<b>Purpose:</b> Ruxolitinib (Jakafi) is a Janus kinase 1 and 2 small molecule inhibitor that the Food and Drug Administration approved for myelofibrosis and polycythemia vera. It has been expanded to off-label treatment for a variety of dermatologic conditions, with several clinical trials ongoing. A review of available studies and cases of off-label uses was performed to guide clinicians seeking evidence on the efficacy of this Janus kinase inhibitor for dermatologic disorders. <b>Materials and methods:</b> PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term “ruxolitinib,” and results were manually reviewed to identify published data on off-label uses of ruxolitinib. Studies included are structured by quality of evidence available. <b>Results:</b> Ruxolitinib may have utility in the treatment of atopic dermatitis, psoriasis, and vitiligo, with data from open-label and randomized trials supporting efficacy of topical formulations. Evidence of utility for alopecia areata is mixed and differs depending on topical versus oral form. Evidence for numerous other conditions is available through case reports and case series. <b>Conclusions:</b> There is growing evidence supporting potential off-label use of oral and topical ruxolitinib for a wide range of skin conditions. There are several ongoing investigations of ruxolitinib use in dermatology that will undoubtedly better define its efficacy and appropriate use in dermatology.
{"title":"Off-Label Use: Ruxolitinib im Einsatz bei entzündlichen Hauterkrankungen","authors":"Wiebke Sondermann","doi":"10.1159/000523810","DOIUrl":"https://doi.org/10.1159/000523810","url":null,"abstract":"<b>Purpose:</b> Ruxolitinib (Jakafi) is a Janus kinase 1 and 2 small molecule inhibitor that the Food and Drug Administration approved for myelofibrosis and polycythemia vera. It has been expanded to off-label treatment for a variety of dermatologic conditions, with several clinical trials ongoing. A review of available studies and cases of off-label uses was performed to guide clinicians seeking evidence on the efficacy of this Janus kinase inhibitor for dermatologic disorders. <b>Materials and methods:</b> PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term “ruxolitinib,” and results were manually reviewed to identify published data on off-label uses of ruxolitinib. Studies included are structured by quality of evidence available. <b>Results:</b> Ruxolitinib may have utility in the treatment of atopic dermatitis, psoriasis, and vitiligo, with data from open-label and randomized trials supporting efficacy of topical formulations. Evidence of utility for alopecia areata is mixed and differs depending on topical versus oral form. Evidence for numerous other conditions is available through case reports and case series. <b>Conclusions:</b> There is growing evidence supporting potential off-label use of oral and topical ruxolitinib for a wide range of skin conditions. There are several ongoing investigations of ruxolitinib use in dermatology that will undoubtedly better define its efficacy and appropriate use in dermatology.","PeriodicalId":501344,"journal":{"name":"Karger Kompass Dermatologie","volume":"12 1","pages":"64-66"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138522032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<b>Background:</b> Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced – ie, unresectable or metastatic – melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population. <b>Methods:</b> We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1–12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing. <b>Findings:</b> Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n = 56), nivolumab (n = 59), or placebo (n = 52). As of July 2, 2019, at a median follow-up of 28.4 months (IQR 17.7–36.8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12.4 months (95% CI 5.3–33.3) in the nivolumab group and 6.4 months (3.3–9.6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0.23 (97.5% CI 0.12–0.45; p < 0.0001), and for the nivolumab group versus placebo group was 0.56 (0.33–0.94; p = 0.011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61.0–84.9) and at 2 years was 70% (55.1–81.0); in the nivolumab group, 1-year recurrence-free survival was 52% (38.1–63.9) and at 2 years was 42% (28.6–54.5); and in the placebo group, this rate was 32% (19.8–45.3) at 1 year and 14% (5.9–25.7) at 2 years. Treatment-related grade 3–4 adverse events were reported in 71% (95% CI 57–82) of patients in the nivolumab plus ipilimumab group and in 27% (16–40) of those in the nivolumab group. Treatment-related adverse events of any grade l
{"title":"Metastasiertes Melanom: Immuntherapie für Patienten ohne Krankheitsnachweis","authors":"Max Schlaak","doi":"10.1159/000517941","DOIUrl":"https://doi.org/10.1159/000517941","url":null,"abstract":"<b>Background:</b> Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced – ie, unresectable or metastatic – melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population. <b>Methods:</b> We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1–12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing. <b>Findings:</b> Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n = 56), nivolumab (n = 59), or placebo (n = 52). As of July 2, 2019, at a median follow-up of 28.4 months (IQR 17.7–36.8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12.4 months (95% CI 5.3–33.3) in the nivolumab group and 6.4 months (3.3–9.6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0.23 (97.5% CI 0.12–0.45; p &#x3c; 0.0001), and for the nivolumab group versus placebo group was 0.56 (0.33–0.94; p = 0.011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61.0–84.9) and at 2 years was 70% (55.1–81.0); in the nivolumab group, 1-year recurrence-free survival was 52% (38.1–63.9) and at 2 years was 42% (28.6–54.5); and in the placebo group, this rate was 32% (19.8–45.3) at 1 year and 14% (5.9–25.7) at 2 years. Treatment-related grade 3–4 adverse events were reported in 71% (95% CI 57–82) of patients in the nivolumab plus ipilimumab group and in 27% (16–40) of those in the nivolumab group. Treatment-related adverse events of any grade l","PeriodicalId":501344,"journal":{"name":"Karger Kompass Dermatologie","volume":"31 1","pages":"132-133"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138523161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.
{"title":"COVID-19: Risiko für Patienten mit chronisch entzündlichen Erkrankungen?","authors":"Evgenia Makrantonaki","doi":"10.1159/000514081","DOIUrl":"https://doi.org/10.1159/000514081","url":null,"abstract":"COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.","PeriodicalId":501344,"journal":{"name":"Karger Kompass Dermatologie","volume":"51 1","pages":"9-11"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138522038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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