Dermatology and Therapy最新文献

{"title":"Practical Management of the JAK1 Inhibitor Abrocitinib for Atopic Dermatitis in Clinical Practice: Special Safety Considerations.","authors":"Melinda J Gooderham, Marjolein de Bruin-Weller, Stephan Weidinger, Michael J Cork, Lawrence F Eichenfield, Eric L Simpson, Athanasios Tsianakas, Urs Kerkmann, Claire Feeney, William Romero","doi":"10.1007/s13555-024-01200-5","DOIUrl":"10.1007/s13555-024-01200-5","url":null,"abstract":"<p><p>Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit-risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2285-2296"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491260","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":"Development of the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA): A De Novo IGA of Cutaneous Manifestations of Dermatomyositis.","authors":"Stephanie McKee, Jason Xenakis, Harriet Makin, Chris Marshall, Randall Winnette, Rohit Aggarwal, Sarah L Knight","doi":"10.1007/s13555-024-01220-1","DOIUrl":"10.1007/s13555-024-01220-1","url":null,"abstract":"<p><strong>Introduction: </strong>Dermatomyositis (DM) is a rare systemic autoimmune disease characterized by a distinctive debilitating skin rash and skeletal muscle weakness. It is unclear if existing clinical outcome assessment (COA) measures include the concepts of priority to patients and those necessary to fully capture improvements in the active cutaneous manifestations of DM. This study aimed to develop the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA), a de novo IGA, for use in clinical trials of adult DM.</p><p><strong>Methods: </strong>Eight DM clinical experts participated in 60-min qualitative interviews consisting of concept elicitation and cognitive debriefing methodologies. Concept elicitation comprised open-ended questions with follow-up probes to explore clinicians' experiences of treating patients with DM, the impact of symptoms on patients' quality of life, and the severity levels of disease characteristics to explore DM progression. Cognitive debriefing required the clinical experts to perform a review of the CDM-IGA, designed to assess the severity of cutaneous disease activity of DM. After the interviews, a consensus meeting with three clinical experts was held to agree on any outstanding issues relating to the CDM-IGA.</p><p><strong>Results: </strong>The CDM-IGA was iteratively developed using the opinions of nine clinical experts. Feedback provided by all clinicians agreed that erythema was the main active cutaneous manifestation of DM and should be the primary characteristic on the CDM-IGA, split by erythema color and extent. To determine cutaneous disease severity, experts suggested adding a metric called secondary changes, which combined erosion/ulceration and lichenification, which could modify the patient's final score. Three clinical experts suggested that a photo-guide to support assessments of erythema across different skin tones could be beneficial.</p><p><strong>Conclusions: </strong>A novel CDM-IGA was developed for use with adult patients with DM in clinical trials, based on an iterative development process that combined qualitative feedback from clinical experts of DM and importantly adult patients living with DM.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2127-2138"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554391","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":"The Impact of Lebrikizumab on Vaccine-Induced Immune Responses: Results from a Phase 3 Study in Adult Patients with Moderate-to-Severe Atopic Dermatitis.","authors":"Jennifer Soung, Vivian Laquer, Joseph F Merola, Angela Moore, Hany Elmaraghy, Chaoran Hu, Maria Lucia Buziqui Piruzeli, Evangeline Pierce, Esther Garcia Gil, Abel D Jarell","doi":"10.1007/s13555-024-01217-w","DOIUrl":"10.1007/s13555-024-01217-w","url":null,"abstract":"<p><strong>Introduction: </strong>Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD).</p><p><strong>Methods: </strong>ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine.</p><p><strong>Results: </strong>At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001).</p><p><strong>Conclusions: </strong>Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT04626297.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2181-2193"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619549","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":"Biologics Versus JAK Inhibitors. Part II: Risk of Infections. A Narrative Review.","authors":"Miguel Mansilla-Polo, Daniel Morgado-Carrasco","doi":"10.1007/s13555-024-01203-2","DOIUrl":"10.1007/s13555-024-01203-2","url":null,"abstract":"<p><strong>Introduction: </strong>The risk of infections associated with biological drugs (BD) and Janus kinase inhibitors (JAKi) has been extensively explored in the literature. However, there is a dearth of studies that evaluate both pharmacological groups together and, furthermore, compare them. Here, we review the risk of infections associated with BD and JAKi used in dermatology.</p><p><strong>Methods: </strong>A narrative review was performed. All relevant articles evaluating the risk of infection and opportunistic infections with BD and JAKi between January 2010 and February 2024 were selected.</p><p><strong>Results: </strong>Overall, the incidence of infections, serious infections, and opportunistic infections associated with BD and JAKi is low, but higher than in the general population. JAKi approved for dermatological disorders (abrocitinib, baricitinib, deucravacitinib, upadacitinib, ritlecitinib, and topical ruxolitinib) have been shown to be safe, and present a low rate of infections. We found an elevated risk, especially with anti-tumor necrosis factor (anti-TNF) agents, rituximab, and JAKi (particularly tofacitinib at high doses). Specific associations with infections include tuberculosis and tuberculosis reactivation with anti-TNF agents and tocilizumab; candidiasis with anti-interleukin (IL) 17 agents; hepatitis B virus reactivation with rituximab, anti-TNF, and JAKi; and herpes simplex and herpes zoster infections with JAKi (especially tofacitinib and upadacitinib at high doses). The incidence of infections with ustekinumab and anti-IL-23 was very low. Anti-IL-1, nemolizumab, tralokinumab, and omalizumab were not associated with an increased risk of infections. Dupilumab could decrease the incidence of cutaneous infections.</p><p><strong>Conclusions: </strong>Anti-TNF agents, rituximab, and JAKi (particularly tofacitinib) can increase the risk of infections. Close monitoring of patients undergoing these therapies is recommended. Prospective studies with long-term follow-up are needed to comparatively evaluate the risks of infection deriving from treatment with BD and JAKi.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"1983-2038"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626279","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":"How Digital Solutions Might Provide a World of New Opportunities for Holistic and Empathic Support of Patients with Hidradenitis Suppurativa.","authors":"Annie Boucher, Martin Peters, Graham B Jones","doi":"10.1007/s13555-024-01234-9","DOIUrl":"10.1007/s13555-024-01234-9","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a complex chronic relapsing inflammatory condition anchored in the hair follicle wherein painful abscesses, nodules, and tunnels form under the skin with the potential for intermittent pus drainage and tissue scarring. Current estimates of incidence are 1-4% globally with the disease three times more prevalent in women and higher rates among Black populations. Patients with HS are also more likely to suffer from depression, anxiety, and loneliness underscoring the need for carefully approached strategies on disease awareness and interventions. Delays in formal diagnosis, which have been estimated at 7-10 years on average, impede timely provision of optimal care. Despite best intent, when patients present at a physician's office, stigmas relating to physical appearance can be exacerbated by negative interactions experienced by patients. In addition to long wait times and the dearth of available HS expert dermatology professionals, patients perceive heightened physician focus on two of the HS flare risk factors (smoking and body mass index [BMI]) as negatively impacting their care. Given the need for continual, personal, and sensitive patient support, herein we advocate for re-examination of approach to care and the leveraging of highly personalized digital support solutions. New medications which can directly or indirectly control elements of the disease and its comorbidities are also entering the marketplace. Collectively, we posit that these new developments provide opportunity for a holistic approach for patients with HS, leading to long-term engagement and improved outcomes.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"1975-1981"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747694","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":"Deucravacitinib Improves Patient-Reported Outcomes in Patients with Moderate to Severe Psoriasis: Results from the Phase 3 Randomized POETYK PSO-1 and PSO-2 Trials.","authors":"April W Armstrong, Matthias Augustin, Jennifer L Beaumont, Tan P Pham, Stacie Hudgens, Kenneth B Gordon, Joe Zhuo, Brandon Becker, Yichen Zhong, Renata M Kisa, Subhashis Banerjee, Kim A Papp","doi":"10.1007/s13555-024-01224-x","DOIUrl":"10.1007/s13555-024-01224-x","url":null,"abstract":"<p><strong>Introduction: </strong>Deucravacitinib, a novel, oral, selective allosteric tyrosine kinase 2 inhibitor, demonstrated superiority versus placebo and apremilast in the POETYK PSO-1 and PSO-2 studies. We describe patient-reported outcomes with deucravacitinib treatment versus placebo and apremilast in these studies.</p><p><strong>Methods: </strong>Two multicenter, global, double-blind, placebo- and active comparator-controlled studies randomized patients with moderate-to-severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Score changes from baseline and meaningful within-patient change responses for Psoriasis Symptoms and Signs Diary (PSSD) and Dermatology Life Quality Index (DLQI) were assessed.</p><p><strong>Results: </strong>In POETYK PSO-1 (n = 666) and PSO-2 (n = 1020), respectively, improvement from baseline in PSSD total score was greater with deucravacitinib (- 27.8 and - 30.1) versus placebo (- 4.4 and - 5.9) and apremilast (- 18.9 and - 22.5) at Week 16 and versus apremilast at Week 24 (deucravacitinib: - 32.8 and - 30.7; apremilast: - 21.6 and - 22.8) (nominal p < 0.0001). Improvement from baseline in DLQI score was also greater with deucravacitinib (- 8.5 and - 7.6) versus placebo (- 3.3 and - 3.0) and apremilast (- 5.9 and - 5.8) at Week 16 and versus apremilast at Week 24 (deucravacitinib: - 8.6 and - 7.5; apremilast: - 5.6 and - 5.5) (nominal p < 0.0001). Achievement of meaningful within-patient change in PSSD total score and in DLQI score occurred more frequently with deucravacitinib than placebo and apremilast at Week 16 and versus apremilast at Week 24.</p><p><strong>Conclusions: </strong>Deucravacitinib demonstrated meaningful improvements in patient-reported outcomes in patients with moderate-to-severe plaque psoriasis compared with apremilast and placebo.</p><p><strong>Clinical trial registration: </strong>NCT03624127, NCT03611751.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2235-2248"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855124","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":"Psoriasis and Sleep Disturbance: A US Population-Based Study Using the NHANES Database.","authors":"Payton Smith, Joy Q Jin, Riley K Spencer, Kareem G Elhage, Chandler E Johnson, Kathryn Haran, Allison Kranyak, Mitchell S Davis, Marwa Hakimi, Aric A Prather, Katie L Stone, Wilson Liao, Tina Bhutani","doi":"10.1007/s13555-024-01211-2","DOIUrl":"10.1007/s13555-024-01211-2","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis, a chronic inflammatory skin condition, affects approximately 3.0% of the US population, with patients often experiencing significant sleep disturbances. These disturbances include a higher prevalence of conditions such as obstructive sleep apnea, restless leg syndrome, and insomnia. Given the additional risks for cardiovascular disease, metabolic disorders, and depression linked to both poor sleep and psoriasis, addressing sleep issues in this patient group is critical.</p><p><strong>Methods: </strong>The study utilized National Health and Nutrition Examination Survey (NHANES) data, focusing on individuals aged ≥ 20 years who provided information on psoriasis status and sleep. Multistage stratified survey methodology was applied, with multivariable logistic regression models used to examine the association between psoriasis and sleep issues, adjusting for factors such as age, gender, and health history.</p><p><strong>Results: </strong>Psoriasis diagnosis was significantly associated with trouble sleeping (adjusted odds ratio [aOR] 1.88; 95% confidence interval [CI] 1.44-2.45). There was no significant association between psoriasis and sleep quantity. Older age, female gender, and a history of sleep disorders were predictors of trouble sleeping among psoriasis patients.</p><p><strong>Conclusions: </strong>Psoriasis is significantly associated with sleep disturbances, independent of sleep duration. This underscores the need for clinical screening focusing on sleep quality rather than quantity in psoriasis patients to effectively identify and treat sleep-related comorbidities. Further research using objective sleep measures is warranted to guide clinical management and improve patient quality of life.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2277-2283"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466853","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":"Dupilumab in Patients with Atopic Dermatitis: A Multicentric, Long-Term, Real-World Portuguese Study.","authors":"Tiago Torres, Maria João Cruz, Margarida Gonçalo, Paulo Filipe, Bruno Duarte, João Alves, José Miguel Alvarenga, Gilberto Rosa, Duarte Flor, José Ramos, Diogo Sousa, Aureliu Rosca, César Magalhães, Cristina Claro, Joana Rocha, Catarina Vilarinho, Fernando Mota, Alberto Mota, Maria João Paiva Lopes","doi":"10.1007/s13555-024-01235-8","DOIUrl":"10.1007/s13555-024-01235-8","url":null,"abstract":"<p><strong>Introduction: </strong>Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD.</p><p><strong>Methods: </strong>This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI).</p><p><strong>Results: </strong>A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%.</p><p><strong>Conclusions: </strong>This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2209-2221"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747693","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":"Discussion of EMA Draft Guideline on Quality and Equivalence of Topical Products Based on Comparison of Approved Mometasone Furoate Drugs.","authors":"Adina Eichner, Yahya Mrestani, Martin Hukauf, Johannes Wohlrab","doi":"10.1007/s13555-024-01222-z","DOIUrl":"10.1007/s13555-024-01222-z","url":null,"abstract":"<p><strong>Introduction: </strong>Today, the approval for a generic topical product includes the presentation of therapeutic equivalence to the originator based on clinical trials. To facilitate this procedure, in 2018 the European Medicines Agency (EMA) published a draft guideline on quality and equivalence of topical products, which includes request parameters regarding the quality of the newly developed generic product and test protocols for the implementation of equivalence tests regarding efficacy.</p><p><strong>Methods: </strong>To date, no data are available on the quality and evidence of the proposed test conditions. In this study, we performed an in vitro penetration test (IVPT) following the terms of the EMA draft guideline on two authorized topical products for which therapeutic equivalence was already proven during the approval process.</p><p><strong>Results: </strong>The complex biometric data processing revealed that in vitro equivalence could not be observed for all skin sections for either originator or generic product. Moreover, the necessity of the negative control proposed in the draft guideline is more than questionable. From the results presented, there were indications that a reduced number of skin donors would be sufficient to achieve statistically significant equivalence in the comparison of all applied formulations. Here, n = 7 donors was proposed instead of n <math><mo>≥</mo></math> 12 as the EMA draft guideline demands, decreasing the degree of biodiversity simultaneously. Moreover, a higher number of independent replicates (n > 2) was proposed for proper statistics.</p><p><strong>Conclusion: </strong>This bioequivalence study shows insufficient parameters, which should be discussed together with the EMA draft guideline.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2153-2169"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598795","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":"Treatment of Epidermolysis Bullosa and Future Directions: A Review.","authors":"Sorina Danescu, Mircea Negrutiu, Cristina Has","doi":"10.1007/s13555-024-01227-8","DOIUrl":"10.1007/s13555-024-01227-8","url":null,"abstract":"<p><p>Epidermolysis bullosa (EB) comprises rare genetic disorders characterized by skin and mucosal membrane blistering induced by mechanical trauma. Molecularly, pathogenic variants affect genes encoding proteins crucial for epidermal-dermal adhesion and stability. Management of severe EB is multidisciplinary, focusing on wound healing support, ensuring that patients thrive, and complication treatment. Despite extensive research over 30 years, novel therapeutic approaches face challenges. Gene therapy and protein therapy struggle with efficacy, while regenerative cell-based therapies show limited effects. Drug repurposing to target various pathogenic mechanisms has gained attention, as has in vivo gene therapy with drugs for dystrophic and junctional EB that were recently approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). However, their high cost limits global accessibility. This review examines therapeutic advancements made over the past 5 years, exploiting a systematic literature review and clinical trial data.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2059-2075"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874455","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}