Brett King, Jennifer Soung, Christos Tziotzios, Lidia Rudnicka, Pascal Joly, Melinda Gooderham, Rodney Sinclair, Natasha A. Mesinkovska, Carle Paul, Yankun Gong, Susan D. Anway, Helen Tran, Robert Wolk, Samuel H. Zwillich, Alexandre Lejeune
{"title":"口服 JAK3/TEC 家族激酶抑制剂 Ritlecitinib 治疗脱发症的综合安全性分析（来自 ALLEGRO 临床试验项目）。","authors":"Brett King, Jennifer Soung, Christos Tziotzios, Lidia Rudnicka, Pascal Joly, Melinda Gooderham, Rodney Sinclair, Natasha A. Mesinkovska, Carle Paul, Yankun Gong, Susan D. Anway, Helen Tran, Robert Wolk, Samuel H. Zwillich, Alexandre Lejeune","doi":"10.1007/s40257-024-00846-3","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).</p><h3>Objective</h3><p>The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.</p><h3>Methods</h3><p>Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.</p><h3>Results</h3><p>In the placebo-controlled cohort (<i>n</i> = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (<i>n</i> = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.</p><h3>Conclusions</h3><p>Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).</p><h3>Trial Registries</h3><p>ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"299 - 314"},"PeriodicalIF":8.6000,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867086/pdf/","citationCount":"0","resultStr":"{\"title\":\"Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program\",\"authors\":\"Brett King, Jennifer Soung, Christos Tziotzios, Lidia Rudnicka, Pascal Joly, Melinda Gooderham, Rodney Sinclair, Natasha A. Mesinkovska, Carle Paul, Yankun Gong, Susan D. Anway, Helen Tran, Robert Wolk, Samuel H. Zwillich, Alexandre Lejeune\",\"doi\":\"10.1007/s40257-024-00846-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).</p><h3>Objective</h3><p>The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.</p><h3>Methods</h3><p>Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.</p><h3>Results</h3><p>In the placebo-controlled cohort (<i>n</i> = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (<i>n</i> = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.</p><h3>Conclusions</h3><p>Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).</p><h3>Trial Registries</h3><p>ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).</p></div>\",\"PeriodicalId\":7706,\"journal\":{\"name\":\"American Journal of Clinical Dermatology\",\"volume\":\"25 2\",\"pages\":\"299 - 314\"},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-01-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867086/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Clinical Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s40257-024-00846-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Clinical Dermatology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40257-024-00846-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program
Background
The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).
Objective
The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.
Methods
Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.
Results
In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.
Conclusions
Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).
Trial Registries
ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).
期刊介绍：
The American Journal of Clinical Dermatology is dedicated to evidence-based therapy and effective patient management in dermatology. It publishes critical review articles and clinically focused original research covering comprehensive aspects of dermatological conditions. The journal enhances visibility and educational value through features like Key Points summaries, plain language summaries, and various digital elements, ensuring accessibility and depth for a diverse readership.
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