eb5b28de90dceedf41ed9ca57934c639 pmc_11050893.pdf 000145d55bbd8b496e0b2463bf2f9a8a49553636 pmc_11050893.pdf 905b08cc779978e66d38933044165fe65dc06f8ae583a428bb473b6505205f41 pmc_11050893.pdf Title: Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients? Subject: Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan–Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy. Keywords: rheumatoid arthritis; Janus kinase inhibitor; tofacitinib; baricitinib; upadacitinib; filgotinib; treat-to-target; treatment effectiveness; sex-related differences Author: Cristina Martinez-Molina, Anna Feliu, Hye S. Park, Ana Juanes, Cesar Diaz-Torne, Silvia Vidal and Hèctor Corominas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Apr 18 12:25:08 2024 CEST ModDate: Thu Apr 18 12:28:00 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 797961 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WYEKQU+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes yes 16 0 FLRGZB+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 SXCDLZ+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 WKMFNO+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 51 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 73 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 77 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 81 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 85 0 IKKWKP+CMSY10 Type 1 Builtin yes yes yes 96 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 104 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 120 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 124 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 128 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 132 0 TimesNewRomanPSMT TrueType WinAnsi no no no 139 0 ArialMT TrueType WinAnsi no no no 143 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-09 02:45:39 CEST RepresentationInformation: pmc_11050893.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-05-08 02:36:18 CEST Size: 797961 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 236 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Patient Population Destination: subsection.2.1 Item: Title: Assessments Destination: subsection.2.2 Item: Title: Statistical Analyses Destination: subsection.2.3 Item: Title: Ethics Approval and Consent to Participate Destination: subsection.2.4 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients? Author: Cristina Martinez-Molina, Anna Feliu, Hye S. Park, Ana Juanes, Cesar Diaz-Torne, Silvia Vidal and Hèctor Corominas Subject: Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy. 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