Drug Saf. 2024 Jun;47(6):571-573. doi: 10.1007/s40264-024-01441-5. Epub 2024 May 8.

NO ABSTRACT

PMID:38720115 | DOI:10.1007/s40264-024-01441-5

Clin Rheumatol. 2024 May 8. doi: 10.1007/s10067-024-07000-8. Online ahead of print.

ABSTRACT

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

PMID:38720163 | DOI:10.1007/s10067-024-07000-8

BMJ. 2024 May 7;385:e074892. doi: 10.1136/bmj-2023-074892.

ABSTRACT

Polypharmacy is common in older adults and is associated with adverse drug events, cognitive and functional impairment, increased healthcare costs, and increased risk of frailty, falls, hospitalizations, and mortality. Many barriers exist to deprescribing, but increased efforts have been made to develop and implement deprescribing interventions that overcome them. This narrative review describes intervention components and summarizes findings from published randomized controlled trials that have tested deprescribing interventions in older adults with polypharmacy, as well as reports on ongoing trials, guidelines, and resources that can be used to facilitate deprescribing. Most interventions were medication reviews in primary care settings, and many contained components such as shared decision making and/or a focus on patient care priorities, training for healthcare professionals, patient facing education materials, and involvement of family members, representing great heterogeneity in interventions addressing polypharmacy in older adults. Just over half of study interventions were found to perform better than usual care in at least one of their primary outcomes, and most study interventions were assessed over 12 months or less.

PMID:38719530 | DOI:10.1136/bmj-2023-074892

Drug Ther Bull. 2024 May 6:dtb-2024-000031. doi: 10.1136/dtb.2024.000031. Online ahead of print.

NO ABSTRACT

PMID:38719337 | DOI:10.1136/dtb.2024.000031

Am J Public Health. 2024 Jun;114(6):587-589. doi: 10.2105/AJPH.2024.307673.

NO ABSTRACT

PMID:38718337 | DOI:10.2105/AJPH.2024.307673

JMIR Med Inform. 2024 May 1;12:e50164. doi: 10.2196/50164.

ABSTRACT

BACKGROUND: Tolvaptan is the only US Food and Drug Administration-approved drug to slow the progression of autosomal dominant polycystic kidney disease (ADPKD), but it requires strict clinical monitoring due to potential serious adverse events.

OBJECTIVE: We aimed to share our experience in developing and implementing an electronic health record (EHR)-based application to monitor patients with ADPKD who were initiated on tolvaptan.

METHODS: The application was developed in collaboration with clinical informatics professionals based on our clinical protocol with frequent laboratory test monitoring to detect early drug-related toxicity. The application streamlined the clinical workflow and enabled our nursing team to take appropriate actions in real time to prevent drug-related serious adverse events. We retrospectively analyzed the characteristics of the enrolled patients.

RESULTS: As of September 2022, a total of 214 patients were enrolled in the tolvaptan program across all Mayo Clinic sites. Of these, 126 were enrolled in the Tolvaptan Monitoring Registry application and 88 in the Past Tolvaptan Patients application. The mean age at enrollment was 43.1 (SD 9.9) years. A total of 20 (9.3%) patients developed liver toxicity, but only 5 (2.3%) had to discontinue the drug. The 2 EHR-based applications allowed consolidation of all necessary patient information and real-time data management at the individual or population level. This approach facilitated efficient staff workflow, monitoring of drug-related adverse events, and timely prescription renewal.

CONCLUSIONS: Our study highlights the feasibility of integrating digital applications into the EHR workflow to facilitate efficient and safe care delivery for patients enrolled in a tolvaptan program. This workflow needs further validation but could be extended to other health care systems managing chronic diseases requiring drug monitoring.

PMID:38717378 | DOI:10.2196/50164

J Assoc Physicians India. 2023 Oct;71(10):96-98. doi: 10.59556/japi.71.0309.

ABSTRACT

Statins are drugs for preventing cardiac events in the elderly population. Statins are well tolerated with a lower reported incidence of serious side effects (<0.15%) like myopathy and elevated transaminases [>3× upper limit of normal (ULN)]. Serious adverse effects of statins like statin-associated myopathy range from mild muscle pain to rhabdomyolysis. Drug-induced liver injury (DILI) is another adverse effect of statin use, typically presenting with an acute hepatocellular liver injury pattern as mixed or cholestatic injury. Symptoms usually disappear after 3 months of discontinuation of statins. Some patients require immunosuppression with steroids, intravenous immunoglobulin, or rituximab for management of rhabdomyolysis. DILI can be rapidly reversed by the stoppage of the statins if the enzyme elevation is more than twice the normal. Elderly patients are particularly at increased risk of such adverse effects, emphasizing a need for rational prescription of statins in older adults and close monitoring. We report a case of an elderly presenting with paraparesis and later diagnosed to be a case of statin-induced myositis that significantly improved with prompt management. How to cite this article: Kashyap K, Bisht K, Dhar M, et al. Atorvastatin-induced Myositis and Drug-induced Liver Injury. J Assoc Physicians India 2023;71(10):96-98.

PMID:38716533 | DOI:10.59556/japi.71.0309

Front Public Health. 2024 Apr 23;12:1392180. doi: 10.3389/fpubh.2024.1392180. eCollection 2024.

ABSTRACT

INTRODUCTION: Social media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain.

METHOD: Recognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection.

RESULT: The hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively.

DISCUSSION: This study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.

PMID:38716250 | PMC:PMC11074401 | DOI:10.3389/fpubh.2024.1392180

Int J Crit Illn Inj Sci. 2024 Jan-Mar;14(1):32-36. doi: 10.4103/ijciis.ijciis_57_23. Epub 2024 Mar 27.

ABSTRACT

BACKGROUND: Multiple factors influence the fall risk in end-stage kidney disease. This study aims to investigate how medication factors influence the interpretation of fall risk due to age, gender, and years of dialysis treatment among patients undergoing hemodialysis (HD).

METHODS: A cross-sectional study was carried out in 2023 using the Johns Hopkins Fall Risk Assessment tool. Participants were recruited from the HD unit at a tertiary care academic medical center in Ajman, UAE. Data were analyzed between different ages, genders, and years on HD categories with or without medication factors.

RESULTS: Data were collected and analyzed for 44 patients. The fall risk of the study population assessed with the Kruskal-Wallis test showed no difference between different age groups (P = 0.43) but did show a significant difference when the score of medication factor was removed from the fall risk estimation (P = 0.002). A pairwise analysis showed fall risk score of the age group 46-60 years was differing from the age cohort >60 (P < 0.001). A positive moderate correlation (Spearman's correlation coefficient 0.514 was found, with a P < 0.001) was seen with an increase in age and fall risk only when the medication factor was removed from the fall risk estimation. Results on gender or duration of dialysis were insignificant.

CONCLUSION: Medication factors being a significant contributor to fall risk among the study population was found to mask the fall risk difference between age groups 46-60 years and >60 years. Such influence was not found for gender or duration of dialysis.

PMID:38715751 | PMC:PMC11073637 | DOI:10.4103/ijciis.ijciis_57_23

Ther Adv Drug Saf. 2024 May 6;15:20420986241244585. doi: 10.1177/20420986241244585. eCollection 2024.

ABSTRACT

BACKGROUND: Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention.

OBJECTIVES: To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database.

RESEARCH DESIGN: A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI.

METHODS: FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC).

RESULTS: As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone (n = 47, ROR = 7.79, IC = 2.91), fluvoxamine (n = 29, ROR = 4.69, IC = 2.20), and clomipramine (n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin (n = 3, ROR = 21.46, IC = 3.99), nefazodone (n = 264, ROR = 18.67, IC = 3.84), and maprotiline (n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone (n = 187, ROR = 12.71, IC = 0.48), clomipramine (n = 35, ROR = 2.07, IC = 0.26), and mirtazapine (n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals (n = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine.

CONCLUSION: A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.

PMID:38715707 | PMC:PMC11075604 | DOI:10.1177/20420986241244585

Drug Saf. 2024 Jun;47(6):585-599. doi: 10.1007/s40264-024-01423-7. Epub 2024 May 7.

ABSTRACT

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

PMID:38713347 | DOI:10.1007/s40264-024-01423-7

Drug Saf. 2024 Jun;47(6):575-584. doi: 10.1007/s40264-024-01421-9. Epub 2024 May 7.

ABSTRACT

BACKGROUND AND AIM: Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts.

METHODS: We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting.

RESULTS: Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts.

CONCLUSIONS: The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence.

PMID:38713346 | DOI:10.1007/s40264-024-01421-9

Br J Cancer. 2024 May 7. doi: 10.1038/s41416-024-02701-y. Online ahead of print.

ABSTRACT

BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation.

METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis.

RESULTS: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics.

CONCLUSIONS: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.

PMID:38714747 | DOI:10.1038/s41416-024-02701-y

Gut Liver. 2024 May 7. doi: 10.5009/gnl230494. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: : Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones.

METHODS: : This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated.

RESULTS: : Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890).

CONCLUSIONS: : UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

PMID:38712398 | DOI:10.5009/gnl230494

Cureus. 2024 Apr 6;16(4):e57722. doi: 10.7759/cureus.57722. eCollection 2024 Apr.

ABSTRACT

Urticarial vasculitis (UV) is a type of small-vessel vasculitis, which is rarely associated with anti-tumor necrosis factor (TNF)-alpha medication. We describe a 72-year-old woman with multiple comorbidities on several medications, including an adalimumab biosimilar for Hurley stage II recalcitrant hidradenitis suppurativa (HS), who presented with new-onset severe angioedema and a rash with urticarial wheals that covered most of her body surface area. The diagnosis of drug-induced UV is supported by both the history of adalimumab biosimilar use and the histopathology result. The patient responded successfully to a course of doxycycline administered for three months, which was preceded by corticosteroid dosages, both orally and intravenously, to reduce inflammation. The given case highlights the correlation between a distinct dermatologic autoimmune manifestation and TNF-targeted therapy, demonstrating the importance for dermatologists to be aware of the potential side effects of adalimumab biosimilars in order to manage them effectively.

PMID:38711695 | PMC:PMC11073587 | DOI:10.7759/cureus.57722

J Neurogastroenterol Motil. 2024 May 4. doi: 10.5056/jnm23150. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD.

METHODS: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks.

RESULTS: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study.

CONCLUSION: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

PMID:38710534 | DOI:10.5056/jnm23150

J Natl Cancer Inst. 2024 May 6:djae098. doi: 10.1093/jnci/djae098. Online ahead of print.

ABSTRACT

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating-tumor-DNA (ctDNA)-based molecular response rate.

RESULTS: The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (HR = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity.

CONCLUSION: The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering significantly reduced anemia incidence without any compromise to efficacy.

PMID:38710487 | DOI:10.1093/jnci/djae098

Lancet Oncol. 2024 May 3:S1470-2045(24)00140-2. doi: 10.1016/S1470-2045(24)00140-2. Online ahead of print.

ABSTRACT

BACKGROUND: Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate approved by the US Food and Drug Administration and the European Medicines Agency for HER2-mutant non-small-cell lung cancer. Few treatment options exist for patients with HER2-mutant solid tumours beyond lung cancers. We investigated trastuzumab deruxtecan in metastatic solid tumours with specific activating HER2 mutations.

METHODS: In this open-label, phase 2, basket study done in 29 centres in Asia, Europe, and North America, we investigated trastuzumab deruxtecan (5·4 mg/kg every 3 weeks by intravenous infusion) in patients aged 18 years or older with unresectable or metastatic solid tumours with specific activating HER2 mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and disease progression following previous treatment (previous HER2-targeted therapy was permitted) or with no satisfactory alternative treatment options. The primary endpoint was confirmed objective response rate by independent central review. Anti-tumour activity and safety were analysed in all patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT04639219, and is active but no longer recruiting.

FINDINGS: Between Dec 30, 2020, and Jan 25, 2023, 102 patients (62 [61%] female and 40 [39%] male; median age 66·5 years [IQR 58-72]; 51 [50%] White, two [2%] Black or African American, 38 [37%] Asian, and 11 [11%] did not have race information reported) with solid tumours with activating HER2 mutations received trastuzumab deruxtecan and were included in the anti-tumour activity and safety analyses sets. Patients had a median of three (IQR 2-4) previous treatment regimens. The median duration of follow-up was 8·61 months (IQR 3·71-12·68). The objective response rate by independent central review was 29·4% (95% CI 20·8-39·3; 30 of 102 patients). 52 (51%) patients had a treatment-emergent adverse event of grade 3 or worse; the most common events (in ≥5% of patients) were anaemia (16 [16%]) and neutrophil count decreased (eight [8%]). Drug-related treatment-emergent serious adverse events occurred in ten (10%) patients. Adjudicated drug-related interstitial lung disease or pneumonitis of any grade occurred in 11 patients (11%; three grade 1, five grade 2, one grade 3, and two grade 5); there were two (2%) cases of fatal adjudicated drug-related interstitial lung disease or pneumonitis.

INTERPRETATION: Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations, with no new safety signals. Prespecified HER2 mutations might be targeted by HER2-directed antibody-drug conjugates and our findings support further investigation of trastuzumab deruxtecan in the pan-tumour setting.

FUNDING: AstraZeneca and Daiichi Sankyo.

PMID:38710187 | DOI:10.1016/S1470-2045(24)00140-2

Pharmaceut Med. 2024 May;38(3):251-259. doi: 10.1007/s40290-024-00524-z. Epub 2024 May 6.

ABSTRACT

INTRODUCTION: Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment.

OBJECTIVE: The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria.

METHODS: This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019 to 30th October 2020 and the comparison period was 1st November 2020 to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal-Wallis test was used to test for differences in medians between groups.

RESULTS: Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal-Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App.

CONCLUSION: Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients.

PMID:38705932 | DOI:10.1007/s40290-024-00524-z

Res Social Adm Pharm. 2024 May 1:S1551-7411(24)00155-4. doi: 10.1016/j.sapharm.2024.04.018. Online ahead of print.

ABSTRACT

BACKGROUND: Geriatric Oncology is a specialty where a multidisciplinary approach can address the unmet needs of older adults with cancer. Older adults are at increased risk of adverse drug events (ADE) due to age-related changes in pharmacokinetics and pharmacodynamics, increasing treatment complexity, and medication burden.

OBJECTIVES: To review the literature to determine the incidence of unplanned hospitalisation due to ADE for all medications, both systemic anticancer therapy (SACT) and non-SACT medications.

METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search included the following databases: PubMed, CINAHL, and Embase. A manual search of Scopus was then performed. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, Mixed Methods Appraisal Tool (MMAT) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.

RESULTS: Overall, three studies were included. One observational study reported 19 % of unplanned hospital admissions due to ADE in patients aged ≥70 years with cancer. The first retrospective study reported 24 % of unplanned hospital admissions are due to ADE in patients aged ≥70 years with cancer, and the second retrospective study reported 26 % of patients with metastatic melanoma treated with immune checkpoint inhibitors had an unplanned hospital admission due to an ADE.

CONCLUSION: There is a paucity of studies assessing unplanned hospitalisation due to ADE in older adults with cancer. Future studies are needed and should account for the reporting of potential ADE relative to supportive care, ancillary medications, and indeed chronic medications used to treat long-standing comorbidities.

PMID:38705819 | DOI:10.1016/j.sapharm.2024.04.018