BioDrugs最新文献

{"title":"The PROPER Study: A 48-Week, Pan-European, Real-World Study of Biosimilar SB5 Following Transition from Reference Adalimumab in Patients with Immune-Mediated Inflammatory Disease.","authors":"Ulf Müller-Ladner, Axel Dignass, Karl Gaffney, Deepak Jadon, Marco Matucci-Cerinic, Triana Lobaton, Philippe Carron, Javier P Gisbert, Ira Pande, Maximilian Utzinger, Janet Addison","doi":"10.1007/s40259-023-00616-3","DOIUrl":"10.1007/s40259-023-00616-3","url":null,"abstract":"<p><strong>Background: </strong>The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease.</p><p><strong>Methods: </strong>Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn's disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan-Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline).</p><p><strong>Results: </strong>A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan-Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80-0.90), 0.80 (0.71-0.86), 0.81 (0.74-0.86), and 0.72 (0.67-0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07-11.67), 2.38 (1.11-5.14), and 2.21 (1.54-3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort.</p><p><strong>Conclusions: </strong>With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected.</p><p><strong>Trial registration: </strong>This trial is registered with ClinicalT","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"873-889"},"PeriodicalIF":5.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/d0/40259_2023_Article_616.PMC10581927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with Biologic Drugs in Pediatric Behçet's Disease: A Comprehensive Analysis of the Published Data.","authors":"Ezgi Deniz Batu,&nbsp;Seher Sener,&nbsp;Veysel Cam,&nbsp;Nuray Aktay Ayaz,&nbsp;Seza Ozen","doi":"10.1007/s40259-023-00613-6","DOIUrl":"10.1007/s40259-023-00613-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Behçet's disease (BD) is a variable vessel vasculitis. Biologic drugs are increasingly used in the treatment of BD. We aimed to analyze biologic drug use in the treatment of pediatric BD.</p><p><strong>Methods: </strong>MEDLINE/PubMed and Scopus databases were searched from the inception of these databases until 15 November 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only reports presenting data of pediatric patients with BD (BD diagnosis < 18 years of age) treated with biologic drugs were included. The demographic features, clinical characteristics, and data on treatment were extracted from the included papers.</p><p><strong>Results: </strong>We included 87 articles including 187 pediatric patients with BD treated with biologic drugs (215 biologic treatments). Tumor necrosis factor (TNF)-α inhibitors (176 treatments) were the most frequently used biologic drugs followed by interferons (21 treatments). Other reported biologic treatments were anti-interleukin-1 agents (n = 11), tocilizumab (n = 4), daclizumab (n = 2), and rituximab (n = 1). The most common indication for biologic drug use was ocular involvement (93 treatments) followed by multisystem active disease (29 treatments). Monoclonal TNF-α inhibitors, adalimumab and infliximab, were preferred over etanercept in ocular and gastrointestinal BD. The improvement rates with any TNF-α inhibitor, adalimumab, infliximab, etanercept, and interferons were 78.5%, 86.1%, 63.4%, 87.5%, and 70%; respectively. The organ-specific improvement rate with TNF-α inhibitors was 76.7% and 70% for ocular and gastrointestinal system involvement. Adverse events have been reported for TNF-α inhibitors, interferons, and rituximab. Six of these were severe [TNF-α inhibitors (n = 4); interferons (n = 2)].</p><p><strong>Conclusions: </strong>The presented systematic literature search revealed that TNF-α inhibitors followed by interferons were the most frequently used biologic drugs in pediatric BD. Both group of biologic treatments appeared to be effective and have an acceptable safety profile in pediatric BD. However, controlled studies are required for analyzing indications for biologic treatments in pediatric BD.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"813-828"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Clinical Outcomes of Bevacizumab-awwb Biosimilar versus Bevacizumab Reference Product in Patients with Metastatic Colorectal Cancer.","authors":"Catherine Pham, Fang Niu, Thomas Delate, Gary L Buchschacher, Yan Li, Ekim Ekinci, Kim Le, Rita L Hui","doi":"10.1007/s40259-023-00624-3","DOIUrl":"10.1007/s40259-023-00624-3","url":null,"abstract":"<p><strong>Background: </strong>Bevacizumab-awwb was the first biosimilar approved for cancer treatment in the USA. Limited information is available on the real-world comparative safety and effectiveness of bevacizumab biosimilars, especially for indications granted approval through extrapolation.</p><p><strong>Objective: </strong>To evaluate the real-world outcomes of patients with metastatic colorectal cancer (mCRC) initiated on bevacizumab-awwb versus bevacizumab reference product.</p><p><strong>Patients and methods: </strong>This was an observational, longitudinal cohort study of US adult patients with mCRC from four integrated care delivery systems who were newly initiated on bevacizumab-awwb between 1 July 2019 and 30 March 2020 or bevacizumab reference product between 1 July 2015 and 30 June 2018. Patients were followed until 1 year after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a binary non-inferiority test with lower margin of 10% and adjusted Cox proportional hazards regression analysis to assess all-cause mortality if non-inferiority was met. Secondary outcomes included counts of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events.</p><p><strong>Results: </strong>A total of 1445 patients initiated on either bevacizumab-awwb (n = 239) or bevacizumab reference product (n = 1206) were included in the analysis. The mean overall age was 60 ± 13 years, 46% of patients were female, and 51% were white. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab reference product, respectively (p < 0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p = 0.93). There were no statistically significant differences in secondary outcomes between the study groups.</p><p><strong>Conclusions: </strong>These findings suggest that bevacizumab-awwb is as effective and safe as bevacizumab reference product for the real-world treatment of mCRC.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"891-899"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Yu-Chien Tsao,&nbsp;Ting-Ying Chen,&nbsp;Li-An Wang,&nbsp;Chia-Chun Lee,&nbsp;Wan-Ju Annabelle Lee,&nbsp;Sheng-Min Hsu,&nbsp;Chi-Chun Lai,&nbsp;Shih-Chieh Shao,&nbsp;Jia-Horung Hung,&nbsp;Edward Chia-Cheng Lai","doi":"10.1007/s40259-023-00621-6","DOIUrl":"10.1007/s40259-023-00621-6","url":null,"abstract":"<p><strong>Background: </strong>Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant.</p><p><strong>Objective: </strong>To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method.</p><p><strong>Results: </strong>We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I²: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I²: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I²: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I²: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I²: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I²: 0% for retinal vein occlusion).</p><p><strong>Conclusions: </strong>Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved.</p><p><strong>Systematic review protocol registration: </strong>PROSPERO CRD42021267854.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"843-854"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10542770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do the Outcomes of Clinical Efficacy Trials Matter in Regulatory Decision-Making for Biosimilars?","authors":"Nadine Kirsch-Stefan,&nbsp;Elena Guillen,&nbsp;Niklas Ekman,&nbsp;Sean Barry,&nbsp;Verena Knippel,&nbsp;Sheila Killalea,&nbsp;Martina Weise,&nbsp;Elena Wolff-Holz","doi":"10.1007/s40259-023-00631-4","DOIUrl":"10.1007/s40259-023-00631-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There is an increasing body of evidence supporting a more flexible approach in clinical data requirements for the approval of more complex biosimilar substances such as monoclonal antibodies (mAbs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this paper is to further analyse the role of quality/chemistry, manufacturing and controls (CMC) and clinical data for the conclusion on biosimilarity and the decision on marketing authorisation (MA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the present study, we analysed the MA applications (MAAs) of all 33 mAbs and three fusion proteins evaluated by the European Medicines Agency (EMA) between July 2012 and November 2022 with special emphasis on all submitted rituximab (four products) and trastuzumab (seven products) biosimilar candidates, including withdrawn applications. For the two withdrawn applications, the comparative efficacy trials suggested biosimilarity, but the quality/CMC package was not accepted by EMA. We therefore investigated whether a negative MAA outcome could have been predicted based on the evidence generated in the quality/CMC packages, regardless of clinical trial data. For this purpose, we reviewed the respective European Public Assessment Reports (EPARs) or withdrawal assessment reports, and the first regulatory assessments for all these 36 MAAs (i.e. day 120 of the centralized procedure), which are not publicly available. During EMA review, where significant issues are identified which would preclude a marketing authorisation, these issues are raised as questions to the applicant and are classified as major objections (MO).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In 67% of cases, the outcome of the quality and clinical assessment was the same, i.e. both the quality and clinical assessments either supported approval or did not support approval. In 11% of cases, MO were identified in the quality part of the submission but not in the clinical data. In 22% of cases, MO were raised on the clinical data package but not on the quality data. However, we found no instance where seemingly negative clinical data, including failed efficacy trials, led to a negative overall decision. In each instance, the failure to confirm similar clinical performance in all investigated aspects was eventually viewed as not being related to the biosimilar per se but as being due to imbalances in the trial arms, immaturity of secondary endpoint results, change in the reference product, or even chance findings. Furthermore, when performing an in-depth analysis of the quality and clinical packages of trastuzumab and rituximab biosimilars, we found that in no case were clinical trial data necessary to resolve residual uncertainties regarding the quality part.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The results further support the argument that sufficient evidence for biosimilarity can be obtained from a combination of analytical and functional testing and pharmacokinetic studies which may also generat","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"855-871"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/b1/40259_2023_Article_631.PMC10581956.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients' Perceptions of Biosimilars: A Systematic Review.","authors":"Qiyou Wu,&nbsp;Zhitao Wang,&nbsp;Xin Wang,&nbsp;Hui Yu,&nbsp;Jing Sun","doi":"10.1007/s40259-023-00620-7","DOIUrl":"10.1007/s40259-023-00620-7","url":null,"abstract":"<p><strong>Objective: </strong>To systematically summarize and evaluate the findings of existing studies about patients' perceptions of biosimilars by assessing their attitudes and knowledge.</p><p><strong>Methods: </strong>We conducted a systematic review of published studies concerning patients' perceptions of biosimilars, using databases of China National Knowledge Infrastructure, SinoMed, Web of Science, PubMed, Embase, and Cochrane Library. Two independent reviewers screened a total of 2197 Chinese or English papers published between 1 January 2018, and 1 October 2022. We assessed the quality of the included studies by applying the Joanna Briggs Institute appraisal tools.</p><p><strong>Results: </strong>Forty-three studies were included in the review, with the majority originating from Europe (n = 22) and North America (n = 10). Of these studies, 37 were cross-sectional quantitative studies, three were quasi-experimental studies, and the remaining three were qualitative studies based on semi-structured interviews. The sample sizes of the included studies ranged from 9 to 6554 patients. Twenty-two out of 31 studies investigating patients' acceptance of biosimilars found that most participants expressed satisfaction with treatment using biosimilars. However, doubts about the clinical effects and regulatory approval pathway could negatively influence patients' attitudes. The majority of patients understood the economic advantages of biosimilars; however, some incorrectly connected lower prices with lower quality. Patients generally lacked knowledge about biosimilars. There were 6-51% of participants who were familiar with biosimilars, and 25-58% thought they did not know enough about biosimilars. Physicians, pharmacists, medicines agencies, academia, and patient associations were identified as the main sources of information on biosimilars for patients. Healthcare providers not informing or advising patients about switching may hinder patients from acquiring enough knowledge.</p><p><strong>Conclusions: </strong>The majority of patients expressed satisfaction with treatment using biosimilars, but limited knowledge continued to impede their perceptions. Doubts about the clinical effects and regulatory approval pathway were identified as major factors that negatively influenced patients' attitudes towards biosimilars, while the impact of a price advantage was mixed. It is essential to maintain a focus on educating healthcare professionals about biosimilars, including their clinical outcomes and the regulatory pathway, which equips them to provide comprehensive and informed guidance to patients.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"829-841"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10542768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria Vaccines: Progress to Date.","authors":"Danielle I Stanisic,&nbsp;Michael F Good","doi":"10.1007/s40259-023-00623-4","DOIUrl":"10.1007/s40259-023-00623-4","url":null,"abstract":"<p><p>Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality over the last two decades, it remains a major public health burden in many countries. This underscores the critical need for improved strategies to prevent, treat and control malaria if we are to ultimately progress towards the eradication of this disease. Ideally, this will include the development and deployment of a highly effective malaria vaccine that is able to induce long-lasting protective immunity. There are many malaria vaccine candidates in development, with more than a dozen of these in clinical development. RTS,S/AS01 (also known as Mosquirix) is the most advanced malaria vaccine and was shown to have modest efficacy against clinical malaria in phase III trials in 5- to 17-month-old infants. Following pilot implementation trials, the World Health Organisation has recommended it for use in Africa in young children who are most at risk of infection with P. falciparum, the deadliest of the human malaria parasites. It is well recognised that more effective malaria vaccines are needed. In this review, we discuss malaria vaccine candidates that have progressed into clinical evaluation and highlight the most advanced candidates: Sanaria's irradiated sporozoite vaccine (PfSPZ Vaccine), the chemoattenuated sporozoite vaccine (PfSPZ-CVac), RTS,S/AS01 and the novel malaria vaccine candidate, R21, which displayed promising, high-level efficacy in a recent small phase IIb trial in Africa.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"737-756"},"PeriodicalIF":6.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/3a/40259_2023_Article_623.PMC10581939.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future Evolution of Biosimilar Development by Application of Current Science and Available Evidence: The Developer's Perspective.","authors":"Hillel P Cohen, Matthew Turner, Dorothy McCabe, Gillian R Woollett","doi":"10.1007/s40259-023-00619-0","DOIUrl":"10.1007/s40259-023-00619-0","url":null,"abstract":"<p><p>Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be less sensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"583-593"},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/9e/40259_2023_Article_619.PMC10432323.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10027954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Safety Profile of JAK Inhibitors in Rheumatic Diseases.","authors":"Jasvinder A Singh","doi":"10.1007/s40259-023-00612-7","DOIUrl":"https://doi.org/10.1007/s40259-023-00612-7","url":null,"abstract":"<p><p>Janus kinase inhibitor (JAKi) medications are small-molecule drugs that affect intracellular signal transduction. They are highly effective oral medications that have been approved for the treatment of various rheumatic diseases, with rheumatoid arthritis being a key example of an autoimmune rheumatic disease. JAKi are oral-route medications that are alternatives to injectable biologic therapies, launched in the late 1990s. While most safety concerns with JAKi are similar to the biologics, there are many differences. New data on comparative safety of JAKi versus tumor necrosis factor inhibitors (TNFi) were recently published that led to new black box warnings by the US Food and Drug Administration (FDA) about cardiovascular and cancer risks and a label change for JAKi. This review summarizes the current published data with regards to the safety of JAKi, focused on rheumatic diseases. Specifically, any risk differences between agents or across different indications are discussed, as well as the risk factors for these adverse outcomes.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"625-635"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Use of Monoclonal Antibodies and Antiviral Therapies for Early Treatment of COVID-19 Outpatients in a Real-World Setting: A Nationwide Study from England and Italy.","authors":"Francesco Ciccimarra,&nbsp;Nicoletta Luxi,&nbsp;Chiara Bellitto,&nbsp;Luca L' Abbate,&nbsp;Pasquale De Nardo,&nbsp;Alessia Savoldi,&nbsp;Alison Yeomans,&nbsp;Mariam Molokhia,&nbsp;Evelina Tacconelli,&nbsp;Gianluca Trifirò","doi":"10.1007/s40259-023-00601-w","DOIUrl":"https://doi.org/10.1007/s40259-023-00601-w","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on early treatment of coronavirus disease 2019 (COVID-19) outpatients with newly approved therapies are sparse.</p><p><strong>Aim: </strong>To explore the pattern of use of monoclonal antibodies (mAbs)/antiviral therapies approved for early COVID-19 treatment in non-hospitalized patients from England and Italy from December 2021 to October 2022.</p><p><strong>Methods: </strong>Public national dashboards on weekly mAb/antiviral use and/or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnoses from the Italian Medicines Agency, the Italian National Institute of Health, National Health Service in England and the UK Government were explored. Prevalence of antiviral use in outpatients during the entire study period and every two weeks was calculated, as a whole and by class and compounds. An interrupted time-series (ITS) analysis was carried out to assess the impact of predominant SARS-CoV-2 variants over time on the prevalence of use of mAbs/antivirals in England and Italy.</p><p><strong>Results: </strong>Overall, 77,469 and 195,604 doses of mAbs/antivirals were respectively administered to a total of 10,630,903 (7.3 per 1000) and 18,168,365 (10.8 per 1000) patients diagnosed with SARS-CoV-2 infection in England and Italy. Prevalence of use every two weeks increased from 0.07% to 3.1% in England and 0.9% to 2.3% in Italy during the study period. Regarding individual compounds, sotrovimab (prevalence of use, 1.6%) and nirmatrelvir/ritonavir (1.6%) in England, and nirmatrelvir/ritonavir (1.7%) and molnupiravir (0.5%) in Italy, reported the highest prevalence during a 2-week period. In the ITS analysis, the transition from Delta to Omicron variant predominance was associated with a significant increase in the use of sotrovimab, molnupiravir, remdesivir and nirmatrelvir/ritonavir in both England and Italy, with a reduction of other marketed mAbs. The extent of the increase was higher in England than in Italy for all these drugs except for nirmatrelvir/ritonavir.</p><p><strong>Conclusions: </strong>In this dual nationwide study, the prevalence of use of mAbs/antivirals against SARS-CoV-2 for early outpatients' treatment increased slowly up to 2.0-3.0% of all patients diagnosed with SARS-CoV-2 infection in both England and Italy from December 2021 to October 2022. The trend of individual drug use varied in relation to predominant SARS-CoV-2 variants with some differences across countries. In line with scientific societies' guidelines, nirmatrelvir/ritonavir was the most frequently prescribed antiviral in both countries in the most recent period.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"675-684"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/17/40259_2023_Article_601.PMC10163563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}