Meggan Mackay, Catriona A Wagner, Ashley Pinckney, Jeffrey A Cohen, Zachary S Wallace, Arezou Khosroshahi, Jeffrey A Sparks, Sandra Lord, Amit Saxena, Roberto Caricchio, Alfred Hj Kim, Diane L Kamen, Fotios Koumpouras, Anca D Askanase, Kenneth Smith, Joel M Guthridge, Gabriel Pardo, Yang Mao-Draayer, Susan Macwana, Sean McCarthy, Matthew A Sherman, Sanaz Daneshfar Hamrah, Maria Veri, Sarah Walker, Kate York, Sara Tedeschi, Jennifer Wang, Gabrielle Dziubla, Mike Castro, Robin Carroll, Sandeep Narpala, Bob C Lin, Leonid Serebryannyy, Adrian McDermott, William T Barry, Ellen Goldmuntz, James McNamara, Aimee S Payne, Amit Bar-Or, Dinesh Khanna, Judith A James
{"title":"Prospective SARS-CoV-2 Booster Vaccination in Immunosuppressant-Treated Systemic Autoimmune Disease Patients in a Randomized Controlled Trial.","authors":"Meggan Mackay, Catriona A Wagner, Ashley Pinckney, Jeffrey A Cohen, Zachary S Wallace, Arezou Khosroshahi, Jeffrey A Sparks, Sandra Lord, Amit Saxena, Roberto Caricchio, Alfred Hj Kim, Diane L Kamen, Fotios Koumpouras, Anca D Askanase, Kenneth Smith, Joel M Guthridge, Gabriel Pardo, Yang Mao-Draayer, Susan Macwana, Sean McCarthy, Matthew A Sherman, Sanaz Daneshfar Hamrah, Maria Veri, Sarah Walker, Kate York, Sara Tedeschi, Jennifer Wang, Gabrielle Dziubla, Mike Castro, Robin Carroll, Sandeep Narpala, Bob C Lin, Leonid Serebryannyy, Adrian McDermott, William T Barry, Ellen Goldmuntz, James McNamara, Aimee S Payne, Amit Bar-Or, Dinesh Khanna, Judith A James","doi":"10.1101/2025.03.25.25324558","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Autoimmune disease patients on immunosuppressants exhibit reduced humoral responses to primary COVID-19 vaccination. Booster vaccine responses and the effects of holding immunosuppression around vaccination are less studied. We evaluated the efficacy and safety of additional vaccination in mycophenolate mofetil/mycophenolic acid (MMF/MPA)-, methotrexate (MTX)-, and B cell-depleting therapy (BCDT)-treated autoimmune disease patients, including the impact of withholding MMF/MPA and MTX.</p><p><strong>Methods: </strong>In this open-label, multicenter, randomized trial, 22 MMF/MPA-, 26 MTX-, and 93 BCDT-treated autoimmune disease patients with negative or suboptimal antibody responses to initial COVID-19 vaccines (BNT162b2, mRNA-1273, or AD26.COV2.S) received a homologous booster. MMF/MPA and MTX participants were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 infections, and autoimmune disease activity through 48 weeks.</p><p><strong>Results: </strong>Additional vaccination increased anti-RBD concentrations in MMF/MPA and MTX patients, irrespective of whether immunosuppression was continued or withheld. BCDT-treated patients also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 infections occurred in 30-46% of participants, were predominantly mild, and included only two non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events.</p><p><strong>Conclusion: </strong>Additional COVID-19 vaccination is effective and safe in immunosuppressant-treated autoimmune disease patients, regardless of whether MMF/MPA or MTX is withheld. <b>Trial Registration.</b> ClinicalTrials.gov (NCT#05000216).</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974989/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv : the preprint server for health sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2025.03.25.25324558","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Autoimmune disease patients on immunosuppressants exhibit reduced humoral responses to primary COVID-19 vaccination. Booster vaccine responses and the effects of holding immunosuppression around vaccination are less studied. We evaluated the efficacy and safety of additional vaccination in mycophenolate mofetil/mycophenolic acid (MMF/MPA)-, methotrexate (MTX)-, and B cell-depleting therapy (BCDT)-treated autoimmune disease patients, including the impact of withholding MMF/MPA and MTX.
Methods: In this open-label, multicenter, randomized trial, 22 MMF/MPA-, 26 MTX-, and 93 BCDT-treated autoimmune disease patients with negative or suboptimal antibody responses to initial COVID-19 vaccines (BNT162b2, mRNA-1273, or AD26.COV2.S) received a homologous booster. MMF/MPA and MTX participants were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 infections, and autoimmune disease activity through 48 weeks.
Results: Additional vaccination increased anti-RBD concentrations in MMF/MPA and MTX patients, irrespective of whether immunosuppression was continued or withheld. BCDT-treated patients also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 infections occurred in 30-46% of participants, were predominantly mild, and included only two non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events.
Conclusion: Additional COVID-19 vaccination is effective and safe in immunosuppressant-treated autoimmune disease patients, regardless of whether MMF/MPA or MTX is withheld. Trial Registration. ClinicalTrials.gov (NCT#05000216).
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
