George A Karpouzas, Zoltán Szekanecz, Eva Baecklund, Ted R Mikuls, Deepak L Bhatt, Cunshan Wang, Gosford A Sawyerr, Yan Chen, Sujatha Menon, Carol A Connell, Steven R Ytterberg, Mahta Mortezavi
{"title":"接受托法替尼或肿瘤坏死因子抑制剂治疗的患者的类风湿性关节炎疾病活动和不良事件：口服补液盐监测的事后分析。","authors":"George A Karpouzas, Zoltán Szekanecz, Eva Baecklund, Ted R Mikuls, Deepak L Bhatt, Cunshan Wang, Gosford A Sawyerr, Yan Chen, Sujatha Menon, Carol A Connell, Steven R Ytterberg, Mahta Mortezavi","doi":"10.1177/1759720X231201047","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs).</p><p><strong>Objectives: </strong>To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi).</p><p><strong>Design: </strong>This was a <i>post hoc</i> analysis of a long-term, postauthorization safety endpoint trial of tofacitinib <i>versus</i> TNFi.</p><p><strong>Methods: </strong>In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. <i>Post hoc</i> time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death.</p><p><strong>Results: </strong>Across treatments, risk for NSI was higher when patients had CDAI-defined active disease <i>versus</i> remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all <i>p</i> > 0.05.</p><p><strong>Conclusion: </strong>In ORAL Surveillance, higher NSI risk was observed in the presence of active RA <i>versus</i> remission. The risk of MACE and VTE directionally increased in active disease <i>versus</i> remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib <i>versus</i> TNFi.</p><p><strong>Registration: </strong>NCT02092467.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629315/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a <i>post hoc</i> analysis of ORAL Surveillance.\",\"authors\":\"George A Karpouzas, Zoltán Szekanecz, Eva Baecklund, Ted R Mikuls, Deepak L Bhatt, Cunshan Wang, Gosford A Sawyerr, Yan Chen, Sujatha Menon, Carol A Connell, Steven R Ytterberg, Mahta Mortezavi\",\"doi\":\"10.1177/1759720X231201047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs).</p><p><strong>Objectives: </strong>To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi).</p><p><strong>Design: </strong>This was a <i>post hoc</i> analysis of a long-term, postauthorization safety endpoint trial of tofacitinib <i>versus</i> TNFi.</p><p><strong>Methods: </strong>In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. <i>Post hoc</i> time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death.</p><p><strong>Results: </strong>Across treatments, risk for NSI was higher when patients had CDAI-defined active disease <i>versus</i> remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all <i>p</i> > 0.05.</p><p><strong>Conclusion: </strong>In ORAL Surveillance, higher NSI risk was observed in the presence of active RA <i>versus</i> remission. The risk of MACE and VTE directionally increased in active disease <i>versus</i> remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib <i>versus</i> TNFi.</p><p><strong>Registration: </strong>NCT02092467.</p>\",\"PeriodicalId\":23056,\"journal\":{\"name\":\"Therapeutic Advances in Musculoskeletal Disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-11-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629315/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Musculoskeletal Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/1759720X231201047\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Musculoskeletal Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/1759720X231201047","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance.
Background: In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs).
Objectives: To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi).
Design: This was a post hoc analysis of a long-term, postauthorization safety endpoint trial of tofacitinib versus TNFi.
Methods: In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. Post hoc time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death.
Results: Across treatments, risk for NSI was higher when patients had CDAI-defined active disease versus remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all p > 0.05.
Conclusion: In ORAL Surveillance, higher NSI risk was observed in the presence of active RA versus remission. The risk of MACE and VTE directionally increased in active disease versus remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib versus TNFi.
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