Clinical Drug Investigation最新文献

{"title":"Efficacy and Safety of Topical Roflumilast for the Treatment of Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Rafaela de Moraes-Souza, Regina Chahine Chater, Izabela Pera Calvi, Yasmin Mesquita, Rubiana Sarto, Izadora Lapenda, Lívia Figueiredo Pereira, Luana Moury, Pedro Herranz-Pinto","doi":"10.1007/s40261-024-01368-w","DOIUrl":"10.1007/s40261-024-01368-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Plaque psoriasis is commonly treated topically with glucocorticoids and vitamin D derivatives. However, potential side effects such as skin atrophy underscore the need for safe and effective alternative topical therapies. Recently, the US Food and Drug Administration (FDA) and Health Canada approved roflumilast 0.3% cream as an option for treating this disease. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical roflumilast 0.3% compared with vehicle for plaque psoriasis.</p><p><strong>Methods: </strong>PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched from inception to 1 May 2024, assessing the outcomes of Investigator's Global Assessment (IGA) or body-IGA success (clear or almost clear status plus an at least 2-grade improvement from baseline), Psoriasis Area and Severity Index (PASI)-50, PASI-75, PASI-90, intertriginous-IGA success (clear or almost clear status on the intertriginous-IGA plus an at least 2-grade improvement from baseline), and adverse events (AEs). Statistical analysis was performed using Review Manager, R software, and RStudio. Heterogeneity was determined using the Cochran Q test and I² statistics.</p><p><strong>Results: </strong>Four RCTs were included, comprising a total of 1403 patients, of whom 885 (63.1%) received topical roflumilast 0.3% and 518 (36.9%) received vehicle. At week 8, the achievement of IGA or body-IGA success was significantly higher among those treated with topical roflumilast than in the vehicle group [relative risk (RR) 5.07; 95% confidence interval (CI) 3.55-7.23; p < 0.01]. Similar findings were observed at week 8 for PASI-50 (RR 2.73; 95% CI 2.27-3.29; p < 0.01), PASI-75 (RR 4.48; 95% CI 2.26-8.89; p < 0.01), and PASI-90 (RR 5.61; 95% CI 2.57-12.25; p < 0.01). Corresponding outcomes were found at weeks 2, 4, and 6. Additionally, a higher percentage of patients treated with topical roflumilast 0.3% once daily achieved intertriginous-IGA success, compared with those receiving vehicle, at week 8 (71.9% versus 20.5%; RR 3.32; 95% CI 2.11-5.22; p < 0.01), with similar findings at weeks 2, 4, and 6. While a significant difference was observed in the overall incidence of AEs between the topical roflumilast and vehicle groups, there was no difference in treatment-related AEs, serious AEs, or AEs leading to study discontinuation.</p><p><strong>Conclusion: </strong>These findings support the superiority of topical roflumilast 0.3% over vehicle and suggest its use as a valuable asset for the treatment of plaque psoriasis.</p><p><strong>Protocol registration: </strong>International Prospective Register of Systematic Reviews (PROSPERO), CRD42023456494.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"655-665"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016511","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":"Cost-Effectiveness Analysis of Newborn Screening for Spinal Muscular Atrophy in Italy.","authors":"Gianni Ghetti, Francesco Saverio Mennini, Andrea Marcellusi, Matthias Bischof, Gabriele Maria Pistillo, Marika Pane","doi":"10.1007/s40261-024-01386-8","DOIUrl":"10.1007/s40261-024-01386-8","url":null,"abstract":"<p><p>BACKGROUND AND OBJECTIVE: Untreated spinal muscular atrophy (SMA) is the leading genetic cause of death in children younger than 2 years of age. Early detection through newborn screening allows for presymptomatic diagnosis and treatment of SMA. With effective treatments available and reimbursed by the National Health Service, many regions in Italy are implementing newborn screening for SMA. We evaluated the cost effectiveness of universal newborn screening for SMA in Italy.</p><p><strong>Methods: </strong>A decision-analytic model assessed the cost effectiveness of newborn screening from the National Health Service perspective in 400,000 newborns. Newborn screening enabling early identification and presymptomatic treatment of SMA was compared with no newborn screening, symptomatic diagnosis, and treatment. Transition probabilities between health states were estimated from clinical trial data. Higher-functioning health states were associated with increased survival, higher utility values, and lower costs. Long-term survival and utilities were extrapolated from scientific literature. Health care costs were collected from official Italian sources. A lifetime time horizon was applied, and costs and outcomes were discounted at an annual rate of 3%. Deterministic and probabilistic sensitivity analyses were conducted.</p><p><strong>Results: </strong>Newborn screening followed by presymptomatic treatment yielded 324 incremental life-years, 390 incremental quality-adjusted life-years, and reduced costs by €1,513,375 over a lifetime time horizon compared with no newborn screening. Thus, newborn screening was less costly and more effective than no newborn screening. Newborn screening has a 100% probability of being cost effective, assuming a willingness-to-pay threshold of > €40,000.</p><p><strong>Conclusions: </strong>Newborn screening followed by presymptomatic SMA treatment is cost effective from the Italian National Health Service perspective.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"687-701"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016510","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":"Disability and Adverse Effects of Oral Versus Long-Acting Injectable Antipsychotics in Schizophrenia-Spectrum and Bipolar Disorder: A Comparison Based on Data-Driven Taxonomy.","authors":"Alessandro Rodolico, Sofia Francesca Aprile, Pierfelice Cutrufelli, Gabriele Privitera, Sabrina Castellano, Carmen Concerto, Rosaria Furnari, Claudia Savia Guerrera, Ludovico Mineo, Giuseppe Alessio Platania, Antonino Petralia, Filippo Caraci, Maria Salvina Signorelli","doi":"10.1007/s40261-024-01391-x","DOIUrl":"10.1007/s40261-024-01391-x","url":null,"abstract":"<p><strong>Background: </strong>Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications.</p><p><strong>Objectives: </strong>The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy.</p><p><strong>Methods: </strong>This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales.</p><p><strong>Results: </strong>The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean 45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ = 0.475; p < 0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p = 0.014), autonomic (p = 0.008), other (p = 0.004), and sexual adverse effects (p = 0.008), as well as the UKU total score (p = 0.002). The Kruskal-Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p = 0.043).</p><p><strong>Conclusion: </strong>These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"715-727"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281358","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":"Risk of Congenital Anomalies with Dolutegravir-Based Anti-retroviral Regimens: A Systematic Review and Meta-analysis.","authors":"Shuvasree Payra, Divya Harsha, Keshav Kumar, Pramod Kumar Manjhi, Shruti Singh, Rajesh Kumar, Sunil Kumar Singh, Alok Kumar, Vikas Maharshi","doi":"10.1007/s40261-024-01390-y","DOIUrl":"10.1007/s40261-024-01390-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Dolutegravir has been used as a first-line anti-human immunodeficiency virus drug because of its better efficacy compared with other counterpart medicines. However, making a unanimous decision on its use during pregnancy has become difficult for stakeholders following congenital anomalies reported with its use. The objective of this systematic review and meta-analysis was to study the risk of congenital anomalies in newborns exposed to dolutegravir-based-regimens compared with those exposed to non-dolutegravir-based regimens during the antenatal period.</p><p><strong>Methods: </strong>An extensive literature search was performed in MEDLINE (through PubMed), EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, and ClinicalTrials.gov until 30 November, 2023. Studies reporting data on congenital anomalies following antenatal use of dolutegravir were included. Risk of bias for randomized controlled trials, non-randomized controlled trials, and observational studies was assessed using RoB2, ROBINS-I, and ROBINS-E tools, respectively. A meta-analysis was performed in 'RevMan 5.4.1' using a random-effects model. Heterogeneity was assessed by the 'Q' statistic and I² value. A sensitivity analysis was performed for higher heterogeneity/high-risk studies. The study protocol was registered in PROSPERO [CRD42023446374] a priori.</p><p><strong>Results: </strong>Of 26 eligible studies, 12 (six randomized controlled trials and six observational studies with a pooled sample of 32,617) were included in a meta-analysis and 14 in a qualitative synthesis only. The meta-analysis does not show a statistically significant difference in the risk of congenital anomalies between newborns exposed antenatally to dolutegravir-based regimen(s) and those exposed to non-dolutegravir-based regimens [risk ratio 1.10; 95% confidence interval 0.79-1.53; p = 0.59]. Heterogeneity was moderate (I² = 47%). Pooled results for randomized controlled trials and observational studies separately and the sensitivity analysis for heterogeneity provided similar results.</p><p><strong>Conclusions: </strong>The risk of congenital anomalies was not significantly different between dolutegravir-based regimens and non-dolutegravir-based-regimens in newborns exposed during their antenatal period.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"667-685"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281370","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":"Pharmacokinetics and Pharmacodynamics of Nipocalimab, a Neonatal Fc Receptor Blocker, in Healthy Japanese Volunteers.","authors":"Nobuko Matsushima, Sayori Shibata, Jocelyn H Leu, An Vermeulen, Jay Duffner, Leona E Ling, Lisa B Schwartz, Hideo Harigae","doi":"10.1007/s40261-024-01380-0","DOIUrl":"10.1007/s40261-024-01380-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Nipocalimab is a high-affinity, fully human, effectorless immunoglobulin G1 monoclonal antibody targeting the neonatal Fc receptor and is currently under evaluation for the treatment of rare and prevalent immunoglobulin G autoantibody-mediated and alloantibody-mediated diseases. This phase I, randomized, double-blind, placebo-controlled, single-dose escalation study in healthy Japanese volunteers (N = 24) assessed the safety, pharmacokinetics, and effect on the serum immunoglobulin G level of single doses of nipocalimab.</p><p><strong>Methods: </strong>Volunteers were grouped into three cohorts and received intravenous nipocalimab at 10, 30, or 60 mg/kg or placebo. To complement the study, genetic variation in the Fcγ receptor and transporter subunit of the neonatal Fc receptor was analyzed in Japanese and diverse populations.</p><p><strong>Results: </strong>Nipocalimab was generally safe and well tolerated at all dose levels, with three (12.5% [3/24]) volunteers experiencing treatment-emergent adverse events across all nipocalimab doses. Mean serum immunoglobulin G levels decreased in a dose-dependent manner from baseline with nipocalimab treatment compared with placebo. Maximum serum nipocalimab concentrations demonstrated proportional increases with dose, while the area under the concentration-time curve was dose dependent and demonstrated non-linear increases with dose. Mean observed half-life was longer as the dose increased. Analysis of genetic variation in Fcγ receptor and transporter identified no unique Japanese variants or variants that alter amino acid sequences in or near the neonatal Fc receptor immunoglobulin G binding site targeted by nipocalimab.</p><p><strong>Conclusions: </strong>The comparable pharmacokinetic/pharmacodynamic profiles and highly conserved neonatal Fc receptor structure among diverse populations further support the clinical development of nipocalimab for the treatment of various immunoglobulin G autoantibody-mediated and alloantibody-mediated diseases across global sites and populations, including the Japanese population.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"587-599"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787435","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":"Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer.","authors":"Edurne Arriola, Javier de Castro, Rosario García-Campelo, Beatriz Bernárdez, Reyes Bernabé, Jordi Bruna, Manuel Dómine, Dolores Isla, Óscar Juan-Vidal, Teresa López-Fernández, Ernest Nadal, Delvys Rodríguez-Abreu, María Vares, Úrsula Asensio, Luis F García, Enriqueta Felip","doi":"10.1007/s40261-024-01379-7","DOIUrl":"10.1007/s40261-024-01379-7","url":null,"abstract":"<p><p>The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"553-576"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859215","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":"Effectiveness and Safety of Upadacitinib for Adolescents with Atopic Dermatitis in a Real-World Setting.","authors":"Cataldo Patruno, Giuseppe Lauletta, Elena Pezzolo, Valeria Boccaletti, Mariateresa Rossi, Francesca Caroppo, Anna Belloni Fortina, Filomena Russo, Barbara Cocuroccia, Giacomo Dal Bello, Fabrizio Martora, Francesca di Vico, Maddalena Napolitano","doi":"10.1007/s40261-024-01382-y","DOIUrl":"10.1007/s40261-024-01382-y","url":null,"abstract":"<p><strong>Background and objective: </strong>The estimated prevalence of atopic dermatitis (AD) among adolescents (12-17 years of age) is about 14.8%. AD compromises sleep quality and may be associated with poor scholastic performance, mood disruptions, low self-esteem, and difficulty in building social relationships. Upadacitinib was recently approved by the European Medicines Agency for the treatment of moderate-to-severe AD in patients aged ≥ 12 years who are candidates for systemic treatment. The aim of this real-world study was to determine the effectiveness in disease control and safety of upadacitinib in adolescents aged 12-17 years with moderate-to-severe AD.</p><p><strong>Methods: </strong>This is a retrospective study in adolescents with moderate-to-severe AD treated with upadacitinib 15 mg between July 2022 and February 2024 at six Italian dermatological referral centres. The primary endpoint was to analyse the evolution of the response in terms of absolute Eczema Area and Severity Index (EASI) value, as well as the percentage of patients achieving 75% and 90% improvement in EASI (EASI75 and EASI90) from baseline to weeks (W) 4, 16, 24, and 52. Secondary endpoints included the assessment of treatment efficacy in terms of Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), Children's Dermatology Life Quality Index (c-DLQI), and safety.</p><p><strong>Results: </strong>Thirty-six patients [males: 18 (50%)] were evaluated. A statistically significant improvement of EASI was observed at each timepoint, as stated by a mean percentage reduction from baseline of 72.2% at W4, 82.7% at W16, of 86.4% at W24 (n = 34) and of 92.7% at W52 (n = 18) (p < 0.0001). At W4, 21/36 (58.3%) achieved EASI75 and 12/36 (33.3%) EASI90. At W16, 29/36 (80.5%) achieved EASI75 and 19/36 (52.8%) EASI90. At W24, 32/34 (94.1%) reached EASI75 and 24/34 (70.6%) EASI90. Finally, at W52 all the assessed patients (n = 18) maintained EASI75 and 14/18 (77.7%) reached EASI90. Likewise, a statistically significant reduction of c-DLQI, P-NRS and S-NRS was observed at each timepoint.</p><p><strong>Conclusion: </strong>Our real-world experience seems to confirm the efficacy and safety of upadacitinib for the long-term treatment of moderate-to-severe AD in adolescents.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"629-634"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619501","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":"Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.","authors":"Martina Paoletti, Chiara Bini, Andrea Marcellusi, Francesco Saverio Mennini","doi":"10.1007/s40261-024-01366-y","DOIUrl":"10.1007/s40261-024-01366-y","url":null,"abstract":"<p><strong>Background and objective: </strong>In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma.</p><p><strong>Methods: </strong>Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded.</p><p><strong>Results: </strong>For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided.</p><p><strong>Conclusions: </strong>The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"601-609"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901140","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":"Budget Impact of Disease-Modifying Treatments and a CRISPR Gene-Edited Therapy for Sickle Cell Disease.","authors":"Khadidja Abdallah, Isabelle Huys, Kathleen J Claes, Steven Simoens","doi":"10.1007/s40261-024-01384-w","DOIUrl":"10.1007/s40261-024-01384-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Treatment of sickle cell disease (SCD) has traditionally focused on symptomatic and preventative care. Recent advances in novel therapeutic developments, likely to be orphan-designated, are anticipated to carry a substantial price tag. This study assesses the potential budget impact of adopting disease-modifying treatments, crizanlizumab and voxelotor, and pioneering CRISPR gene-edited therapy, CTX001, in the Belgian healthcare system.</p><p><strong>Methods: </strong>The perspective of the Belgian healthcare payer (RIZIV-INAMI including patient copayments), a 5-year horizon with a 2-10% uptake of disease-modifying interventions, and a 2% uptake of CTX001 were considered. Data, encompassing target population, current (chronic and acute management, curative hematopoietic stem cell transplantation) and new (crizanlizumab, voxelotor, and CTX001) interventions, clinical effectiveness, adverse events, healthcare resource utilization, and associated costs, were gathered through a comprehensive literature review (first phase) and two Delphi panels involving hematologists (second phase). The cost difference between a \"world with and without crizanlizumab, voxelotor, and CTX001\" was calculated to obtain the budget impact. Three scenario analyses were conducted: a 5-13% and 4% uptake analysis, a 10-18% and 8% uptake analysis, respectively for disease-modifying treatments (crizanlizumab and voxelotor) and CTX001, and a 0% crizanlizumab uptake and managed entry agreements analysis . A ± 20% univariate sensitivity analysis was performed to test the robustness of the analysis.</p><p><strong>Results: </strong>The total five-year cumulative budget impact was estimated at €30,024,968, with 91% attributed to drug acquisition costs. The largest budget impact share was for CTX001 (€25,575,150), while crizanlizumab (€2,301,095) and voxelotor (€2,148,723) was relatively small. In scenarios one and three, a two-fold increase of the cumulative budget impact to €60,731,772 and a four-fold increase to €120,846,256 from the base case was observed. In scenario three, this budget impact decreased by 63% to €11,212,766. Patient population size, number of treated patients, and drug costs influenced the analysis the most, while discontinuation, acute crisis, and adverse event rates had comparatively minimal impact.</p><p><strong>Conclusions: </strong>Belgian decision-makers may consider alternative financing models, such as outcome-based risk-sharing agreements or annuities, to ensure sustainable coverage of these treatments. This study adheres to recommended practices for assessing budget impact of orphan drugs, distinguishing it from earlier studies with potentially weaker methodologies.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"611-627"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970799","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":"The Early Access and the Potential Cost Savings by the Compassionate Use of Onco-haematological Drugs: Results from the Italian Study Compass-O.","authors":"Irene Dell'Anno, Leonardo Dondi, Immacolata Esposito, Annamaria Mascolo, Annalisa Capuano, Giulia de Marchi, Adriano Cristinziano, Domenico Tarantino, Marcello Pani, Carla Masini, Caterina Donati, Elisabetta Rossin, Antonio Serafini, Gabriele Bagaglini, Gabriella Bonanni, Tommaso Gregori, Arturo Cavaliere, Roberta Matocci, Alessandro D'Arpino, Nello Martini, Carlo Piccinni","doi":"10.1007/s40261-024-01381-z","DOIUrl":"10.1007/s40261-024-01381-z","url":null,"abstract":"<p><strong>Background: </strong>Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021.</p><p><strong>Objective: </strong>We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021.</p><p><strong>Methods: </strong>The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments.</p><p><strong>Results: </strong>Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069.</p><p><strong>Conclusions: </strong>The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"577-586"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731051","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}