS was poor, particularly among patients without second-generation ALK inhibitor use. These findings suggest a need for greater access to effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.

BACKGROUND: The demand for implementing a new listing scheme to expedite patient access to novel oncology drugs has increased in South Korea. This study was conducted to compare the prices of anticancer drugs between eight countries and to explore the feasibility of a 'pre-listing and post-evaluation' scheme to expedite patient access to oncology drugs. METHODS: This study included 34 anticancer drugs, which were reimbursed between 1 January 2007 and 31 December 2017. The unit price and sales volume of the study drugs were collected from eight countries and IQVIA data, respectively. The prices were adjusted to estimate the ex-factory prices using the discount/rebate rate suggested by the Health Insurance Review Agency (HIRA). The four price indices of Laspeyres, Paasche, Fisher, and the unweighted index were calculated using the price in each country, the average price, and lowest price among the study countries. Each currency was converted using the currency exchange rate and purchasing power parity (PPP). The budget impact of implementing the proposed pre-listing and post-evaluation scheme on payers was calculated. RESULTS: Based on the currency exchange rate, anticancer drug prices were higher in other countries (index range: 1.05-2.78) compared to Korea. The prices in Korea were similar to countries with the lowest prices. When the PPP was applied, prices were higher in the US, Germany, Italy, and Japan than in Korea (range: 1.10-2.13); however, the prices were lower in the UK, France, and Switzerland than in Korea (range: 0.72-0.99). The financial burden of implementing the pre-listing and post-evaluation scheme was calculated at 0.83% of the total anticancer drug sales value in Korea from 2013-2017. CONCLUSIONS: The prices of anticancer drugs in Korea were similar to the lowest prices among the seven other study countries. A pre-listing and post-evaluation scheme should be considered to improve patient access to novel anticancer drugs by reducing the reimbursement review time and uncertainties.

The present observational study aimed to evaluate the clinical effectiveness of vildagliptin with metformin in Korean patients with type 2 diabetes mellitus (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective observational study of vildagliptin/metformin (fixed DC or free DC). The effectiveness endpoint was the proportion of patients who achieved a glycemic target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the analysis; of these, 2087 patients were eligible. The mean patient age was 56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0% at 24 weeks. The glycemic target achievement rate was significantly greater in patients with baseline HbA1c &lt; 7.5% versus ≥7.5% (84.64% versus 43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%). Multivariate logistic regression analysis indicated that disease duration (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), baseline HbA1c (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), and DC type (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0103</mml:mn></mml:math>) had significant effects on drug effectiveness. Vildagliptin plus metformin appeared as an effective treatment option for patients with T2DM in clinical practice settings in Korea.

AIM: To compare the cost-effectiveness of secukinumab vs adalimumab at 1 and 2 years of treatment in patients with ankylosing spondylitis (AS) by analyzing the cost per responder reported in randomized controlled trials (RCTs) from the Korean perspective. METHOD: A systematic literature search was performed via PubMed for relevant RCTs for comparing the response rate in patients with AS. The response rates in anti-tumor necrosis factor-naive subjects were extracted from RCTs and cost per responder analyses were calculated in case of both with or without a loading dosage of secukinumab compared with adalimumab. RESULTS: The Assessment in AS International Working Group (ASAS) 20 and 40 response rates of secukinumab from the MEASURE 2 trial and those of adalimumab from the ATLAS trial were comparable. The cost per ASAS 20 responder was lower by 40% in secukinumab compared to adalimumab: USD9637 vs 16 129 at 52 weeks and USD20 051 vs 32 699 at 104 weeks for secukinumab (in maintenance dosing) vs adalimumab, respectively. The cost per ASAS 40 responder was also lower by 40% in secukinumab: USD12 179 vs 22 395 at 52 weeks and USD27 338 vs 41 655 at 104 weeks for secukinumab vs adalimumab, respectively. With a loading dosage of secukinumab at 52 and 104 weeks, secukinumab showed lower costs per responder by 25% compared to adalimumab. CONCLUSION: The costs per responder associated with ASAS 20 and 40 response rates were consistently lower for secukinumab compared with adalimumab. The treatment with secukinumab for patients with AS could be a cost-saving treatment option in South Korea.