Real-World Safety and Effectiveness of Infliximab in 255 Patients with Intestinal, Neurological, and Vascular Behçet's Disease: A Post-Marketing Surveillance.

INTRODUCTION: Behçet's disease (BD) with intestinal, neurological (NBD), and vascular (VBD) manifestations often leads to poor outcomes. Infliximab is approved for the treatment of intestinal BD, NBD, and VBD in Japan; however, evidence regarding its safety and effectiveness in these patients is limited. We conducted a 2-year post-marketing surveillance to evaluate the safety and effectiveness of infliximab in patients with intestinal BD, NBD, and VBD in Japan. METHODS: This 2-year, multicenter, prospective, observational study included all patients with intestinal BD, NBD, or VBD, who had experienced an insufficient response to conventional therapies (e.g., glucocorticoids and immunosuppressants/immunomodulators), and initiated infliximab for the first time at participating medical institutions. The safety endpoints included adverse events and adverse drug reactions (ADRs), and the effectiveness endpoints included global improvement, and for patients with acute NBD, acute attacks. RESULTS: Between October 2015 and August 2018, 255 patients (171 intestinal BD, 49 NBD, and 51 VBD; including 16 with two disease types) were enrolled from 133 medical centers and treated with infliximab. Adverse events, ADRs, and serious ADRs occurred in 100 (39.2%), 72 (28.2%), and 38 (14.9%) patients, respectively; incidences were generally similar across intestinal BD, NBD, and VBD groups. No new safety concerns were identified. At the final evaluation, 68.8% of patients with intestinal BD showed improvement, most patients with chronic progressive NBD and VBD had not worsened (100% and 91.7%, respectively), and 93.3% of patients with acute NBD had no new acute attacks during the observation period. CONCLUSION: These results confirmed the safety and effectiveness of infliximab in clinical practice in 255 patients with intestinal BD, NBD, and VBD. There were no new safety concerns.

Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).

BACKGROUND: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd. METHODS: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs). RESULTS: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected. CONCLUSIONS: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice. CLINICAL TRIAL REGISTRATION: UMIN000049032.

A prospective, observational, multi-center, post-marketing safety surveillance study of the GSK combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) in South Korean infants.

In South Korea, a combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) is available since 2018 for vaccination of infants from the age of 2 months. This prospective, observational, non-comparative, post-marketing study evaluated the real-world safety of DTaP-IPV/Hib primary vaccination in eligible South Korean infants from the age of 2 months between 2018 and 2022. Infants were followed up for 30 days after each vaccine dose to assess the proportion of infants experiencing any adverse event (AE), including adverse drug reactions (ADRs), unexpected AEs, and serious AEs/serious ADRs (SAEs/SADRs). Of 660 infants vaccinated during the study period, 646 were included in the total safety cohort. A total of 194 AEs were reported in 143 (22.1%) infants; 158 AEs occurred after the first dose in 130 (20.1%) infants, 21 after the second dose in 20 (13.4%) infants, and 11 after the third dose in ten (8.1%) infants. The most frequent AEs by Medical Dictionary for Regulatory Activities Preferred Terms terminology were pyrexia (13.3%), injection site swelling (5.1%), and irritability (1.7%). Most of the AEs were mild, resolved without a medical visit, and were classified as possibly related to vaccination. The incidence proportions of ADRs, unexpected AEs, and SAEs/SADRs were 19.4%, 4.3%, and 0.9%, respectively. All SAEs/SADRs resolved after hospitalization or emergency room visit, and one event was possibly related to vaccination. These results are in line with the approved label and other national/international studies, confirming the acceptable safety profile of DTaP-IPV/Hib in the South Korean pediatric population.

In South Korea, a vaccine to help protect infants against five childhood diseases (diphtheria, tetanus, whooping cough, poliomyelitis, and Haemophilus influenzae type b invasive infections) called DTaP-IPV/Hib vaccine, has been available since 2018. As required by Korean regulation, this study aimed to confirm that DTaP-IPV/Hib was well tolerated by South Korean infants during its first 4 years of use in the country (2018­2022). This study followed 646 healthy infants aged 2­3 months who received up to three vaccine doses with 2-month intervals between doses, according to the Korean vaccination recommendations. The infants were followed for 30 days after each vaccination to evaluate how often adverse events (AEs) occurred during that period. An AE was defined as any untoward medical event after exposure to the vaccine, but not necessarily caused by that same vaccine. Overall, 194 AEs occurred during the study. On average, at least one AE was reported in 22% of infants within 30 days following vaccination. These AEs were mostly fever (body temperature >38.0°C), swelling at vaccine injection site, and irritability. A serious AE (SAE) was reported for 0.9% of infants. The infants always recovered from these SAEs after hospitalization or emergency room visit. The reported AEs are indicated in the vaccine package insert, meaning they were possibly expected to occur after vaccination. This study therefore confirms the acceptable safety profile of DTaP-IPV/Hib when given to South Korean infants in accordance with local prescribing recommendations and as part of routine childhood immunization.

Post-marketing surveillance framework of cell and gene therapy products in the European Union, the United States, Japan, South Korea and China: a comparative study.

BACKGROUND: Cell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs. METHODS: Related regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan's Pharmaceuticals and Medical Device Agency, South Korea's Ministry of Food and Drug Safety, and the National Medical Products Administration of China. RESULTS: Compared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance. CONCLUSIONS: This study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China's future learning and development in this field.

Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study.

OBJECTIVE: This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice. METHODS: Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were followed up for 6 months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected. RESULTS: This PMS enrolled 124 patients, involving 48 sites across Japan. At 6 months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics. CONCLUSION: The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.

Post-Marketing Surveillance of Adverse Events Following Immunization with Haemophilus Influenzae Type b Conjugate Vaccine - China, 2010-2021.

Introduction: The Haemophilus influenzae type b (Hib) conjugate vaccine is widely administered in China. Methods: We extracted data on Hib vaccine doses administered and adverse events following immunization (AEFI) reported between 2010 and 2021 from the Chinese National Immunization Information System (CNIIS). A descriptive analysis was conducted to examine the characteristics and incidence rates of AEFI with the Hib vaccine. Results: In China, between 2010 and 2021, a total of 52,910 AEFIs with the Hib vaccine were reported, resulting in an overall AEFI reporting rate of 38.10 per 100,000 doses. Common (typically minor) and rare (potentially serious) vaccine reactions occurred at rates of 34.71 and 2.78 per 100,000 doses, respectively. Among the common vaccine reactions, the incidences of fever (axillary temperature ≥38.6 ℃), injection site redness and swelling (>2.5 cm in diameter), and injection site induration (>2.5 cm in diameter) were 11.93, 9.69, and 3.38 per 100,000 doses, respectively. Rare vaccine reactions included anaphylactic rash, angioedema, and febrile convulsion with reported incidences of 2.42, 0.10, and 0.05 per 100,000 doses, respectively. The incidence of serious rare vaccine reactions was 0.16 per 100,000 doses. Conclusions: The reported incidence of AEFI with the Hib vaccine was low, with the occurrence of serious rare adverse reactions also being markedly low throughout the period 2010-2021 in China.

Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine.

INTRODUCTION: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. KETAMINE AND ESKETAMINE: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. MISUSE AND ABUSE OF KETAMINE AND ESKETAMINE: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. DISCUSSION: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? CONCLUSIONS: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.

Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to identify the safety and effectiveness of tofacitinib in patients with UC in routine clinical settings in Korea. METHODS: This open-label, observational, prospective, post-marketing surveillance study was conducted at 22 hospitals in the Republic of Korea. Patients with moderate to severe active UC who received tofacitinib were included and followed up for up to 52 weeks. Tofacitinib was administered at a dosage of 10 mg twice daily for at least 8 weeks, followed by 5 or 10 mg twice daily at the investigator's discretion based on clinical evaluation according to the approved Korean label. Safety including adverse events (AEs) and effectiveness including clinical remission, clinical response, and endoscopic mucosal healing were evaluated. Safety analysis set was defined as all patients registered for this study who received at least one dose of tofacitinib according to the approved Korean label and followed up for safety data. Effectiveness analysis set included patients in the safety analysis set who were evaluated for overall effectiveness assessment and excluded patients who had received tofacitinib less than 8 weeks. RESULTS: A total of 110 patients were enrolled, of whom 106 patients were included in the safety population. The median duration of treatment was 370 days and the treatment duration ranged from 16 to 684 days for the safety population. AEs occurred in 42 patients (39.6%). Serious AEs (SAEs) occurred in 7 patients (6.6%) and of them, there were 2 cases of serious infections. These serious infections were reported as Adverse Event of Special Interest (AESI) in this study and no other AESI were reported. There were no cases of death during the study period. Clinical remission rates were 40.0%, 46.7%, 57.6%, and 55.1% at 8, 16, 24, and 52 weeks, and clinical response rates were 77.8%, 87.9%, 56.6%, and 81.4% at each visit, respectively. Endoscopic mucosal healing rates were 58.7% at 16 weeks and 46.2% at 52 weeks. CONCLUSION: Tofacitinib was effective in Korean patients with moderate to severe active UC and the safety findings were consistent with the known safety profile of tofacitinib. This study confirmed the safety and effectiveness of tofacitinib in Korean patients with moderate to severe active UC in routine clinical settings. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov under the identifier NCT04071405, registered on 28 August 2019.

Venetoclax treatment for chronic lymphocytic leukemia/small lymphocytic leukemia in Japan: post-marketing surveillance.

Venetoclax was approved for relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic leukemia (SLL) in Japan in September 2019; however, clinical data in Japanese patients are limited. This all-case post-marketing surveillance assessed efficacy and safety in Japanese patients with R/R CLL/SLL who started venetoclax treatment between November 2019 and August 2020. Overall, the safety and efficacy analysis sets included 129 and 114 patients, respectively. The overall response rate (ORR) was 57.0%; ORRs were higher in patients with versus without concomitant rituximab (65.4% vs. 54.7%), and in patients with 1 versus ≥ 2 prior lines of therapies (72.5% vs. 44.4%). Adverse events (AEs) were reported in 66.7% of patients (86/129); the most common AEs were neutrophil count decreased (22.5%), white blood cell count decreased (7.8%), and tumor lysis syndrome (TLS; 6.2%). AEs of special interest (TLS, myelosuppression, and infection) were manageable in clinical practice in Japan. Venetoclax is efficacious and safe for R/R CLL/SLL patients in the real-world setting in Japan. ClinicalTrials.gov ID: NCT04198415.

Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database.

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance.

INTRODUCTION: Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. METHODS: This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021. RESULTS: Among 570 patients who participated, 523 (91.75%) were female and the mean ± standard deviation (SD) age was 52.4 ± 14.1 years. At baseline, NMOSD expanded disability status scale mean ± SD was 4.19 ± 2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6 months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean ± SD glucocorticoid dose reduced from 12.28 ± 10.17 mg/day at the index date to 8.11 ± 7.30 mg/day at 6 months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6 months. CONCLUSION: In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000041047.

Long-term safety of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: post-marketing extension surveillance in Japan.

Fabry disease is a rare inherited X-linked metabolic disorder in which deficient alpha-galactosidase A activity causes progressive build-up of globotriaosylceramide (Gb3) and multi-system dysfunction. Following approval of agalsidase alfa for Fabry disease in Japan in 2006, an 8-year all-case post-marketing surveillance (PMS) showed that the treatment was well tolerated and effective for managing disease progression in adult Japanese patients. The present nationwide prospective observational study extended the initial PMS by enrolling patients who continued agalsidase alfa treatment after the initial 8-year period in a 6.5-year extension survey. Patient information from the initial PMS and the extension survey was evaluated as a single data set (observation period: February 2007-September 2021). Of 493 patients in the initial PMS, 129 (45.0% male classic, 6.2% male non-classic, 48.8% female heterozygous phenotype) consented to participate in the extension survey and were included in the analysis. The mean duration of treatment was 9.6 years. A total of 145 adverse drug reactions (ADRs) occurred in 31 patients (24%), and 22 serious ADRs occurred in 12 patients (9.3%). Although serious cardiac, renal, or cerebrovascular adverse events decreased in frequency over time in male patients, serious cardiac events continued to occur in female patients, who showed higher incidence of cardiac complications at baseline. No new safety concerns were identified. Additionally, long-term agalsidase alfa treatment sustained the initial reduction in Gb3 concentrations without increasing the rate of anti-agalsidase antibody positivity. These findings suggest that agalsidase alfa treatment demonstrates continued safety and sustains patients' clinical course over the long term.

Maintenance Intravenous Immunoglobulin Therapy for Chronic Inflammatory Demyelinating Polyneuropathy: 18-Month Post-marketing Surveillance in 103 Patients.

Objective The efficacy of maintenance intravenous immunoglobulin (IVIg) therapy has been established to prevent relapse in chronic inflammatory demyelinating polyneuropathy (CIDP). This prospective post-marketing surveillance study evaluated the treatment duration, efficacy, and safety of maintenance IVIg therapy in Japanese patients with CIDP. Methods Patients were registered between June 2017 and December 2018. After induction of IVIg therapy (0.4 g/kg/day for 5 consecutive days), patients received maintenance IVIg (1.0 g/kg every 3 weeks). The observation period was 18 months. Efficacy in preventing relapse was assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Relapse was defined as a worsening of the INCAT score by ≥1 from baseline. Patients The efficacy population comprised 103 patients (80 with typical CIDP and 23 with CIDP variants). Results During the observation period, 86 (83%) patients were scheduled to continue maintenance IVIg therapy during the observation period, and the relapse rate was 24% (21/86). In the remaining 17 patients who showed continuous remission, maintenance IVIg therapy was stopped (mean, 136 days after the start), and the relapse rate was 24% (4/17). One serious adverse drug reaction of cardiac failure was reported. Conclusion In this post-marketing surveillance, most (83%) patients with CIDP were scheduled to continue maintenance IVIg for 18 months, with a relapse rate of 24%, indicating long-term efficacy. Maintenance IVIg therapy was rarely withdrawn, and the relapse rate after withdrawal was 24%. Further studies are required to determine the optimal maintenance IVIg dose and duration.

Safety evaluation of the trastuzumab biosimilar in Iranian women with HER2-positive breast cancer undergoing adjuvant chemotherapy: a post-marketing surveillance.

BACKGROUND: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). RESEARCH DESIGN AND METHODS: The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. RESULTS: A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. CONCLUSIONS: The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06021379.

Quality of antiretroviral, antimalarial and antituberculosis medicines in Zambia: Findings of routine post-marketing surveillance.

Background: There is growing concern in sub-Saharan Africa that poor-quality antimicrobial medicines may negate management of infectious diseases of public health importance should they fail to meet the set criteria of quality, safety and efficacy. Objectives: The objective was to ascertain the quality of antiretroviral, antimalarial and antituberculosis medicines supplied and available in the public health sector in Zambia. Design: A descriptive cross-sectional study was conducted involving the analysis of data from the continuous routine in-country post-marketing surveillance programme in Zambia that assessed the quality of antiretroviral, antimalarial and antituberculosis medicines supplied to public healthcare facilities between January 2018 and June 2023. Methods: Data were extracted from laboratory quality analysis results from samples collected as part of routine post-marketing surveillance by the Zambia Medicines Regulatory Authority between January 2018 and June 2023. The samples were collected from various levels of the pharmaceutical supply chain across Zambia. Samples were analysed according to their respective pharmacopoeia standards at the Medicines Control Authority of Zimbabwe Quality Control Laboratory, a World Health Organization prequalified laboratory. Data were extracted using a structured Excel database and analysed using Microsoft Excel, and GraphPad Prism Software was used for visualizations. Results: Of the 198 samples, 86 (43.43%) were antiretrovirals, 54 (27.27%) antimalarials and 58 (29.29%) antituberculosis medicines. Of these 198 samples, 171 (86.36%) originated from Asia, 19 (9.60%) Africa and 8 (4.04%) Europe. All sampled medicines met their respective quality specifications with respect to tests, which included appearance, identification, assay, uniformity of mass, weight variation, disintegration, dissolution, pH and specific gravity, giving a compliance rate of 100%. Conclusion: Antiretrovirals, antimalarials and antituberculosis medicines obtained from public healthcare facilities in Zambia through routine post-marketing surveillance met their quality standards. This might positively impact treatment outcomes for HIV/AIDS, malaria and tuberculosis. There is a need for large-scale continuous monitoring of the quality of medicines in order to ensure quality is maintained and substandard products removed from the pharmaceutical supply chain.

Outcomes from testing of antiretroviral, antimalarial and antituberculosis medicines in the Zambian public health facilities to establish if they are of good quality, safe and effective for treatment of HIV, malaria and tuberculosis Why was the study done? Management of diseases require the medicines used are able to treat specific ailments for them to be beneficial to the patient. Bad quality medicines may not be able to treat infections and sometimes may be harmful to the patient taking them. Reports of infections that are resistant to treatment are increasing, partly due to poor-quality medicines. This increasing trend disturbs programmes that aim at eradication of these diseases, and frustrates governments. This study aimed to understand the quality of medicines for diseases that cause a lot of hospital admissions and deaths in Zambia. What did the researchers do? The authors studied results of antiretrovirals, antimalarials and antituberculosis medicines collected across Zambia over a five-and-a-half-year period and tested in a quality control laboratory to understand the quality of these products. Quality of these products can affect treatment outcomes of HIV, malaria and tuberculosis. Knowing the quality of medicines in circulation helps generate evidence for decision-making by medicine regulatory bodies as they protect public health. What did the researchers find? Of the 198 results, the majority (n = 86) were antiretrovirals, followed by antituberculosis medicine (n = 58) and antimalarials (n = 54). All medicines that were tested passed with respect to the tests, giving a compliance rate of 100%. This should give confidence to the public pharmaceutical supply chain, with respect to how they procure their pharmaceuticals and how they are distributed and stored. What do the findings mean? The results show that medicines procured for the public sector in Zambia largely meet their quality requirements. This might positively impact treatment outcomes for HIV/AIDS, malaria and tuberculosis. More similar studies are required to establish a true picture of the quality of these medicines.

Unveiling, Analyzing the Mechanisms of, and Proposing Solutions for Bribery in Japan's Medical Device Sector.

Both public and academic scrutiny of the financial relationships between the medical device industry and the healthcare society occur less frequently than those involving the pharmaceutical industry, and Japan is no exception to these shortcomings. This paper examines the ethical and legal challenges inherent in Japan's medical device industry through the lens of bribery scandals, placing these issues within the broader context of global healthcare corruption. It aims to derive lessons and suggest universal strategies for ethical and legal enhancements. The discussion includes two notable cases: one involving inappropriate transactions between a cancer center and a biliary stent manufacturer, and another concerning a corrupt donation scheme between a medical device company and a university's anesthesiology department, which was found guilty. In our analysis, we also acknowledge the industry's efforts toward compliance and reform to maintain a balanced perspective. The analysis not only highlights the unique culture and structure of the Japanese medical device industry, such as the exploitation of flexible pricing and opaque financial practices but also contrasts these issues with the tightly regulated pharmaceutical industry. This approach reveals both sector-specific challenges and common corruption drivers, enhancing our understanding of why such scandals occur and persist. We propose ethical and compliance-focused business measures such as centralizing donation decisions, limiting the financial independence of marketing divisions, and increasing transparency, alongside adopting mandatory disclosure practices based on successful models from the United States and Europe. By emphasizing integrity and presenting diverse perspectives, this study aims to elevate ethical and legal standards in the medical device industry and improve patient health outcomes worldwide.

Mining of neurological adverse events associated with valbenazine: A post-marketing analysis based on FDA adverse event reporting system.

PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.

Safety of nivolumab monotherapy in five cancer types: pooled analysis of post-marketing surveillance in Japan.

BACKGROUND: Nivolumab has been approved for treating ≥ 10 cancer types. However, there is limited information on the incidence of rare, but potentially serious, treatment-related adverse events (TRAEs), as well as notable TRAEs in patients with certain medical disorders or older patients in Japan. METHODS: We performed pooled analyses of data from published post-marketing surveillance in Japan of nivolumab monotherapy for patients with malignant melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and gastric cancer to determine the frequencies of 20 categories of TRAEs of special interest overall and in patient groups with higher perceived safety risks (history of autoimmune disease, interstitial lung disease, tuberculosis, or hepatitis B/C; patients vaccinated during nivolumab treatment; and older patients [≥ 75 years]). RESULTS: The overall population comprised 7421 patients treated with nivolumab. TRAEs were reported in 49.1% of patients, with grade ≥ 3 TRAEs in 16.7%. Endocrine disorders (14.4%), hepatobiliary disorders (10.9%), and interstitial lung disease (7.0%) were the three most common categories (any grade). The incidences of rare TRAEs with high risk of becoming serious, which occurred in < 1% of patients, were consistent with those in previous reports. The frequencies of TRAEs were not markedly increased in the specified patient groups relative to the overall population. CONCLUSION: To our knowledge, this is the largest study examining the safety of nivolumab-treated patients in real-world clinical practice including rare but potentially serious TRAEs. We found no new signals in the safety of nivolumab among the patient groups relative to the overall population, and no additional safety measures are required in these groups. Trial registration UMIN000048892 (overall analysis), JapicCTI-163272 (melanoma), Japic-163271 (non-small cell lung cancer), JapicCTI-184071 (head and neck cancer), JapicCTI-184070 (gastric cancer), and JapicCTI-184069 (renal cell cancer).

Real-world safety and effectiveness of anamorelin for cancer cachexia: Interim analysis of post-marketing surveillance in Japan.

BACKGROUND: Anamorelin was approved in Japan in 2021 to treat cancer cachexia associated with non-small cell lung, gastric, pancreatic, or colorectal cancers. Post-marketing surveillance is being conducted to evaluate the real-world safety and effectiveness of anamorelin. METHODS: This prospective, observational surveillance registered all patients who started treatment with anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were defined as main safety specifications. Body weight (BW) and appetite were assessed as effectiveness specifications. RESULTS: This analysis was based on data as of January 21, 2023. The safety and effectiveness analysis sets included 6016 and 4511 patients, respectively. Treatment-related adverse events in ≥1% of patients were hyperglycemia (3.9%) and nausea (2.6%). The incidences of hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were 4.8%, 1.2%, and 1.1%, respectively. The mean changes (standard error [SE]) in BW from baseline to weeks 3, 12, 24, and 52 were 0.64 (0.05) kg, 1.19 (0.12) kg, 1.40 (0.21) kg, and 1.42 (0.39) kg, respectively. The mean changes (SE) in Functional Assessment of Anorexia/Cachexia Treatment 5-item Anorexia Symptom Scale total scores from baseline to weeks 3, 12, 24, and 52 were 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), and 5.3 (0.47), respectively, exceeding the clinically meaningful improvement score (2.0 points). CONCLUSION: The overall safety of anamorelin raised no new safety concerns, although continued caution may be required for hyperglycemia and nausea. Improvements in BW and appetite were also observed in real-world clinical settings.