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Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy
Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical...
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Published in: | BMC rheumatology 2022-11, Vol.6 (1), p.64-64, Article 64 |
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description | Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.
We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.
We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).
The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes. |
doi_str_mv | 10.1186/s41927-022-00297-5 |
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We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.
We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).
The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.</description><identifier>ISSN: 2520-1026</identifier><identifier>EISSN: 2520-1026</identifier><identifier>DOI: 10.1186/s41927-022-00297-5</identifier><identifier>PMID: 36345032</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Anti-rheumatic therapy ; Autoimmune diseases ; Cancer ; Cytotoxicity ; Disease control ; Disease flare ; Electronic health records ; Immune checkpoint inhibitor ; Immune-related adverse event ; Lupus ; Medical records ; Oncology ; Patients ; Proteins ; Psoriatic arthritis ; Remission (Medicine) ; Rheumatoid arthritis ; Rheumatologic disease ; Steroids</subject><ispartof>BMC rheumatology, 2022-11, Vol.6 (1), p.64-64, Article 64</ispartof><rights>2022. The Author(s).</rights><rights>2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>The Author(s) 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-1650b436395788d6623cd1ebc3d393b33248388bde48f14edb60ed5d76bfd32d3</citedby><cites>FETCH-LOGICAL-c563t-1650b436395788d6623cd1ebc3d393b33248388bde48f14edb60ed5d76bfd32d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2848864760/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2848864760?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36345032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lusa, Amanda</creatorcontrib><creatorcontrib>Alvarez, Carolina</creatorcontrib><creatorcontrib>Saxena Beem, Shruti</creatorcontrib><creatorcontrib>Schwartz, Todd A</creatorcontrib><creatorcontrib>Ishizawar, Rumey</creatorcontrib><title>Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy</title><title>BMC rheumatology</title><addtitle>BMC Rheumatol</addtitle><description>Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.
We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.
We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).
The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.</description><subject>Anti-rheumatic therapy</subject><subject>Autoimmune diseases</subject><subject>Cancer</subject><subject>Cytotoxicity</subject><subject>Disease control</subject><subject>Disease flare</subject><subject>Electronic health records</subject><subject>Immune checkpoint inhibitor</subject><subject>Immune-related adverse event</subject><subject>Lupus</subject><subject>Medical records</subject><subject>Oncology</subject><subject>Patients</subject><subject>Proteins</subject><subject>Psoriatic arthritis</subject><subject>Remission (Medicine)</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatologic disease</subject><subject>Steroids</subject><issn>2520-1026</issn><issn>2520-1026</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdUsuO1DAQjBCIXQ37AxyQJS5cAn7FcS5IaMVjpJW4wNnyozPxkMTBdgb2zI_jnRlWu5zc6q4udZWrql4S_JYQKd4lTjra1pjSGmPatXXzpLqkDcU1wVQ8fVBfVFcp7XFBEdZ1hD2vLphgvMGMXlZ_ttO0zlBHGHUGh7Q7QEyA4ABzTsjPaNHZH-tfPg9oiVDDb5-yn3dIrzn44z6KA6yTzmEMO2-R8wl0YQkzOs_tAPbHEvycC-fgjc8hojxA1Mvti-pZr8cEV-d3U33_9PHb9Zf65uvn7fWHm9o2guWaiAYbXk7vmlZKJwRl1hEwljnWMcMY5ZJJaRxw2RMOzggMrnGtML1j1LFNtT3xuqD3aol-0vFWBe3VsRHiTumYvR1B6V4bzYtLjHZcW2Ma40jfEWNKi7dN4Xp_4lpWM4GzxaGox0ekjyezH9QuHFQnyscVEZvqzZkghp8rpKwmnyyMo54hrEnRlvGimBNWoK__g-7DGudilaKSSyl4K3BB0RPKxpBShP7-GILVXWTUKTKqREYdI6PuZLx6KON-5V9A2F8W8r_N</recordid><startdate>20221108</startdate><enddate>20221108</enddate><creator>Lusa, Amanda</creator><creator>Alvarez, Carolina</creator><creator>Saxena Beem, Shruti</creator><creator>Schwartz, Todd A</creator><creator>Ishizawar, Rumey</creator><general>BioMed Central</general><general>BMC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20221108</creationdate><title>Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy</title><author>Lusa, Amanda ; Alvarez, Carolina ; Saxena Beem, Shruti ; Schwartz, Todd A ; Ishizawar, Rumey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-1650b436395788d6623cd1ebc3d393b33248388bde48f14edb60ed5d76bfd32d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anti-rheumatic therapy</topic><topic>Autoimmune diseases</topic><topic>Cancer</topic><topic>Cytotoxicity</topic><topic>Disease control</topic><topic>Disease flare</topic><topic>Electronic health records</topic><topic>Immune checkpoint inhibitor</topic><topic>Immune-related adverse event</topic><topic>Lupus</topic><topic>Medical records</topic><topic>Oncology</topic><topic>Patients</topic><topic>Proteins</topic><topic>Psoriatic arthritis</topic><topic>Remission (Medicine)</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatologic disease</topic><topic>Steroids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lusa, Amanda</creatorcontrib><creatorcontrib>Alvarez, Carolina</creatorcontrib><creatorcontrib>Saxena Beem, Shruti</creatorcontrib><creatorcontrib>Schwartz, Todd A</creatorcontrib><creatorcontrib>Ishizawar, Rumey</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>BMC rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lusa, Amanda</au><au>Alvarez, Carolina</au><au>Saxena Beem, Shruti</au><au>Schwartz, Todd A</au><au>Ishizawar, Rumey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy</atitle><jtitle>BMC rheumatology</jtitle><addtitle>BMC Rheumatol</addtitle><date>2022-11-08</date><risdate>2022</risdate><volume>6</volume><issue>1</issue><spage>64</spage><epage>64</epage><pages>64-64</pages><artnum>64</artnum><issn>2520-1026</issn><eissn>2520-1026</eissn><abstract>Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.
We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.
We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).
The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>36345032</pmid><doi>10.1186/s41927-022-00297-5</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anti-rheumatic therapy Autoimmune diseases Cancer Cytotoxicity Disease control Disease flare Electronic health records Immune checkpoint inhibitor Immune-related adverse event Lupus Medical records Oncology Patients Proteins Psoriatic arthritis Remission (Medicine) Rheumatoid arthritis Rheumatologic disease Steroids |
title | Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy |
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