Infectious Diseases and Therapy最新文献

{"title":"Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19.","authors":"Dipak R Patel, Lisa Macpherson, Martin Bohm, Himanshu Upadhyaya, Carmen Deveau, Ajay Nirula, Paul Klekotka, Mark Williams, Matthew M Hufford","doi":"10.1007/s40121-024-01031-z","DOIUrl":"10.1007/s40121-024-01031-z","url":null,"abstract":"<p><strong>Introduction: </strong>The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date.</p><p><strong>Methods: </strong>This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion.</p><p><strong>Results: </strong>Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was - 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus - 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported.</p><p><strong>Conclusions: </strong>Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30-60 min.</p><p><strong>Trial registration: </strong>Clinical trial.gov identifier, NCT04427501.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2123-2134"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycoplasma hominis as Cause of Extragenital Infection in Patients with Hypogammaglobulinemia: Report of 2 Cases and Literature Review.","authors":"Chiara Russo, Malgorzata Mikulska, Emanuele Delfino, Federica Toscanini, Laura Mezzogori, Riccardo Schiavoni, Claudia Bartalucci, Emanuele Angelucci, Giulia Bartalucci, Massimiliano Gambella, Anna Maria Raiola, Paola Morici, Francesca Crea, Silvia Chiola, Silvia Daniela Morbelli, Anna Marchese, Matteo Bassetti","doi":"10.1007/s40121-024-01035-9","DOIUrl":"10.1007/s40121-024-01035-9","url":null,"abstract":"<p><p>Mycoplasma hominis can be a part of human urogenital tract microbiome, and it is a frequent cause of urogenital infections. In rare cases, it can also cause extragenital infections, especially in immunocompromised patients. In this case series, we report two cases and provide a literature review of extragenital infections caused by M. hominis in patients with hypogammaglobulinemia. Patient 1 was a 61-year-old woman with diffuse large B-cell lymphoma who, after rituximab-containing chemotherapy and CAR-T therapy, developed M. hominis spondylodiscitis. Patient 2 was a 50-year-old woman with congenital hypogammaglobulinemia who developed disseminated M. hominis infection involving pleura, muscles, and right ankle. Antibiotic therapy with levofloxacin and doxycycline for 10 weeks in patient 1 and with levofloxacin alone for 6 weeks in patient 2 led to infection resolution. The literature review identified 14 additional cases reporting M. hominis extragenital infection in patients with hypogammaglobulinemia. M. hominis should also be suspected as an etiological agent of extragenital infection in patients with B-cell immunodeficiency with a clinical picture of persistent, standard-culture negative infection, particularly with arthritis or abscess formation. Even if M. hominis can grow on standard bacterial medium, in suspected cases molecular methods should be promptly used for correct diagnostic work-up and successful therapy.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2179-2193"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Burden Associated with All Infants in Their First RSV Season in the UK: A Static Model of Universal Immunization with Nirsevimab Against RSV-Related Outcomes.","authors":"Alexia Kieffer, Matthieu Beuvelet, Gerald Moncayo, Mersha Chetty, Aditya Sardesai, Robert Musci, Richard Hudson","doi":"10.1007/s40121-024-01037-7","DOIUrl":"10.1007/s40121-024-01037-7","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory syncytial virus (RSV) leads to significant morbidity in newborn infants in the United Kingdom (UK). Nirsevimab, a long-acting monoclonal antibody, received approval from the European Medicines Agency and has been licensed by the Medicines and Healthcare products Regulatory Agency for preventing RSV lower respiratory tract disease (LRTD) in neonates and infants during their first RSV season. The objective of this study was to assess the potential impact of nirsevimab on RSV-associated LRTDs, related costs, and loss of quality-adjusted life years (QALYs) in infants experiencing their first RSV season.</p><p><strong>Methods: </strong>The impact of administering nirsevimab across all infant populations compared to palivizumab in the high-risk palivizumab-eligible population was assessed via a static decision-analytic model specified for a UK birth cohort experiencing their first RSV season. The RSV-related health events of interest included primary care (PC), accident and emergency (A&E) visits, hospitalizations [including hospitalizations alone and those resulting in intensive care unit (ICU) admissions], recurrent wheezing in infants who were previously hospitalized, and all-cause LRTD hospitalizations.</p><p><strong>Results: </strong>Under the current standard of practice (SoP), RSV was estimated to result in 329,425 RSV LRTDs annually, including 24,381 hospitalizations and ICU admissions, representing £117.8 million (2024 GBP) in costs. Comparatively, universal immunization of all infants with nirsevimab could avoid 198,886 RSV LRTDs, including 16,657 hospitalizations and ICU admissions, resulting in savings of £77.2 million in RSV treatment costs. Considering the impact on all-cause LRTD of a universal immunization strategy, nirsevimab could be valued between £243 and £274, assuming willingness-to-pay (WTP) thresholds of £20,000 and £30,000 per QALY saved, respectively.</p><p><strong>Conclusions: </strong>This analysis demonstrated that the health and economic burden of RSV would be substantially reduced in all infants experiencing their first RSV season in the UK (including term, preterm, and palivizumab-eligible infants) as a result of a universal immunization strategy with nirsevimab.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2135-2153"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to: A Letter to the Editor Regarding 'Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework'.","authors":"Ekkehard Beck, Mary T Bausch-Jurken, Nicolas Van de Velde, Xuan Wang, Mia Malmenäs","doi":"10.1007/s40121-024-01020-2","DOIUrl":"10.1007/s40121-024-01020-2","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2195-2202"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza-Associated Excess Mortality and Hospitalization in Germany from 1996 to 2018","authors":"Christian J. A. Schindler, Ian Wittenberg, Oliver Damm, Rolf Kramer, Rafael Mikolajczyk, Tonio Schönfelder","doi":"10.1007/s40121-024-01043-9","DOIUrl":"https://doi.org/10.1007/s40121-024-01043-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Influenza-associated excess mortality and morbidity is commonly estimated using statistical methods. In Germany, the Robert Koch Institute (RKI) uses the relative mortality distribution method (RMDM) to estimate influenza-associated excess mortality without reporting age-specific values. In order to better differentiate the distribution of the disease burden, a distinction by age is of high relevance. Therefore, we aimed to revise the existing excess mortality model and provide age-specific excess mortality estimates over multiple seasons. We also used the model to determine influenza-associated excess hospitalizations, since the RKI excess hospitalization model is currently based on another approach (i.e., combination of excess physician visits and hospitalized proportion).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study was a retrospective data analysis based on secondary data of the German population from 1996–2018. We adapted the RKI’s method of estimating influenza-associated excess mortality with the RMDM and also applied this approach to excess hospitalizations. We calculated the number of excess deaths/hospitalizations using weekly and age-specific data.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Data available in Germany are suitable for addressing the restrictions of the RKI’s mortality model. In total, we estimated 175,858 (176,482 with age stratification) influenza-associated excess all cause deaths between 1995–1996 and 2017–2018 ranging from 0 (17 with age stratification) in 2005–2006 to 25,599 (25,527 with age stratification) in 2017–2018. Total influenza-associated excess deaths were comparable to RKI’s estimates in most seasons. Most excess deaths/hospitalizations occurred in patients aged ≥ 60 years (95.42%/57.49%) followed by those aged 35–59 years (3,80%/24,98%). Compared with our model, the RKI hospitalization model implies a substantial underestimation of excess hospitalizations (828,090 vs. 374,200 over all seasons).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This is the first study that provides age-specific estimates of influenza-associated excess mortality in Germany. The results clearly show that the main burden of influenza is in the elderly, for whom prevention and control measures should be prioritized.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"69 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding: \"Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults\".","authors":"Hinpetch Daungsupawong,Viroj Wiwanitkit","doi":"10.1007/s40121-024-01038-6","DOIUrl":"https://doi.org/10.1007/s40121-024-01038-6","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"39 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Model-Based Estimation of RSV-Attributable Incidence of Hospitalizations and Deaths in Italy Between 2015 and 2019","authors":"Estelle Méroc, Caihua Liang, Raffaella Iantomasi, Chukwuemeka Onwuchekwa, Giuseppe Pietro Innocenti, Daniela d’Angela, Solomon Molalign, Thao Mai Phuong Tran, Somsuvro Basu, Bradford D. Gessner, Robin Bruyndonckx, Aleksandra Polkowska-Kramek, Elizabeth Begier","doi":"10.1007/s40121-024-01041-x","DOIUrl":"https://doi.org/10.1007/s40121-024-01041-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Respiratory syncytial virus (RSV) incidence is known to be underestimated in adults due to its infrequent diagnostic testing and lower sensitivity of single nasal/nasopharyngeal swab PCR testing outside of the early childhood period. RSV can trigger acute cardiac events as well as cause respiratory disease. Consequently, we used a model-based study to estimate RSV-attributable hospitalization and mortality incidence among adults in Italy between 2015 and 2019.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Through a database predisposed by CREA Sanità, by extracting monthly data from the Italian hospitalization collection data of the Ministry of Health and the Italian National Institute of Statistics (ISTAT) data (mortality), we estimated yearly RSV-attributable incidence of events for different cardiorespiratory outcomes. We used a quasi-Poisson regression model, which accounted for periodic and aperiodic time trends and viral activity proxies.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The yearly RSV-attributable cardiorespiratory hospitalization incidence increased with age and was highest among adults aged ≥ 75 years (1064–1527 cases per 100,000 person-years). Similarly, the RSV-attributable cardiorespiratory mortality rate was highest among persons aged ≥ 75 years (59–85 deaths per 100,000 person-years). Incidence rates for RSV-attributable hospitalizations and RSV-attributable mortality were on average 2–3 times higher for cardiorespiratory than respiratory disease alone. Incidence rate based on RSV-specific ICD codes only were 405–1729 times lower than modeled estimates accounting for untested events.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>RSV causes a substantial disease burden among adults in Italy and contributes to both respiratory and cardiovascular conditions. Our results emphasize the need for effective RSV prevention strategies, particularly among older adults.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"3 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to: Letter to the Editor Regarding \"Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults\".","authors":"Mihaela Georgieva,Tianyu Sun,Ekkehard Beck","doi":"10.1007/s40121-024-01039-5","DOIUrl":"https://doi.org/10.1007/s40121-024-01039-5","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"41 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study","authors":"Yao Yi, Jun Liu, Yingtao Zhang, Biao Zeng, Liling Lin, Caixia Li, Fen Yang, Hailong Zhang, Ruili Xie, Zhuhang Huang, Min Kang, Yawen Jiang","doi":"10.1007/s40121-024-01040-y","DOIUrl":"https://doi.org/10.1007/s40121-024-01040-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a test-negative case–control study using gastroenteritis surveillance data from four cities (2020–2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) − 58.1–85.3%]) for one dose, 37.6% (95% CI − 58.5–75.4%) for two doses, and 64.1% (95% CI 38.0–79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7–60.2%) for one dose, 74.6% (95% CI 35.3–90.0%) for two doses, and 58.8% (95% CI − 217.6–94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI − 144.7–95.6%) for one dose, 74.0% (95% CI − 92.1–96.5%) for two doses, and 86.6% (95% CI 56.8–95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3–77.6%) for one dose, 73.4% (95% CI 11.9–92.0%) for two doses, and − 27.8% (95% CI − 949.7–84.4%) for three doses.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"15 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod","authors":"Sharon A. Riddler, Constance A. Benson, Cynthia Brinson, Steven G. Deeks, Edwin DeJesus, Anthony Mills, Michael F. Para, Moti N. Ramgopal, Yanhui Cai, Yanan Zheng, Liao Zhang, Wendy Jiang, Xiaopeng Liu, Donovan Verrill, Daina Lim, Christiaan R. de Vries, Jeffrey J. Wallin, Elena Vendrame, Devi SenGupta","doi":"10.1007/s40121-024-01034-w","DOIUrl":"https://doi.org/10.1007/s40121-024-01034-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Vesatolimod is a Toll-like receptor-7 (TLR7) agonist in clinical development as part of a combination regimen for human immunodeficiency virus (HIV) cure. Influenza-like symptoms associated with TLR7-mediated immune activation have been reported in clinical trials of vesatolimod. Therefore, a broader understanding of the safety profile of vesatolimod and association with dose and mechanism of action will help inform future clinical studies.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this analysis, data on flu-like adverse events of interest (AEIs) were pooled from eight clinical studies in which 606 participants either received single or multiple doses of vesatolimod (0.3–12 mg; <i>n</i> = 505) or placebo (<i>n</i> = 101). Vesatolimod pharmacokinetics, inflammatory responses, and pharmacodynamics were assessed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The incidence of flu-like AEIs was higher with vesatolimod versus placebo (19% [96/505] vs. 8% [8/101]) and increased with vesatolimod dose and exposure. Most flu-like AEIs with vesatolimod were grade 1 or 2 severity (55% [53 of 96] grade 1; 35% [34 of 96] grade 2) with onset primarily after the first and second dose. Occurrence of flu-like AEIs after doses 1–3 was predictive of reoccurrence after later doses. Dose-dependent elevations of pharmacodynamic biomarkers (interferon-stimulated gene 15, 2′-5′-oligoadenylate synthetase 1, myxovirus resistance-1, interferon-α, interleukin-1 receptor antagonist, interferon-γ-induced protein 10, interferon-inducible T-cell-α chemoattractant) observed in participants with flu-like AEIs suggest a link with vesatolimod mechanism of action.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Flu-like AEIs associated with vesatolimod administration were typically mild but increased with exposure, which may be predicted by the response to initial doses. The data suggest that adaptive clinical monitoring could help maximize pharmacodynamic responses and balance adverse events in future clinical trials of vesatolimod.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":"69 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}