TNF-alpha Inhibitors in Organ Transplant Recipients: A Retrospective Cohort Study

TNF-alpha Inhibitors in Organ Transplant Recipients: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF correspondence TNF-alpha Inhibitors in Organ Transplant Recipients: A Retrospective Cohort Study Christopher Madden, Katherine G. Thompson, Isabelle T Smith, Jacqueline Ike, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4059750/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 May, 2024 Read the published version in Archives of Dermatological Research → Version 1 posted 7 You are reading this latest preprint version Abstract Tumor necrosis factor-alpha inhibitors (TNFi) can be an effective treatment for organ transplant recipients (OTR) with various diseases but can increase the risk of infection and drug interactions. 1 There is also a potential for acute graft rejection while on TNFi with an unclear causal relationship. Two patients experienced acute graft rejection out of sixteen in a retrospective study of kidney transplant patients on TNFi, but the rejections were deemed unlikely to be related to biologic use. 4 The purpose of this larger, multicenter study was to evaluate the safety of TNFi use in OTR by assessing rates of complications in patients treated with TNFi post-transplant. organ transplant epidemiology cohort study biologics infection drug safety Full Text Following IRB approval at Vanderbilt University Medical Center (VUMC) and Johns Hopkins Hospital (JHH), we queried both electronic health records and identified OTR who were prescribed a TNFi post-transplant. Chart review was conducted to retrieve patient demographics, transplant type, biologic type, baseline and follow-up labs, and complication history. The primary outcome was the occurrence of any infection, hospitalization for infection, sepsis, or rejection after starting a TNFi. R v4.0.2 was used for all analyses. We identified 223 OTR from VUMC prescribed a biologic after their transplant, 48 of whom started a TNFi. Of the 73 OTR from JHM on biologics, 39 patients were treated with a TNFi. The majority of patients were male with a mean age of 54±15 years. The types of organ transplants received by patients included: 50 kidney, 18 liver, 14 lung, 3 heart, and 2 pancreas (Table 1). Thirty-eight patients (44%) experienced at least one infectious complication post-transplant. Of the patients who developed an infection, twenty-two (25%) were hospitalized for infection and eight (9.2%) developed sepsis. Seventeen patients (20%) discontinued TNFi, and seven patients (8%) underwent modification of immunosuppressants secondary to TNFi use. Three patients (3.4%) experienced rejection while receiving TNFi. Mean leukocyte, hemoglobin, and platelet counts (Table 2) were not significantly changed from baseline when trended over the course of two years post-transplant. Adverse effects of TNFi have previously been described in post-marketing studies. TNFi have shown infection rates ranging from 35% to 52.7% in otherwise immunocompetent patients with most occurring within one year of initiation. 3 There are currently no reports in the literature to compare baseline rates of hospitalizations or sepsis in OTR specifically taking TNFi. Several limitations may impact our results. All included patients were treated at tertiary care academic centers with high-volume transplant centers, which may not be representative of the general population. Additionally, VUMC and JHM participate in an open healthcare system, and the charts reviewed might not have captured all of the potential complications. Lastly, we do not have evidence that any of the experienced complications were directly caused by TNFi, and we cannot predict if these complications would have occurred regardless of TNFi treatment. Findings from this retrospective cohort study have demonstrated results similar to previously described adverse effects in post-marketing studies for TNFi. These results add further evidence regarding the safety of TNFi in OTR. Abbreviations TNFi – TNF-alpha inhibitors OTR – organ transplant recipients VUMC – Vanderbilt University Medical Center JHM – Johns Hopkins Medicine Declarations Funding: Dr. Wheless is supported by a grant from the Skin Cancer Foundation, a Physician Scientist Career Development Award from the Dermatology Foundation and VA CSR&D grant CX-002452. The project described was supported by CTSA award No. UL1TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Dr. Bibee is supported by a Dermatologic Surgery Career Development Award from the Dermatology Foundation. Conflict of interest: The authors have no conflicts to declare Study approved as exempt non-human subjects research, VUMC IRB #200335, JHM IRB #IRB00398143) References Bryant PA, Baddley JW. Opportunistic Infections in Biological Therapy, Risk and Prevention. Rheum Dis Clin N Am. 2017;43(1):27-41. doi:10.1016/j.rdc.2016.09.005 Patel R, Paya CV. Infections in solid-organ transplant recipients. Clin Microbiol Rev. 1997;10(1):86-124. Khanna D, McMahon M, Furst DE. Safety of Tumour Necrosis Factor-α Antagonists. Drug Saf. 2004;27(5):307-324. doi:10.2165/00002018-200427050-00003 Garrouste C, Anglicheau D, Kamar N, et al. Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes. Medicine (Baltimore). 2016;95(41):e5108. doi:10.1097/MD.0000000000005108 Tables Table 1. Baseline characteristics and complication rates of transplant patients treated with TNF-alpha inhibitors Characteristic N = 87 1 Demographics Sex F 40 (46%) M 47 (54%) Race Black 10 (11%) Hispanic 1 (1.1%) Multiracial 1 (1.1%) Native Hawaiian or Other Pacific Islander 2 (2.3%) White 73 (84%) Ethnicity Hispanic/Latino 2 (2.3%) Not Hispanic/Latino 84 (97%) Unknown 1 (1.1%) Age 54 (15) Organ Heart 3 (3.4%) Kidney 50 (57%) Liver 18 (21%) Lung 14 (16%) Pancreas/GI 2 (2.3%) TNF Inhibitors Etanercept 19 (22%) Adalimumab 45 (52%) Infliximab 23 (26%) Indication for TNF Inhibitor Crohn's Disease 19 (22%) Hidradenitis Suppurativa 1 (1.1%) Psoriasis 16 (18%) Psoriatic Arthritis 7 (8.0%) Rheumatoid Arthritis 13 (15%) Ulcerative Colitis 16 (18%) Other 15 (17%) Complications Rejection while taking TNF Inhibitor 3 (3.4%) Immunosuppressive medications adjusted 7 (8.0%) TNF Inhibitor discontinued 17 (20%) Infection 38 (44%) Hospitalization 22 (25%) Sepsis 8 (9.2%) 1 n (%); Mean (SD) Table 2. Rates of complications in transplant patients treated with TNF-alpha inhibitors Laboratory Values Baseline (n=73) 1 Post-Transplant (n=73) 1 p-value 2 Hemoglobin (g/dL) 11.50 (2.26) 11.79 (1.89) 0.5 Platelets (103/mL) 193 (130) 189 (75) 0.6 Leukocyte count (103/mL) 3 6.7 (3.6) 7.3 (2.7) 0.058 1 Mean (SD) 2 Wilcoxon rank sum test 3 Baseline data available for 66 of 77 patients. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 May, 2024 Read the published version in Archives of Dermatological Research → Version 1 posted Editorial decision: Accepted 26 Apr, 2024 Reviews received at journal 22 Apr, 2024 Reviewers agreed at journal 13 Apr, 2024 Reviewers invited by journal 27 Mar, 2024 Editor assigned by journal 11 Mar, 2024 Submission checks completed at journal 11 Mar, 2024 First submitted to journal 09 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4059750","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"correspondence","associatedPublications":[],"authors":[{"id":291326053,"identity":"baa8feaf-bd80-4612-ba62-bcb3bd2ee267","order_by":0,"name":"Christopher Madden","email":"","orcid":"","institution":"Vanderbilt University Medical Center (VUMC)","correspondingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"","lastName":"Madden","suffix":""},{"id":291326054,"identity":"5f30eeaf-50d9-4d0c-b871-1dd8cd6f2361","order_by":1,"name":"Katherine G. Thompson","email":"","orcid":"","institution":"Johns Hopkins Department of Dermatology","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"G.","lastName":"Thompson","suffix":""},{"id":291326055,"identity":"c77191d7-504d-4cd4-9855-c80bc32b433b","order_by":2,"name":"Isabelle T Smith","email":"","orcid":"","institution":"Vanderbilt University Medical Center (VUMC)","correspondingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"T","lastName":"Smith","suffix":""},{"id":291326056,"identity":"34a2bd7b-2c27-43c4-95f1-77ee9bb8532f","order_by":3,"name":"Jacqueline Ike","email":"","orcid":"","institution":"Meharry Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jacqueline","middleName":"","lastName":"Ike","suffix":""},{"id":291326057,"identity":"68c5b0b8-d725-47c6-9abf-dbb67d5de275","order_by":4,"name":"Briana R Halle","email":"","orcid":"","institution":"Vanderbilt University Medical Center (VUMC)","correspondingAuthor":false,"prefix":"","firstName":"Briana","middleName":"R","lastName":"Halle","suffix":""},{"id":291326058,"identity":"69f985eb-b670-4b34-a7ba-9b2c35d52a3d","order_by":5,"name":"Carolyn Ahlers","email":"","orcid":"","institution":"Duke University","correspondingAuthor":false,"prefix":"","firstName":"Carolyn","middleName":"","lastName":"Ahlers","suffix":""},{"id":291326059,"identity":"71a07a47-0676-4c02-b24a-4bf32edb6f4b","order_by":6,"name":"Dominique Mosley","email":"","orcid":"","institution":"Vanderbilt University Medical Center (VUMC)","correspondingAuthor":false,"prefix":"","firstName":"Dominique","middleName":"","lastName":"Mosley","suffix":""},{"id":291326060,"identity":"23ecc85a-3b19-4196-b29d-9511fd17cb21","order_by":7,"name":"Sarah Grossarth","email":"","orcid":"","institution":"Quillen College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Grossarth","suffix":""},{"id":291326061,"identity":"f2ccebf8-a4f5-44cc-93cf-8516a4cd5871","order_by":8,"name":"Kristin Bibee","email":"","orcid":"","institution":"Johns Hopkins Department of Dermatology","correspondingAuthor":false,"prefix":"","firstName":"Kristin","middleName":"","lastName":"Bibee","suffix":""},{"id":291326062,"identity":"4a928cd9-a940-4cd0-93da-1145d0803fe4","order_by":9,"name":"Lee Wheless","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYBACPiidwMAOoiqI0MIG18IMos6QrIWxjRgt7M0HGD4wHM7jZ2Y+/PHnvMOJa9sPMD6u+IVHC8+xBMYZDIeLJZvZ0qR5tx1O3HYmgdnwbB8eLRI5Bsw8DLcTNxzmMWNm3JaWuO0GA5tkYw8eLfLvPzD/AWrZf5j/88efc4jRIsED8jjQFqBdErwNNhAtDT/w+SXN4GCPwf/EGYfZzKR5jtkYbzuT2GzY2IBbCz/74YcPflSkJfa3Nz/++KNGQnbb8cMHHzb8wa0FBA4wGKDwGRuIiyA0QMCWUTAKRsEoGFEAALYaUGtHmjVwAAAAAElFTkSuQmCC","orcid":"","institution":"Tennessee Valley VA Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Lee","middleName":"","lastName":"Wheless","suffix":""}],"badges":[],"createdAt":"2024-03-09 20:35:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4059750/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4059750/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00403-024-02944-y","type":"published","date":"2024-05-17T09:51:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":57685517,"identity":"e238497f-efa7-4df2-8808-7a7fcfb0ca77","added_by":"auto","created_at":"2024-06-04 09:51:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":286602,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4059750/v1/a30a527e-7853-49e2-a275-26b67922fee3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"TNF-alpha Inhibitors in Organ Transplant Recipients: A Retrospective Cohort Study","fulltext":[{"header":"Full Text","content":"\u003cp\u003eFollowing IRB approval at Vanderbilt University Medical Center (VUMC) and Johns Hopkins Hospital (JHH), we queried both electronic health records and identified OTR who were prescribed a TNFi post-transplant. Chart review was conducted to retrieve patient demographics, transplant type, biologic type, baseline and follow-up labs, and complication history. The primary outcome was the occurrence of any infection, hospitalization for infection, sepsis, or rejection after starting a TNFi. R v4.0.2 was used for all analyses.\u003c/p\u003e\n\u003cp\u003eWe identified 223 OTR from VUMC prescribed a biologic after their transplant, 48 of whom started a TNFi. Of the 73 OTR from JHM on biologics, 39 patients were treated with a TNFi. The majority of patients were male with a mean age of 54\u0026plusmn;15 years. The types of organ transplants received by patients included: 50 kidney, 18 liver, 14 lung, 3 heart, and 2 pancreas (Table 1). \u003c/p\u003e\n\u003cp\u003eThirty-eight patients (44%) experienced at least one infectious complication post-transplant. Of the patients who developed an infection, twenty-two (25%) were hospitalized for infection and eight (9.2%) developed sepsis. Seventeen patients (20%) discontinued TNFi, and seven patients (8%) underwent modification of immunosuppressants secondary to TNFi use. Three patients (3.4%) experienced rejection while receiving TNFi. Mean leukocyte, hemoglobin, and platelet counts (Table 2) were not significantly changed from baseline when trended over the course of two years post-transplant. \u003c/p\u003e\n\u003cp\u003eAdverse effects of TNFi have previously been described in post-marketing studies. TNFi have shown infection rates ranging from 35% to 52.7% in otherwise immunocompetent patients with most occurring within one year of initiation.\u003csup\u003e3\u003c/sup\u003e There are currently no reports in the literature to compare baseline rates of hospitalizations or sepsis in OTR specifically taking TNFi. \u003c/p\u003e\n\u003cp\u003eSeveral limitations may impact our results. All included patients were treated at tertiary care academic centers with high-volume transplant centers, which may not be representative of the general population. Additionally, VUMC and JHM participate in an open healthcare system, and the charts reviewed might not have captured all of the potential complications. Lastly, we do not have evidence that any of the experienced complications were directly caused by TNFi, and we cannot predict if these complications would have occurred regardless of TNFi treatment. \u003c/p\u003e\n\u003cp\u003eFindings from this retrospective cohort study have demonstrated results similar to previously described adverse effects in post-marketing studies for TNFi. These results add further evidence regarding the safety of TNFi in OTR. \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTNFi \u0026ndash; TNF-alpha inhibitors\u003c/p\u003e\n\u003cp\u003eOTR \u0026ndash; organ transplant recipients\u003c/p\u003e\n\u003cp\u003eVUMC \u0026ndash; Vanderbilt University Medical Center\u003c/p\u003e\n\u003cp\u003eJHM \u0026ndash; Johns Hopkins Medicine\u003c/p\u003e"},{"header":"Declarations ","content":"\u003cp\u003eFunding: \u003cem\u003eDr. Wheless is supported by a grant from the Skin Cancer Foundation, a Physician Scientist Career Development Award from the Dermatology Foundation and VA CSR\u0026amp;D grant CX-002452. \u0026nbsp;The project described was supported by CTSA award No. \u003cstrong\u003eUL1TR000445\u003c/strong\u003e from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.\u0026nbsp;Dr. Bibee is supported by a Dermatologic Surgery Career Development Award from the Dermatology Foundation.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eConflict of interest: The authors have no conflicts to declare\u003c/p\u003e\n\u003cp\u003eStudy approved as exempt non-human subjects research, VUMC IRB #200335, JHM IRB #IRB00398143)\u003c/p\u003e"},{"header":"References","content":"1.\tBryant PA, Baddley JW. Opportunistic Infections in Biological Therapy, Risk and Prevention. Rheum Dis Clin N Am. 2017;43(1):27-41. doi:10.1016/j.rdc.2016.09.005\n2.\tPatel R, Paya CV. Infections in solid-organ transplant recipients. Clin Microbiol Rev. 1997;10(1):86-124.\n3.\tKhanna D, McMahon M, Furst DE. Safety of Tumour Necrosis Factor-α Antagonists. Drug Saf. 2004;27(5):307-324. doi:10.2165/00002018-200427050-00003\n4.\tGarrouste C, Anglicheau D, Kamar N, et al. Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes. Medicine (Baltimore). 2016;95(41):e5108. doi:10.1097/MD.0000000000005108\n"},{"header":"Tables","content":"\u003cp\u003eTable 1. Baseline characteristics and complication rates of transplant patients treated with TNF-alpha inhibitors\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN = 87\u003c/strong\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e40 (46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e47 (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Black\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e10 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Multiracial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Native Hawaiian or Other Pacific Islander\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e73 (84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Hispanic/Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Not Hispanic/Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e84 (97%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e54 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrgan\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Heart\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Kidney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e50 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Liver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e18 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Lung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e14 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Pancreas/GI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTNF Inhibitors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Etanercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e19 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Adalimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e45 (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Infliximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e23 (26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication for TNF Inhibitor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Crohn\u0026apos;s Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e19 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Hidradenitis Suppurativa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Psoriasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e16 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Psoriatic Arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Rheumatoid Arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e13 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Ulcerative Colitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e16 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e15 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eComplications\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eRejection while taking TNF Inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eImmunosuppressive medications adjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eTNF Inhibitor discontinued\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e17 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e38 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eHospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e22 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"80.8080808080808%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e8 (9.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003en (%); Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Rates of complications in transplant patients treated with TNF-alpha inhibitors\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory Values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e (n=73)\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-Transplant\u003c/strong\u003e (n=73)\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.50 (2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.79 (1.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePlatelets (103/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e193 (130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e189 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeukocyte count (103/mL)\u003cem\u003e\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.7 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.3 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003eWilcoxon rank sum test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003eBaseline data available for 66 of 77 patients.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"organ transplant, epidemiology, cohort study, biologics, infection, drug safety","lastPublishedDoi":"10.21203/rs.3.rs-4059750/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4059750/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTumor necrosis factor-alpha inhibitors (TNFi) can be an effective treatment for organ transplant recipients (OTR) with various diseases but can increase the risk of infection and drug interactions.\u003csup\u003e1\u003c/sup\u003e There is also a potential for acute graft rejection while on TNFi with an unclear causal relationship. Two patients experienced acute graft rejection out of sixteen in a retrospective study of kidney transplant patients on TNFi, but the rejections were deemed unlikely to be related to biologic use.\u003csup\u003e4\u003c/sup\u003e\u0026nbsp; The purpose of this larger, multicenter study was to evaluate the safety of TNFi use in OTR by assessing rates of complications in patients treated with TNFi post-transplant.\u003c/p\u003e","manuscriptTitle":"TNF-alpha Inhibitors in Organ Transplant Recipients: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-16 05:37:30","doi":"10.21203/rs.3.rs-4059750/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2024-04-26T15:13:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-22T20:21:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"a14da14b-7bb4-454e-86a8-3614f0ff6c67","date":"2024-04-13T21:09:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-27T22:11:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-11T10:58:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-11T10:58:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2024-03-09T20:33:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"252a830d-8658-4b50-a04a-1d23dfa14336","owner":[],"postedDate":"April 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-04T09:51:12+00:00","versionOfRecord":{"articleIdentity":"rs-4059750","link":"https://doi.org/10.1007/s00403-024-02944-y","journal":{"identity":"archives-of-dermatological-research","isVorOnly":false,"title":"Archives of Dermatological Research"},"publishedOn":"2024-05-17 09:51:12","publishedOnDateReadable":"May 17th, 2024"},"versionCreatedAt":"2024-04-16 05:37:30","video":"","vorDoi":"10.1007/s00403-024-02944-y","vorDoiUrl":"https://doi.org/10.1007/s00403-024-02944-y","workflowStages":[]},"version":"v1","identity":"rs-4059750","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4059750","identity":"rs-4059750","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}