Clinical Drug Investigation最新文献

{"title":"Effectiveness of the Approved Nirmatrelvir/Ritonavir and Molnupiravir Regimens for Treatment of Mild/Moderate Laboratory-Confirmed SARS-CoV-2 Infection in Patients Aged 18-64 Years in Hong Kong: A Population-Based Cohort Study.","authors":"George N Okoli, Yun Lin, Peng Wu, Benjamin J Cowling","doi":"10.1007/s40261-026-01575-7","DOIUrl":"10.1007/s40261-026-01575-7","url":null,"abstract":"<p><strong>Background and objectives: </strong>To better inform clinical and public health decision-making on the use of antiviral drugs for mild/moderate SARS-CoV-2 infection in Hong Kong, we sought to assess effectiveness of the approved nirmatrelvir/ritonavir and molnupiravir treatment regimens.</p><p><strong>Methods: </strong>We conducted a cohort study of patients aged 18-64 years with laboratory-confirmed SARS-CoV-2 infection in Hong Kong between April 2022 and January 2023. We utilised a conditional logistic regression model with a 5-strata propensity score-matched analysis adjusted for potential confounders such as age, sex, SARS-CoV-2 vaccination status, and chronic conditions. The outcomes were disease progression (development/worsening of clinical symptoms/conditions), intensive care unit (ICU) admission among hospitalised persons, and mortality at 28 days (infection-related) and 90 days (all-cause) following the recommended 5-day treatment course commencing within 5 days of symptom onset or laboratory confirmation and excluding persons who had a contraindication for the drugs. Results were expressed as adjusted odds ratios with associated 95% confidence intervals.</p><p><strong>Results: </strong>We included 206,418 individuals, of which 53% were symptomatic at infection confirmation. About 33.3% of the individuals were treated with nirmatrelvir/ritonavir whereas only about 6.1% were treated with molnupiravir. Compared with no treatment, treatment with either nirmatrelvir/ritonavir or molnupiravir was associated with significantly reduced odds of disease progression in patients aged 18-44 years [0.20 (0.09-0.42) and 0.10 (0.04-0.26), respectively] and patients aged 45-64 years [0.14 (0.10-0.20) and 0.19 (0.14-0.25), respectively]. Whereas mostly no significant associations were observed with these drugs for the other outcomes in patients aged 18-44 years, they were associated with significantly reduced odds of the outcomes in patients aged 45-64 years. There was no significant difference in the head-to-head comparison between nirmatrelvir/ritonavir and molnupiravir against all the outcomes in patients aged 18-44 years, and against ICU admission in patients aged 45-64 years, but compared with molnupiravir in those aged 45-64 years, nirmatrelvir/ritonavir was associated with significantly reduced odds of disease progression, SARS-CoV-2 infection-related mortality, and all-cause mortality [0.39 (0.22-0.70), 0.20 (0.10-0.38), and 0.33 (0.21-0.53), respectively]. We made these observations mostly irrespective of symptom status.</p><p><strong>Conclusions: </strong>Nirmatrelvir/ritonavir and molnupiravir treatment regimens seemed effective against clinically relevant outcomes in patients aged 18-64 years with laboratory-confirmed SARS-CoV-2 infection in Hong Kong, particularly in those aged 45-64 years for whom nirmatrelvir/ritonavir seemed better than molnupiravir.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1047-1065"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374684","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":"Desvenlafaxine as a Potential First-Line Treatment for Major Depressive Disorder: A Comprehensive Review and Consensus-Based Clinical Perspective on Efficacy, Safety and Patient Selection Profiles.","authors":"Claudia Carmassi, Christoph U Correll, Javier de Diego-Adeliño, Antonio Vian-Lains, Ciro Oliveira, Alex Schneider-Pérez, Vikas Mohan Sharma","doi":"10.1007/s40261-026-01576-6","DOIUrl":"10.1007/s40261-026-01576-6","url":null,"abstract":"<p><p>Major depressive disorder is a leading cause of disability worldwide, with significant challenges in treatment response, adherence and functional recovery. Despite the availability of numerous antidepressants, a substantial proportion of patients fail to achieve remission with initial therapy, underscoring the need for effective first-line treatment options. Desvenlafaxine, a serotonin-noradrenaline reuptake inhibitor, has demonstrated efficacy and safety in major depressive disorder, while its pharmacokinetic properties result in minimal drug-drug interactions. This narrative review evaluates clinical evidence supporting the use of desvenlafaxine as a first-line treatment and examines patient subgroups that may benefit most from this antidepressant. A comprehensive literature review was conducted to evaluate the evidence on desvenlafaxine in the treatment of major depressive disorder. This was supplemented by clinical insights discussed during a virtual advisory board meeting held on 16 December, 2024, attended by the authors-psychiatrists from Italy, Germany, Spain, Ireland and Portugal-together with representatives from Neuraxpharm, who market desvenlafaxine. The available evidence suggests that desvenlafaxine offers early symptom relief, sustained efficacy across diverse major depressive disorder symptom clusters, and benefits for patients with anhedonia, fatigue, cognitive dysfunction and functional impairment. Its tolerability and safety profile, including a lower risk of weight gain and drug-drug interactions, contributes to its ease of use and improved adherence. Based on the authors' clinical consensus, desvenlafaxine may be particularly suitable for working-age adults, perimenopausal and menopausal women, those with general medical comorbidities or polypharmacy concerns, and individuals requiring an antidepressant with a broad mechanism of action. In addition, its predictable pharmacokinetics make it a practical choice in primary care settings. While most current guidelines typically recommend selective serotonin reuptake inhibitors as first-line treatment, the favourable tolerability profile and efficacy of desvenlafaxine across diverse symptom clusters may support its consideration as a first-line option in select patient populations.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"995-1008"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396197","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":"JAK Inhibitors in Inflammatory Skin Diseases: A 15,427-Patient Systematic Review and Meta-analysis of Clinical Trial and Real-World Outcomes.","authors":"Nada Faheem Zayed, Khaled Seetan, Almu'atasim Khamees, Raghad Yousef Yassin, Saleh A Ba-Shammakh","doi":"10.1007/s40261-026-01583-7","DOIUrl":"10.1007/s40261-026-01583-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Janus kinase (JAK) inhibitors are a new class of medications that are changing how we treat inflammatory skin diseases. Even though these drugs are increasingly being approved for various skin conditions, there is still limited detailed comparison of their effectiveness, safety, and long-term effects across different diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;In this study, we systematically evaluated the use of JAK inhibitors in atopic dermatitis, psoriasis, vitiligo, alopecia areata, and hidradenitis suppurativa across both trial and real-world settings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a systematic review following PRISMA 2020 guidelines and searched major databases for randomized controlled trials (RCTs), open-label extensions, and real-world cohort studies published through May 2025. The main effectiveness outcomes included disease-specific measures: Eczema Area and Severity Index (EASI) for atopic dermatitis, Psoriasis Area and Severity Index (PASI) for psoriasis, Severity of Alopecia Tool (SALT) for alopecia areata, Vitiligo Area Scoring Index (VASI) for vitiligo, and Hidradenitis Suppurativa Clinical Response (HiSCR) for hidradenitis suppurativa. Safety outcomes included rates of adverse events, infections, thromboembolism, and cancer. Patient-centered outcomes included quality of life (DLQI) and pruritus reduction. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0 (RoB 2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We included 68 studies (42 RCTs, 14 open-label extensions, and 12 real-world cohorts) with 15,427 patients across five inflammatory skin diseases. Oral JAK inhibitors demonstrated efficacy across multiple conditions compared with placebo, with EASI-75 response rates ranging from 38 to 73% in atopic dermatitis, PASI-75 rates ranging from 33 to 67% in psoriasis, and SALT-50 rates from 30 to 62% in alopecia areata. Topical JAK inhibitors have proven effective for atopic dermatitis and vitiligo but have shown limited benefit in alopecia areata. Safety profiles were generally similar across drugs, with higher rates of upper respiratory infections (5-14%) and herpes zoster reactivation (1-3%) compared with placebo. Serious adverse events, such as major cardiovascular events, venous thromboembolism, and cancers, were rare but did occur.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;JAK inhibitors demonstrate significant efficacy across several inflammatory skin diseases, with a safety profile that warrants ongoing monitoring, particularly in patients with cardiovascular risk factors. Comparative data suggest that selective JAK1 inhibitors appear to offer the most favorable balance between efficacy and safety for atopic dermatitis, whereas JAK1/2 inhibitors showed numerically higher efficacy for alopecia areata, though this difference did not reach statistical significance. However, the interpretation of long-term safety and comparative effectiveness is constrained by the limited duration of co","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"965-984"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444785","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":"Efficacy, Safety, Quality of Life, and Adherence of Dupilumab in Pediatric Atopic Dermatitis: A Systematic Review.","authors":"Jacob Surma, Jenna Currier, David Doyle, Mackenzy Maddock, Garrett Borgman, Cassandra DeGroat, Sierra Demarinis, Natalie Aguilar, Spencer Williams, Patrick Fakhoury, Robert Stachler","doi":"10.1007/s40261-026-01573-9","DOIUrl":"10.1007/s40261-026-01573-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that disproportionately affects children, often causing significant physical, psychological, and social burdens. While biologic therapies have transformed AD management in adults, pediatric-specific evidence remains limited. Dupilumab, an interleukin (IL)-4 receptor α antagonist that inhibits IL-4 and IL-13 signaling, is currently the only US Food and Drug Administration (FDA)-approved biologic for pediatric AD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To systematically review the efficacy, safety, quality of life, and adherence of dupilumab in children (0-12 years) with moderate-to-severe AD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Embase, and Cochrane Library were searched from inception to August 10, 2024, for studies involving biologic use in pediatric AD. Eligible designs included randomized controlled trials (RCTs), open-label extensions, observational studies, case series, and case reports reporting validated efficacy, safety, quality of life, or adherence outcomes. Risk of bias was assessed using the Mixed Methods Appraisal Tool (MMAT). Results were synthesized narratively, stratified by study design and age group; meta-analysis was not performed due to heterogeneity in study designs, outcome measures, and follow-up durations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 1576 records screened, 20 studies (n= around 1200; age range: 5 months to 12 years) met inclusion criteria. Across study designs, dupilumab produced rapid and sustained improvements in disease severity, with mean Eczema Area and Severity Index (EASI) reductions of 62-92% and high EASI-75 response rates (53-94%) within 16-52 weeks. Quality of life gains were substantial, including large reductions in Children's Dermatology Life Quality Index scores (up to ~89%) and marked sleep improvement. Adverse events were generally mild; conjunctivitis (0-20%) was the most common, with rare herpesvirus infections and injection-site reactions. Laboratory abnormalities including eosinophilia and alkaline phosphatase (ALP) elevation were typically asymptomatic and transient. Adherence was high (≥90% in most cohorts), with low discontinuation rates. Data were synthesized across two developmental age groups where possible: children aged 6 months to 5 years and children aged 6 to 11 years. Some studies reported numerically higher or faster responses in younger children (&lt;6 years), although findings were inconsistent across cohorts and limited by differences in disease duration, dosing, and sample size. The predominantly observational and uncontrolled study designs, heterogeneity in outcome measures and follow-up durations, and small sample sizes in several cohorts limit the certainty of the evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Dupilumab demonstrates robust efficacy, durable benefits,","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"931-964"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344151","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":"Optimizing Amiodarone Maintenance Dose to Minimize N-Desethylamiodarone Accumulation and Pulmonary Toxicity: Insights from Machine Learning and Pharmacokinetic Simulation.","authors":"Minori Teraguchi, Toshiaki Komatsu, Yuto Akamada, Takeru Nabeta, Hidehira Fukaya, Junya Ako, Katsuya Otori","doi":"10.1007/s40261-026-01574-8","DOIUrl":"10.1007/s40261-026-01574-8","url":null,"abstract":"<p><strong>Background and objective: </strong>The accumulation of N-desethylamiodarone (DEA), an active metabolite of amiodarone, is a recognized risk factor for interstitial pneumonia. However, predictors of DEA accumulation, particularly during the initiation phase of amiodarone therapy, remain unclear. We aimed to identify predictors of DEA accumulation using classification and regression tree analysis and to verify their association with interstitial pneumonia in patients receiving amiodarone.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 80 patients who underwent therapeutic drug monitoring of amiodarone and DEA levels at Kitasato University Hospital. Potential risk factors for elevated DEA levels (≥ 0.6 mg/L) were identified using classification and regression tree analysis with 20 variables. To prevent overfitting, strict pruning parameters were implemented (minimum bucket size = 7, maximum depth = 2). N-desethylamiodarone levels were compared between patients with and without interstitial pneumonia, and the findings were validated through Monte Carlo simulations based on published pharmacokinetic models.</p><p><strong>Results: </strong>Elevated DEA levels (≥ 0.6 mg/L) were observed in 23 patients (29%). Classification and regression tree analysis identified treatment duration (cutoff: 47 days) and weight-adjusted dose (cutoff: 2.15 mg/kg/day) as primary determinants of DEA accumulation (accuracy: 0.88; area under the curve: 0.90 [95% confidence interval 0.84-0.95]). Among the five patients who developed interstitial pneumonia, four (80%) exhibited elevated DEA levels, compared to 19 of 75 (25%) patients without interstitial pneumonia (p = 0.022). Pharmacokinetic simulations confirmed that the probability of toxic DEA accumulation increases substantially at doses exceeding 150 mg/day.</p><p><strong>Conclusions: </strong>Treatment duration (≥ 47 days) and weight-adjusted dose (≥ 2.15 mg/kg/day) are significant predictors of DEA accumulation in this cohort of Japanese patients. Elevated DEA levels are significantly associated with the onset of interstitial pneumonia. To minimize the risk of toxicity, taking a maintenance dose of ≤ 100 mg/day (or < 2.15 mg/kg/day, which corresponds to ≤ 100 mg/day for a standard 50-kg patient) and monitoring DEA levels are recommended.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1037-1045"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301298","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":"Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.","authors":"Elahe Orak Sarkani, Sarvenaz Parsa, Sanaz Darash, Zahra Monzavi Chaleshtori, Motahareh Taghizadeh, Sheida Yahyazadeh, Omid Vakili","doi":"10.1007/s40261-026-01579-3","DOIUrl":"10.1007/s40261-026-01579-3","url":null,"abstract":"<p><p>Antipsychotic drugs, long established in the management of psychotic disorders, are increasingly recognized as modulators of autophagy with potential implications for cancer therapy. A growing body of evidence demonstrates that several antipsychotics, such as phenothiazines and penfluridol, can regulate autophagic flux in tumor cells, thereby affecting cell survival, apoptotic signaling, and responsiveness to anticancer treatments. Autophagy is a fundamental homeostatic process that enables tumor cells to meet heightened metabolic demands and adapt to diverse cellular stresses; however, its dysregulation can also facilitate therapeutic resistance. Pharmacological modulation of this pathway by antipsychotics may therefore enhance tumor sensitivity to conventional therapies and contribute to overcoming drug resistance. Importantly, the effects of these agents on autophagy are context dependent, varying with drug class, concentration, and tumor type, and can lead to divergent outcomes in tumor growth and progression. Drawing on accumulating preclinical and emerging clinical evidence, the current review delineates the molecular basis of antipsychotic-autophagy crosstalk and highlights the promise of repurposing these agents as adjunctive strategies in cancer treatment, while underscoring the need for rigorous mechanistic and translational investigations.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1009-1029"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367176","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":"Assessing the Adverse Events of Roflumilast and Tapinarof Use in Pediatric and Young Adult Patients with Atopic Dermatitis: A Systematic Review.","authors":"Anya Ramsamooj, Bethany M Joy, Dave D Manguerra, Valerie A Gerriets","doi":"10.1007/s40261-026-01578-4","DOIUrl":"10.1007/s40261-026-01578-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intensely pruritic episodes and eczematous lesions. This disease is prevalent in up to 25% of children, with about half of these cases persisting into adulthood. This systematic review aims to examine two new topical therapies for AD, roflumilast and tapinarof, and investigate the adverse events  associated with their use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and registered in PROSPERO (CRD420251066719). A search was performed in Scopus, Embase, PubMed, Cochrane Library, and Web of Science on 2 June 2025. Randomized controlled trials were included if they reported adverse event outcomes in pediatric patients with AD after either roflumilast or tapinarof treatment; studies with mixed pediatric and adult patients were eligible for inclusion. Studies were excluded if they lacked roflumilast or tapinarof treatment, did not include pediatric patients with AD, or did not report adverse event outcomes. Risk of bias was assessed using the Cochrane Risk of Bias tool. Adverse events were reported as occurrence (n) and frequency (n/N, %) within pooled studies for the roflumilast and tapinarof groups. Risk ratios (RR) and 95% confidence intervals (CI) comparing treatment with vehicle control were calculated using the Mantel-Haenszel fixed-effect model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Seven studies with a total of 3615 patients with AD using roflumilast (N = 1979), tapinarof (N = 658), or vehicle control (N = 978) were included in the final data extraction and analysis. Analyses included adverse event outcomes for mixed pediatric and adult patients. Three studies assessed once-daily 0.05% or 0.15% roflumilast cream use in patients with a mean age of 19.8 years. Four studies assessed once-daily 0.5% or 1% tapinarof cream use in patients with a mean age of 8.15 years. Both therapies displayed significant risks of treatment-emergent adverse events (TEAE) compared with vehicle controls (roflumilast: RR = 1.46, 95% CI = [1.20-1.77] with p = 0.0001; tapinarof: RR = 1.49, 95% CI = [1.24-1.79], p &lt; 0.0001). Treatment-related TEAEs were significantly increased with roflumilast use (RR = 1.92, 95% CI = [1.15-3.19], p = 0.01), but not tapinarof use (RR = 1.30, 95% CI = [0.89-1.91], p = 0.17). Roflumilast was associated with nondermatologic adverse events, while tapinarof was found to have an association with dermatologic adverse events.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Some limitations include the lack of direct comparative studies, limited data in pediatric and young adult populations, and heterogeneity of reported adverse events. Despite this, roflumilast and tapinarof demonstrate distinct adverse event profiles. Roflumilast was associated with an increased risk of treatment-related and nondermatologic adverse eve","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"985-994"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374668","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":"Altered Busulphan Exposure Associated with Concomitant Omeprazole during Hematopoietic Stem Cell Transplantation Conditioning: A Two-Case Report.","authors":"Ibrahim El-Serafi, Rui He, Ying Zhao, Jonas Mattsson, Moustapha Hassan","doi":"10.1007/s40261-026-01581-9","DOIUrl":"10.1007/s40261-026-01581-9","url":null,"abstract":"<p><strong>Background: </strong>Busulphan is eliminated through glutathione conjugation, forming tetrahydrothiophene, which is subsequently oxidized to tetrahydrothiophene 1-oxide and sulfolane via cytochrome (CYP)-mediated pathways, including CYP2C19 and CYP3A4. Omeprazole is a known inhibitor of CYP2C19 and may interfere with the metabolism of busulphan metabolites, thereby altering systemic busulphan exposure. Given the narrow therapeutic index of busulphan, such interactions may have clinically significant consequences.</p><p><strong>Case presentation: </strong>We describe two adult patients who were diagnosed with acute myeloid leukemia and received oral busulphan (twice daily [b.i.d.]) at a dose of 2 mg/kg for two consecutive days (168 mg and 150 mg, respectively) as part of fludarabine/busulphan conditioning prior to hematopoietic stem cell transplantation. Both patients received concomitant treatment with omeprazole.</p><p><strong>Results: </strong>Unexpectedly elevated busulphan plasma area under the curve (AUC) values were observed following the initial dose despite standard dosing (14.311 and 19.378 mg·h/L, respectively). Dose reduction in one patient did not normalize systemic exposure, whereas discontinuation of omeprazole in the second patient only was followed by a marked decrease in busulphan levels. On the second day, the corresponding AUC values were 19.320 (135%) and 13.772 mg·h/L (71%), respectively.</p><p><strong>Conclusions: </strong>In these cases, a potential drug-drug interaction was observed between omeprazole and busulphan, possibly mediated through inhibition of CYP-dependent metabolism of busulphan metabolites. Concomitant use of omeprazole during busulphan conditioning should be avoided whenever possible. Therapeutic drug monitoring remains essential to optimize busulphan exposure and minimize the risk of treatment-related toxicity.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1031-1036"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419382","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":"Retrospective Real-World Comparison of Adherence, Persistence, Health-Care Utilization, and Costs Among Biologics for Moderate-to-Severe Psoriasis in China.","authors":"Xiaoning He, Xiaoyang Xu, Xingzhi Wang, Jing Wu","doi":"10.1007/s40261-026-01555-x","DOIUrl":"https://doi.org/10.1007/s40261-026-01555-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biologics have significantly enhanced treatment for psoriasis but data regarding their treatment patterns and economic burden are limited. The aim of this study was to evaluate adherence, persistence, switching, health-care resource utilization (HCRU) and costs among secukinumab, adalimumab, ustekinumab, and ixekizumab in China.</p><p><strong>Methods: </strong>This retrospective observational study identified adult patients with psoriasis who initiated biologics between 1 January 2020 and 30 June 2022, from the Regional Medical Big Data of Tianjin, China (comprising hospital information system data from 43 tertiary and 39 secondary hospitals). Treatment adherence was assessed using the Proportion of Days Covered (PDC) and PDC ≥ 80% was defined as adherence. Persistence was defined as continuous use of the index biologic without a gap > 180 days between consecutive prescriptions until end of follow-up. Psoriasis-related and all-cause health-care utilization and direct medical costs (Chinese Yuan, ¥) were assessed over a 1-year follow-up period.</p><p><strong>Results: </strong>A total of 1646 patients (mean age 43.7 ± 14.0 years; 67.0% male) were included of whom 1306, 182, 98, and 60 initiated treatments with secukinumab, adalimumab, ustekinumab, and ixekizumab, respectively. Patient medication adherence decreased over time. At 12 months, ustekinumab and ixekizumab had similar persistence rates (65.9% and 64.7%, P = 0.588), while secukinumab and adalimumab had lower rates (32.3% and 17.9%, respectively, P < 0.001). Only 3.0% of the overall patients switched to second-line therapy. Patients treated with secukinumab and adalimumab more frequently used outpatient services (95.6% and 99.5% visited annually, P < 0.001), while a higher proportion of ustekinumab and ixekizumab patients were hospitalized (81.6% and 83.3%, respectively, P < 0.001). The annual costs were highest for patients initiated with ustekinumab (¥22,727 ± 11,028), followed by secukinumab (¥20,037 ± 13,369), driven by the drug costs of biologics.</p><p><strong>Conclusions: </strong>This study suggests that ustekinumab and ixekizumab are associated with better adherence and persistence compared with secukinumab and adalimumab. Ustekinumab and ixekizumab are primarily used during hospitalization, possibly owing to their high unit price or low injection frequency. Cost-effective treatment options that enhance treatment adherence and persistence are required.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757471","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":"Modeling the Budget Impact of Disease-Modifying Therapies in Infantile-Onset Spinal Muscular Atrophy.","authors":"Sumaya Abuloha, Amie Goodin, Tianze Jiao, Manuela Corti, Mikael Svensson","doi":"10.1007/s40261-026-01571-x","DOIUrl":"10.1007/s40261-026-01571-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Nusinersen, onasemnogene abeparvovec-xioi, and risdiplam are disease-modifying therapies that have demonstrated clinical benefits for patients with spinal muscular atrophy. However, their high costs pose significant challenges for healthcare payers. This study evaluated the potential budget impact of these treatments compared with best supportive care from a US healthcare payer perspective.</p><p><strong>Methods: </strong>A budget impact analysis was conducted over a 5-year time horizon using a state-transition model to estimate direct healthcare costs associated with each disease-modifying therapy and best supportive care in a cohort of children with infantile-onset spinal muscular atrophy. A scenario analysis also assessed the budget impact over a lifetime horizon. Model inputs for transitions and costs were derived from clinical trials, observational registries, and administrative databases.</p><p><strong>Results: </strong>Compared with best supportive care, the added 5-year per-patient budget impact was $2.18 million for onasemnogene abeparvovec-xioi, $1.51 million for nusinersen, and $1.17 million for risdiplam. When modeled over a lifetime horizon, the incremental per-patient budget impact versus best supportive care was $5.86 million for risdiplam, $3.16 million for onasemnogene abeparvovec-xioi, and $3.05 million for nusinersen.</p><p><strong>Conclusions: </strong>Disease-modifying therapies for the management of infantile-onset spinal muscular atrophy have a substantial budget impact on US healthcare payers, primarily driven by high drug acquisition costs. The impact (per year) becomes less pronounced when evaluated over a longer time horizon, with the largest lifetime budget impact observed for risdiplam.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"883-896"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204326","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}