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While the reported safety data has remained scarce, especially for the controversial use of interferon. Identification of risk factors and comparative safety of different therapies will be beneficial for physicians to make decisions on rational usage of immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A nationwide retrospective cohort study consecutively collected advanced melanoma patients treated by anti\u2010PD\u20101 based therapies between July 1, 2018 and June 30, 2023. Univariate and multivariable logistic regression analysis was performed to identify the association between the potential risk factors and the occurrence of immune\u2010related adverse events (irAEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 508 advanced melanoma patients receiving PD\u20101 monotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009181), PD\u20101\u2009+\u2009tyrosine kinase inhibitors (TKI,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009131), PD\u20101\u2009+\u2009anti\u2010vascular endothelial growth factor (anti\u2010VEGF,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200956), PD\u20101\u2009+\u2009interferon Alfa\u20101b (IFN\u2010\u03b11b,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200999) and PD\u20101\u2009+\u2009IFN\u2010\u03b11b\u2009+\u2009TKI (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200941) were included. There was no significant difference in irAEs across subtypes of melanoma. While for patients with autoimmune disease of psoriasis and lichen planus, recurrence was observed after immunotherapy. Baseline renal or hepatic dysfunction and prior TKI therapy were risk factors for grade 3\u20135 irAEs. Multivariate logistic regression model found that compared with PD\u20101 monotherapy therapy, PD\u20101 based combination therapies had greater toxicity but were tolerated, except PD\u20101\u2009+\u2009IFN\u2010\u03b11b\u2009+\u2009TKI group. Notably, the triple therapy was associated with the highest risk of grade 3\u20135 irAEs (OR, 3.1; 95% CI: 1.2\u20138.1;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019), which led to a high rate of hospitalization and permanent treatment discontinuation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggested that PD\u20101\u2009+\u2009TKI, PD\u20101\u2009+\u2009anti\u2010VEGF, PD\u20101\u2009+\u2009IFN\u2010\u03b11b combination therapies have some adverse events but are generally tolerated sufficiently for continuation of treatment. While the triple therapy PD\u20101\u2009+\u2009IFN\u2010\u03b11b\u2009+\u2009TKI is not recommended because the benefits do not outweigh the risks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71694","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:45:17Z","timestamp":1776221117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Risk Factors and Comparative Safety of Anti\n                    <scp>\u2010PD<\/scp>\n                    \u20101 Combination Therapies in Advanced Melanoma: A Nationwide Real\u2010World Cohort Study From China"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1741-7980","authenticated-orcid":false,"given":"Yuan","family":"Qiao","sequence":"first","affiliation":[{"name":"School of Pharmacy Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"Department of Clinical Pharmacy Yan'an 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