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Objective Results Conclusion A post‐marketing surveillance was conducted to evaluate the safety and efficacy of the buprenorphine transdermal patch under actual clinical practice.Of the 3017 patients included in the safety analysis, adverse drug reactions (ADRs) were observed in 1524 (50.5%), the most common being nausea, skin symptoms at the site of application, constipation, and vomiting. The incidences of respiratory depression and withdrawal symptoms were low, and no drug dependence was observed. Among the 2573 patients included in the efficacy analysis, the efficacy (≥2‐point improvement in the numerical rating scale) rate was 74.4%, which was significantly higher in older adults (≥65 y.o) than in younger adults. Discontinuation was mostly caused by ADRs during the early initiation phase.This study demonstrated the safety and efficacy of long‐term administration of buprenorphine transdermal patches, suggesting that pain control is possible over the long term if attention is paid to ADRs in the early stages of administration. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions IgPro20, a subcutaneous immunoglobulin replacement therapy, is approved in Japan for chronic inflammatory demyelinating polyneuropathy (CIDP). This post‐marketing surveillance study characterized real‐world treatment patterns and safety profile of injection site reactions associated with IgPro20 treatment in Japanese patients with CIDP.Patients with CIDP initiating IgPro20 between October 2019 and September 2022 at medical institutions in Japan were followed for 6 months. The primary outcome was the incidence of injection site reactions. Other outcomes included patient clinicodemographic characteristics, IgPro20 treatment status, CIDP‐related concomitant medications and any concurrent therapies.The analysis included 108 patients from 38 sites. CIDP subtypes were typical (61.1%), multifocal acquired demyelinating sensory and motor neuropathy (multifocal; 19.4%), others (14.8%) or unknown (4.6%). Approximately one‐fifth (21.3%) of patients commenced IgPro20 at a dosage of <200 mg/kg, 27.8% at ≥200 to ≤300 mg/kg, 37.0% at >300 to ≤400 mg/kg and 11.1% at >400 mg/kg. Most doses (82.7%) were given at home: 62.0% self‐administered, 11.7% with caregiver and 8.9% with healthcare professional assistance. A total of 55 patients used CIDP‐related concomitant medications, including corticosteroids (35.2%), immunosuppressants (19.4%) or intravenous immunoglobulin G (7.4%). The data also showed that various treatment patterns were used for these combinations. A total of 40 patients (37.0%) experienced injection site reactions, most frequently injection site erythema (21.3%) and injection site swelling (17.6%); one case of ulcer occurred (0.9%). No significant relationship between injection dosage/speed and the incidence of injection site reactions was observed.This study of the use of subcutaneous IgPro20 for CIDP in Japan showed a real‐world safety profile consistent with phase III trial data. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Fingolimod is the first oral sphingosine‐1‐phosphate receptor modulator approved in Japan for multiple sclerosis (MS). A large Japanese observational study of fingolimod in patients with MS was carried out to support its safety and effectiveness in a real‐world setting.This 2‐year, prospective, multicenter, single‐cohort, observational study included all Japanese patients with MS who initiated fingolimod (0.5 mg/day). Safety endpoints included adverse events and adverse drug reactions. Effectiveness endpoints included the annualized relapse rate, Kurtzke's Expanded Disability Status Scale score and physician clinical global impression. All endpoints were analyzed in fingolimod‐naïve patients.Of the 1792 patients who started fingolimod between 28 November 2011 and 31 May 2013, 1624 and 1623 fingolimod‐naïve patients were included in the safety and effectiveness analysis sets, respectively. The most common MS type was relapsing–remitting MS (89.47%). Adverse events, adverse events leading to discontinuation of fingolimod, adverse drug reactions and serious adverse drug reaction incidences were 64.10%, 15.33%, 57.88% and 23.46%, respectively. No new/unexpected safety signals were identified. The annualized relapse rate was 0.97 during the 1 year before baseline, and decreased to 0.22 after treatment. The mean Expanded Disability Status Scale score remained stable throughout treatment, irrespective of the baseline Expanded Disability Status Scale score (≥3 or <3). Physician clinical global impression was classified as ‘effective’ in the majority of patients (70.3%–90.1%) throughout the treatment period.Fingolimod was well tolerated and no new safety concerns were identified in this Japanese 2‐year post‐marketing study. Additionally, fingolimod was effective in preventing MS relapse and physical disability progression in this real‐world population comprising mainly relapsing–remitting MS patients. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • This study provides the latest valbenazine-related neurological safety profiles, and eighteen AEs were identified as new signals. • Neurological AEs most commonly identified for valbenazine were somnolence, tremor, dizziness, drooling, dyskinesia, and balance disorder. • Our findings could potentially prompt improved awareness of valbenazine-related toxicities and help healthcare professionals mitigate the risk of neurological events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract 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.

Abstract 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. Summary 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 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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). [ABSTRACT FROM AUTHOR]

The safety and efficacy of apremilast in psoriatic disease has been demonstrated in clinical trials, including in Japanese patients. This post‐marketing surveillance study was conducted after approval of apremalast in Japan in 2016 to evaluate the safety and effectiveness of the drug in Japanese patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA) in routine clinical practice. Patients (enrolled between September 1, 2017, and August 31, 2019), were observed for 12 months after apremilast treatment initiation or until discontinuation or withdrawal. Safety was assessed by evaluating adverse reactions (ARs) and serious ARs. Effectiveness measures in PsO included the proportion of patients who achieved global improvement and Physician's Global Assessment (PGA) scores of 0/1 and the change from baseline in the Dermatology Life Quality Index (DLQI) after 6 and 12 months treatment. The safety analysis set included 1063 patients (PsO, n = 992; PsA, n = 127). ARs and serious ARs were reported in 29.4% and 0.7% of patients, respectively; most occurred <1 month after apremilast initiation. There were no reports of fatal ARs, serious infections, hypersensitivity, or vasculitis. No new safety signals were identified. Among the key survey items, gastrointestinal disorders were the most common ARs (21.3%). In patients with PsO, after 6 and 12 months of treatment, effectiveness rates of achieving highly effective or effective global improvement of were 90.9% and 93.8%; PGA 0/1 was achieved by 42.7% and 58.1% of patients; mean decrease from baseline in total DLQI score was 4.2 (p < 0.0001) and 5.7 (p < 0.0001), respectively. Effectiveness was evaluated in a small number of patients with PsA for some measures; after 6 and 12 months of treatment, improvements were observed in global improvement effectiveness rates, Disease Activity Score in 28 Joints score, Visual Analog Scale score, and DLQI score. We conclude that orally administered apremilast was well tolerated and effective in Japanese patients with PsO and/or PsA enrolled in this post‐marketing surveillance study. [ABSTRACT FROM AUTHOR]

Nivolumab was approved for relapsed/refractory classic Hodgkin lymphoma (cHL) in Japan in 2016. After its approval, a prospective, non-interventional, observational post-marketing surveillance was initiated to evaluate the safety and effectiveness of nivolumab treatment for up to 12 months in patients with relapsed/refractory cHL. Of 304 registered patients, 288 were included in safety analyses and 282 in effectiveness analyses. There were 191 (66.3%) male patients, median age was 64.0 years, and 54 patients (18.8%) had performance status ≥ 2. Treatment-related adverse events (TRAEs) were reported in 183 (63.5%) patients, with grade 3–5 TRAEs in 86 (29.9%). The most common TRAEs were infusion reaction (14.6%), hepatic function abnormal (5.9%), interstitial lung disease (ILD) (5.6%), and hypothyroidism (5.2%). TRAEs of special interest in ≥ 5% of patients were infusion reaction (15.6%), hepatic failure/hepatic dysfunction/hepatitis/cholangitis sclerosing (13.2%), thyroid dysfunction (9.7%), and ILD (7.3%). In multivariable analyses, prior allogeneic hematopoietic stem cell transplantation was a risk factor for hepatic failure/hepatic dysfunction/hepatitis/cholangitis sclerosing, and prior thyroid gland disorders was a risk factor for thyroid dysfunction. The overall response rate was 61.7%. In conclusion, nivolumab showed a similar safety profile and comparable effectiveness to that reported in clinical trials for relapsed/refractory cHL (CheckMate 205, ONO-4538-15). [ABSTRACT FROM AUTHOR]

Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05–11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82–6.05), and hypotension (ROR = 3.98, 95% CI: 3.44–4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35–17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70–7.18), and dizziness (ROR = 2.56, 95% CI: 1.68–3.90). This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Objectives: An interim analysis of post-marketing surveillance data to assess the safety and effectiveness of sarilumab in Japanese patients with rheumatoid arthritis refractory to previous treatment. Methods: The interim analysis included patients who initiated sarilumab therapy between June 2018 and January 2021. The primary objective of this surveillance was safety. Results: In total, 1036 patients were enrolled and registered by 12 January 2021 (interim cut-off date). Of these, 678 were included in the safety analysis [75.4% female; mean age (± standard deviation) 65.8 ± 13.0 years]. Adverse drug reactions, defined as adverse events classified as possibly or probably related to sarilumab, were reported in 170 patients (incidence: 25.1%), with white blood cell count decreased (4.4%) and neutrophil count decreased (1.6%) most frequently reported. Serious haematologic disorders (3.4%) and serious infections (including tuberculosis) (2.5%) were the most frequently reported priority surveillance items. No malignant tumour was reported. An absolute neutrophil count (ANC) below the minimum standard value did not increase the incidence of serious infections. Conclusions: Sarilumab was well tolerated, and no new safety signals were noted in this analysis. There was no difference in the frequency of serious infections between patients with an ANC below or above normal. [ABSTRACT FROM AUTHOR]

Objectives: This interim report presents the 12‐week results of a post‐marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria. Methods: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. Results: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 μg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135–139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. Conclusions: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12‐week period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The development of a comprehensive regulatory model for medical devices is essential to ensure the safety, efficacy, and quality of medical devices throughout their lifecycle, from design and development to post-market surveillance. This paper outlines a robust framework for such a regulatory model, detailing key components and processes necessary for effective regulation. Methods: The data and literature were collected from various databases including Springer, Science Direct, Taylor and Francis, Wiley, Bentham Science, and websites of different regulatory agencies. The collected data were utilized in the research work to formulate the new regulatory model. Results: Different guidelines represent acceptable regulatory practices for all medical items. There are four risk classification levels of the medical devices (class I–IV, based on the risk level). For every country, the regulatory requirements are different. Global regulations for medical device approval are essential to guaranteeing their quality, safety, efficacy, and performance before they can be put on the market to safeguard, prevent, enhance, and maintain public health. Different classes have different regulatory steps for approval of the devices, which varies from region to region. The World Health Organization’s Department of Essential Health Technologies’ Diagnostic Imaging and Medical Devices team has developed and implemented the Baseline Country Survey on Medical Devices. The proposed model includes the establishment of a clear legislative and regulatory framework, featuring a risk-based classification system aligned with international standards. It emphasizes rigorous pre-market requirements, including design controls, clinical evaluation, quality management systems, and technical documentation. Market authorization processes are described, highlighting pathways such as Premarket Notification (510(k)), Premarket Approval (PMA), and De Novo Classification, supported by thorough scientific review and expert advisory panels. The present study is all about the global requirements of the regulation of the medical devices and it was concluded that overall, a global comprehensive regulatory model for medical devices aims to strike a balance between ensuring patient safety, facilitating innovation, and enabling timely access to life-saving medical technologies around the world. Conclusion: The model advocates for international harmonization and collaboration, promoting regulatory convergence and the adoption of global standards. It also supports innovation through accelerated approval pathways and regulatory sandboxes, alongside continuous improvement driven by regulatory science research and stakeholder engagement. By integrating these elements, the comprehensive regulatory model aims to protect public health while fostering medical device innovation and ensuring global regulatory compatibility.

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.

ABSTRACTThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to urgent actions by innovators, vaccine developers, regulators, and other stakeholders to ensure public access to protective vaccines while maintaining regulatory agency standards. Although development timelines for vaccines against SARS-CoV-2 were much quicker than standard vaccine development timelines, regulatory requirements for efficacy and safety evaluations, including the volume and quality of data collected, were upheld. Rolling review processes supported by sponsors and regulatory authorities enabled rapid assessment of clinical data as well as emergency use authorization. Post-authorization and pharmacovigilance activities enabled the quantity and breadth of post-marketing safety information to quickly exceed that generated from clinical trials. This paper reviews safety and reactogenicity data for the BNT162 vaccine candidates, including BNT162b2 (Comirnaty, Pfizer/BioNTech COVID-19 vaccine) and bivalent variant-adapted BNT162b2 vaccines, from preclinical studies, clinical trials, post-marketing surveillance, and real-world studies, including an unprecedentedly large body of independent evidence.

ABSTRACTThis scoping review examines the role of digital solutions in active, participant-centered surveillance of adverse events following initial release of COVID-19 vaccines. The goals of this paper were to examine the existing literature surrounding digital solutions and technology used for active, participant centered, AEFI surveillance of novel COVID-19 vaccines approved by WHO. This paper also aimed to identify gaps in literature surrounding digital, active, participant centered AEFI surveillance systems and to identify and describe the core components of active, participant centered, digital surveillance systems being used for post-market AEFI surveillance of WHO approved COVID-19 vaccines, with a focus on the digital solutions and technology being used, the type of AEFI detected, and the populations under surveillance. The findings highlight the need for customized surveillance systems based on local contexts and the lessons learned to improve future vaccine monitoring and pandemic preparedness.

The healthcare system benefits from medical devices because they are instruments that can save lives. There are a number of negative effects that these devices have in addition to their therapeutic effects. To control such unfavourable impacts, a strong cohort vigilant system was required. Material caution had been developed as a result of this. Materiovigilance entails monitoring and analysing incidents that occur as a result of the use of medical technology. It not only controls AE but also brings about international harmony.In India, the post-marketing surveillance mechanism for medical devices is less strict than it is for drugs. Materiovigilance entails monitoring unfavourable outcomes brought on by medical devices after they have been marketed. Many nations, including India, have set up their own post-marketing monitoring systems in accordance with WHO guidelines. It is referred to as the Materiovigilance Programme of India in India. (MvPI).Strict monitoring of medical devices is necessary to stop the use of those that don't reach the minimum standards for quality. If necessary, manufacturers or authorised representatives can also pull certain batches of medical devices off the market. Recall is the term used to describe any action taken by a medical device's maker or supplier to remove or withdraw the device from the market or to retrieve the device from anyone to whom it has been given because the device poses a risk to health. A thorough understanding of adverse events related to medical devices will be provided by the comparative research of the materiovigilance programmes in India and the US. Along with existing regulations, adverse event reporting, and guidance materials, the post-market vigilance framework for medical devices was examined. In order to conduct a thorough research, data was collected from various search engines and combined. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. Methods: This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. Results: Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. Conclusions: In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. Study identifier: NCT01932372. [ABSTRACT FROM AUTHOR]

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/ kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies [ABSTRACT FROM AUTHOR]

Simple Summary: In post-irradiated recurrent head and neck cancer (R-HNC), the treatment safety margin is limited by accumulated toxicity. Despite the development of aggressive curative treatment methods, such as reirradiation with photon or particle beam therapy with or without chemotherapy, sufficient clinical outcomes have not been achieved in various prospective trials due to the limitations imposed by toxicity. Boron neutron capture therapy (BNCT), with its selective cell-by-cell dose delivery, may be an effective and safe treatment option for patients with a prior radiotherapy history, as the previous Phase II trial of BNCT in unresectable locally recurrent or locally R-HNC has shown encouraging results. In this study, we analyzed the results of a Japanese nationwide post-marketing surveillance of BNCT for R-HNC conducted under the national health insurance system and found that toxicity was well-tolerated with preferable efficacy. BNCT is suggested to be a promising treatment option in post-irradiated R-HNC. Background: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). Methods: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. Results: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. Conclusions: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting. [ABSTRACT FROM AUTHOR]

Purpose: Nusinersen is an antisense oligonucleotide for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017–August 2025) in all patients in Japan who received intrathecal nusinersen in real-world clinical settings. We report the interim analysis results of safety and effectiveness. Methods: This interim analysis was conducted using data collected from 401 patients whose case report forms were obtained at least once by 30 May 2020. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness. Results: All 401 patients were diagnosed with SMA and were included in the safety and effectiveness analysis (infantile-onset SMA [n = 126, 31.4%], later-onset SMA [n = 275, 68.6%]). The median duration of treatment was 330 days (range 1–823 days). The incidence proportion of AEs was 31.7% (37.3% in infantile-onset SMA and 29.1% in later-onset SMA). The most common AEs were headache (4.5%), pyrexia (4.2%), and pneumonia (3.7%). The incidence proportion of serious AEs was 11.5%. Nusinersen improved motor function scores and was assessed as 'effective' based on CGI-I in 99.7–100% of patients. Conclusions: This interim analysis of the PMS in Japanese patients treated with nusinersen found no new safety concerns, with the type of AEs consistent with the expected safety profile. The benefit–risk balance of nusinersen treatment remains favorable. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to describe the knowledge, attitudes and practices of Adverse Drug Reactions (ADR) reporting among healthcare professionals at Teaching Hospital Karapitiya (THK), a tertiary care hospital in Sri Lanka. Methodology: A descriptive cross-sectional study was conducted at THK. The healthcare professionals working in THK who were available during the study period were invited to the study. A self-administered pre-tested questionnaire was administered to the participants. Respondents were evaluated for their knowledge, attitudes and practices related to ADR reporting. The data were analyzed using SPSS statistical software. Results: Of the total 444 respondents, 31% were doctors and 69% were nurses. The majority of respondents, 90% (n = 400) were aware of the term ADR, while 64.8% (n = 288) could correctly define it. Among the respondents, 30.8% (n = 137) knew about the types of ADR and only 15.5% (n = 70) were able to mention a drug that is banned due to ADR correctly. Among the respondents, only 38.7% (n = 172) were aware of a formal process of reporting ADR and, only 35.3% (n = 157) stated that they had seen the ADR reporting form. Further, only 33.7% (n = 150) respondents have recognized ADR during their clinical practice and only a small proportion 18.2% (n = 81) have ever reported an ADR during their practice. Regarding attitudes toward ADR reporting, overall 84.1 (n = 373) had positive attitudes toward ADR reporting, while 13.54% (n = 60) of them stayed neutral and 2.25% (n = 10) had negative attitudes toward ADR reporting. Conclusions: Although the majority were aware of ADR, the knowledge and practices regarding spontaneous reporting of ADR are inadequate. However, most respondents have shown a positive attitude toward ADR reporting. A sincere and sustained effort should be made by concerned bodies to enhance the healthcare professionals' knowledge, attitudes, and practices regarding ADR reporting. [ABSTRACT FROM AUTHOR]

Public health officials are currently tasked with the role of regulating medicines, both during the approval process and post-market surveillance. While several successes of pharmacovigilance systems exist, pharmacovigilance systems in place are inadequate for protecting the public, as they are slow to show causation. We argue that while pharmacovigilance system were instrumental in the recall of AstraZeneca and Moderna mRNA Covid vaccines for young people during the Covid-19 pandemic, they were inadequate in identifying several clear safety signals which should have led to their withdrawal from the market. Pharmacovigilance systems have much room for improvement, both in terms of data management, accessibility, and use. We propose several guidelines for pharmacovigilance systems to take to improve their efficacy and their ability to protect the public.

Abstract 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.

Abstract Introduction Molnupiravir is an orally available prodrug of N-hydroxycytidine that received special approval for emergency treatment of coronavirus disease 2019 (COVID-19) in Japan in December 2021 and full approval in April 2023. To assess the real-world safety and effectiveness of molnupiravir in Japanese patients with COVID-19, we conducted nationwide post-marketing surveillance to collect data at registered institutions in Japan. Methods The surveillance data were collected from December 27, 2021, to May 2, 2023. All reported adverse events were collected for safety analysis. Adverse drug reactions (ADRs) were assessed by the treating physicians. Effectiveness was assessed by the composite of hospitalization or all-cause death in outpatients and the composite of oxygen/mechanical ventilation initiation or all-cause death in inpatients. The observation period was from molnupiravir initiation through day 29. Results Of 3214 patients enrolled in the survey, 3179 were analyzed for safety. At baseline, 52.31% (1663/3179) of patients were male, the median (range) age was 69.0 (18–107) years, 82.38% (2619/3179) received COVID-19 vaccines, and 95.72% (3043/3179) had risk factors for severe COVID-19 illness. COVID-19 severity at baseline was mild in 86.44% (2748/3179) and moderate I in 10.22% (325/3179). A total of 205 ADRs occurred in 5.50% (175/3179) of patients; ADRs that occurred in > 0.5% of patients were diarrhea (1.86% [59/3179]) and rash (0.69% [22/3179]). Seven serious ADRs were reported in seven patients. In the effectiveness analysis population, the incidence of all-cause death through day 29 was 1.14% (34/2988), and the incidence of death through day 29 related to COVID-19 was 0.40% (12/2988). The cumulative incidence of the composite endpoint was 2.34% (47/2006) in outpatients and 4.60% (38/826) in inpatients. Conclusions This large-scale survey showed that molnupiravir was safe and effective in real-world settings in highly vaccinated Japanese patients with COVID-19, including older patients and those with comorbidities.

Introduction: Molnupiravir is an orally available prodrug of N-hydroxycytidine that received special approval for emergency treatment of coronavirus disease 2019 (COVID-19) in Japan in December 2021 and full approval in April 2023. To assess the real-world safety and effectiveness of molnupiravir in Japanese patients with COVID-19, we conducted nationwide post-marketing surveillance to collect data at registered institutions in Japan. Methods: The surveillance data were collected from December 27, 2021, to May 2, 2023. All reported adverse events were collected for safety analysis. Adverse drug reactions (ADRs) were assessed by the treating physicians. Effectiveness was assessed by the composite of hospitalization or all-cause death in outpatients and the composite of oxygen/mechanical ventilation initiation or all-cause death in inpatients. The observation period was from molnupiravir initiation through day 29. Results: Of 3214 patients enrolled in the survey, 3179 were analyzed for safety. At baseline, 52.31% (1663/3179) of patients were male, the median (range) age was 69.0 (18–107) years, 82.38% (2619/3179) received COVID-19 vaccines, and 95.72% (3043/3179) had risk factors for severe COVID-19 illness. COVID-19 severity at baseline was mild in 86.44% (2748/3179) and moderate I in 10.22% (325/3179). A total of 205 ADRs occurred in 5.50% (175/3179) of patients; ADRs that occurred in > 0.5% of patients were diarrhea (1.86% [59/3179]) and rash (0.69% [22/3179]). Seven serious ADRs were reported in seven patients. In the effectiveness analysis population, the incidence of all-cause death through day 29 was 1.14% (34/2988), and the incidence of death through day 29 related to COVID-19 was 0.40% (12/2988). The cumulative incidence of the composite endpoint was 2.34% (47/2006) in outpatients and 4.60% (38/826) in inpatients. Conclusions: This large-scale survey showed that molnupiravir was safe and effective in real-world settings in highly vaccinated Japanese patients with COVID-19, including older patients and those with comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: This regulatory post‐marketing surveillance (PMS) was organized to identify the safety and effectiveness of ambrisentan in the Korean population. Method: This was an open‐label, multi‐center PMS conducted from 31 institutions in Korea for 6 years from August 2015 to 2021, to evaluate the use of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). Inclusion criteria are Korean subjects with the World Health Organization functional classification (WHO Fc) II or III PAH who are new users or repeated users with ambrisentan (Volibris®) Tablet 5 or 10 mg per day (age >18 years old). Results: A total of 293 cases were analyzed. The overall incidence of adverse events (AE) was 52.22% and adverse drug reactions (ADR) was 10.92%. Severe AEs occurred in 20.82% of patients. However, only 2 subjects (0.68%) reported serious ADR. The difference in AE incidence was statistically significant for concomitant medications other than PAH medications in the safety analysis and the new users (p = 0.0041 and p = 0.0299, respectively) and elderly population in the repeated users (p = 0.0319). Among the long‐term 223 subjects, the WHO Fc II and III were 41.26% and 58.74% before ambrisentan, and changed after treatment to 3.09%, 66.05%, and 30.86% for Fc I/II/III, respectively. 217 of 249 subjects (87.15%) considered their symptoms to have 'improved' after the last administration. Conclusion: In real‐world practice, ambrisentan demonstrated tolerable safety and favorable effectiveness in PAH patients in Korea. Age and concomitant drug use can affect the occurrence of AE. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this article is to assess the safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in routine clinical settings in Korea. Methods: This is a prospective, multi-centre post-marketing surveillance study. Data were prospectively collected within 6 months after the start of tofacitinib therapy. Safety was evaluated based on the presence of adverse events (AEs) observed in patients who received at least one dose of tofacitinib. Effectiveness was assessed according to the proportion of patients who achieved low disease activity and remission, American College of Rheumatology 20 criteria (ACR20), European League Against Rheumatism (EULAR) response, and change of Disease Activity Score in 28 Joints (DAS28). Results: The incidence rates [patients with events per 100 patient-years (PY)] of AEs and serious AEs were 56.92 and 10.69, respectively. Regarding AEs of special interest, the incidence rates were 4.33 per 100 PY for serious infections and infestations, 5.78 per 100 PY for herpes zoster, no event of tuberculosis, 0.29 per 100 PY for malignancy, 0.29 per 100 PY for venous thromboembolism (one event of deep vein thrombosis and no event of pulmonary embolism), 0.87 per 100 PY for major adverse cardiovascular event, and 0.58 per 100 PY for mortality. Moreover, ~40.48% and 21.60% of patients achieved low disease activity and remission of DAS28-erythrocyte sedimentation rate. The EULAR response was classified as good responders with 39.12% in the DAS28-erythrocyte sedimentation rate. Conclusions: The benefit/risk profile of tofacitinib in adult patients with rheumatoid arthritis in routine clinical settings in Korea was similar to long-term clinical trial data. [ABSTRACT FROM AUTHOR]

Abstract Introduction Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of coronavirus disease 2019 (COVID-19) in South Korea in 2021. The Ministry of Food and Drug Safety in South Korea mandate that new medications be re-examined for safety and effectiveness post-approval in at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate the safety and effectiveness of regdanvimab in real-world clinical care. Methods This prospective, multicentre, phase 4 PMS study was conducted between February 2021 and March 2022 in South Korea. Eligible patients were aged ≥ 18 years with confirmed mild COVID-19 at high risk of disease progression or moderate COVID-19. Patients were hospitalised and treated with regdanvimab (40 mg/kg, day 1) and then monitored until discharge, with a follow-up call on day 28. Adverse events (AEs) were documented, and the COVID-19 disease progression rate was used to measure effectiveness. Results Of the 3123 patients with COVID-19 infection identified, 3036 were eligible for inclusion. Approximately 80% and 5% of the eligible patients were diagnosed with COVID-19 during the delta- and omicron-dominant periods, respectively. Median (range) age was 57 (18–95) years, and 50.6% of patients were male. COVID-19 severity was assessed before treatment, and high-risk mild and moderate COVID-19 was diagnosed in 1030 (33.9%) and 2006 (66.1%) patients, respectively. AEs and adverse drug reactions (ADRs) were experienced by 684 (22.5%) and 363 (12.0%) patients, respectively. The most common ADR was increased liver function test (n = 62, 2.0%). Nine (0.3%) patients discontinued regdanvimab due to ADRs. Overall, 378 (12.5%) patients experienced disease progression after regdanvimab infusion, with extended hospitalisation/re-admission (n = 300, 9.9%) as the most common reason. Supplemental oxygen was required by 282 (9.3%) patients. Ten (0.3%) patients required intensive care monitoring and 3 (0.1%) died due to COVID-19. Conclusion This large-scale PMS study demonstrated that regdanvimab was effective against COVID-19 progression and had an acceptable safety profile when used in real-world clinical practice.

Abstract Introduction The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context). Methods Endpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years’ [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10 mg twice daily], modified release [MR] 11 mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14 December 2017 [US approval, IR/MR] to 6 November 2021; RA: 6 November 2012 [US approval, IR] to 6 November 2021; MR approval, 24 February 2016). Results A total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) of exposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4 years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%). Conclusions Tofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation.

Abstract Background This study was conducted to identify factors associated with the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma and to confirm the real-world safety and effectiveness of pembrolizumab in Japanese patients. Methods This multicenter, observational, post-marketing surveillance was conducted over a 1-year observation period starting at pembrolizumab initiation (200-mg pembrolizumab every 3 weeks); data were collected from case report forms (3 months and 1 year). Safety measures included treatment-related adverse events and adverse events of special interest (AEOSI). Effectiveness assessments included tumor response, objective response rate (ORR), and disease control rate (DCR). Results Overall, 1293 patients were evaluated for safety and 1136 for effectiveness. At 12 months, the treatment-related adverse event incidence was 53.8% (n = 696) and that of AEOSI was 25.0% (n = 323). The most frequent AEOSI of any grade were endocrinological disorder (10.4%, n = 134), interstitial lung disease (ILD) (7.2%, n = 93), and hepatic function disorder (4.9%, n = 64). Multivariate analysis demonstrated that the risk of developing ILD was almost seven times greater (odds ratio 6.60) in patients with a comorbidity of ILD, and approximately twice as high in patients aged ≥ 65 years (odds ratio 2.24) and with smoking history (odds ratio 1.79). The ORR was 26.1% and the DCR was 50.7%. The ORR was 46.4% in patients with a Bellmunt risk score of 0 and decreased as the Bellmunt risk score increased. Conclusions This post-marketing surveillance confirmed the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma in the real-world setting.

Abstract Background The CARD trial was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who had received docetaxel and experienced disease progression within 1 year on an androgen receptor-axis-targeted therapy (ARAT). Subsequent treatment with cabazitaxel had improved clinical outcomes compared with an alternative ARAT. This study aims to confirm the effectiveness of cabazitaxel in real-world patients in Japan and compare their characteristics with those of patients from the CARD trial. Methods This was a post-hoc analysis of a nationwide post-marketing surveillance registering all patients who were prescribed cabazitaxel in Japan between September 2014 and June 2015. Included patients had received docetaxel and ≤ 1 year of an ARAT (abiraterone or enzalutamide) prior to receiving cabazitaxel or an alternative ARAT, as their third-line therapy. The primary effectiveness endpoint was the time to treatment failure (TTF) of the third-line therapy. Patients were matched (1:1) from the cabazitaxel and second ARAT arms based on propensity score (PS). Results Of the 535 patients analysed, 247 received cabazitaxel and 288 the alternative ARAT as their third-line therapy, of which, 91.3% (n = 263/288) received abiraterone and 8.7% (n = 25/288) received enzalutamide as their second third-line ARAT. Patients in the cabazitaxel and second ARAT arms had TNM classification of M1 or MX in 73.3% and 68.1%, Gleason score of 8–10 in 78.5% and 79.2% and mean (standard deviation) serum PSA levels of 483 (1370) and 594 (1241) ng/mL, respectively. Initial cabazitaxel dose was ≤ 20 mg/m2 in 61.9% (n = 153/247) of the patients in the cabazitaxel arm. The median TTF (95% confidence interval [CI]) of the third-line therapy was 109 (94–128) days for cabazitaxel and 58 (57–66) days for the second ARAT, with a hazard ratio (95% CI) of 0.339 (0.279–0.413) favouring cabazitaxel. Similar results were obtained after PS-matching, with a hazard ratio (95% CI) of 0.323 (95% CI 0.258–0.402) favouring cabazitaxel. Conclusions Consistent with the CARD trial, cabazitaxel demonstrated superior effectiveness over a second alternative ARAT in a real-world patient population in Japan, despite the population having more advanced disease status and a lower dose of cabazitaxel being more frequently administered, than in the CARD trial.

Abstract Objectives Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in Japan. Dupilumab, a fully human monoclonal antibody, targets a shared subunit of the interleukin (IL)‐4 and IL‐13 receptors. Post‐marketing surveillance of the safety and effectiveness of dupilumab in adult AD patients was conducted in Japan, where the drug is also allowed for use in older adolescents (i.e., ≥15 years), and interim results are reported here. Methods This observational, multicenter study enrolled Japanese patients with AD who initiated dupilumab between July 2018–June 2020 (UMIN‐CTR Trials Registry: UMIN000032807). Baseline demographics, clinical history, medication data and dupilumab safety and effectiveness data were collected. Results By the data cut‐off date of March 26, 2021, information from 600 patients has been collected. All the available safety and 1‐year effectiveness data are presented. The mean (standard deviation) age was 42.0 (15.9) years, the majority (69.1%) were male, and asthma was present in 12.2%. Adverse drug reactions (ADRs) were observed in 98 patients (16.4%), including conjunctivitis (n = 40; 6.7%), conjunctivitis allergic (n = 30; 5.0%), blepharitis (n = 5; 0.8%), headache and eye pruritus (n = 4; 0.7% each) and eosinophilia (n = 3; 0.5%). Six patients experienced asthma, all of whom had a history of, or concurrent, asthma. Disease severity improved remarkably at 4 months in most patients, which was maintained up to 1 year. Conclusion Dupilumab appears to be a safe and effective treatment for patients aged ≥15 years with moderate‐to‐severe AD in routine clinical practice in Japan. Dupilumab was well tolerated, with no new safety signals and no new‐onset asthma.