{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:16:48Z","timestamp":1790252208639,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15- 2016-00048 \u2013 STAY ALIVE and GINOP-2.3.4-15-2020-00010"],"award-info":[{"award-number":["GINOP-2.3.2-15- 2016-00048 \u2013 STAY ALIVE and GINOP-2.3.4-15-2020-00010"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20\/50\/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.<\/jats:p>","DOI":"10.3390\/ijms23031246","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:32:52Z","timestamp":1642969972000},"page":"1246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5878-5232","authenticated-orcid":false,"given":"Lilla","family":"T\u00f3th","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rk F.","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Centre for Translational Medicine, Semmelweis University, H-1085 Budapest, Hungary"},{"name":"Heim P\u00e1l National Pediatric Institute, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Centre for Translational Medicine, Department of Medicine, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-4764","authenticated-orcid":false,"given":"Alan","family":"Abada","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Department of Anaesthesiology and Intensive Therapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fruzsina","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Somogy County Kaposi M\u00f3r Teaching Hospital, H-7400 Kaposv\u00e1r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Hegyi","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Centre for Translational Medicine, Semmelweis University, H-1085 Budapest, Hungary"},{"name":"Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, H-1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Farkas","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Institute of Bioanalysis, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Department of Internal Medicine and Oncology, Semmelweis University, H-1027 Budapest, Hungary"},{"name":"Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary"},{"name":"Heart and Vascular Centre, Semmelweis University, H-1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Research Centre and Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/annrheumdis-2015-207524","article-title":"Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force","volume":"75","author":"Smolen","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1136\/annrheumdis-2020-217344","article-title":"EULAR definition of difficult-to-treat rheumatoid arthritis","volume":"80","author":"Nagy","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41584-020-00541-7","article-title":"Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis","volume":"17","author":"Buch","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nrd.2017.201","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"16","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.semarthrit.2020.10.008","article-title":"The Jak\/STAT pathway: A focus on pain in rheumatoid arthritis","volume":"51","author":"Simon","year":"2021","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/acr.24596","article-title":"2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Care Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/acr.22783","article-title":"2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Arthritis Care Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/art.37816","article-title":"Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve-month data from a twenty-four-month phase III randomized radiographic study","volume":"65","author":"Tanaka","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1056\/NEJMoa1109071","article-title":"Tofacitinib or adalimumab versus placebo in rheumatoid arthritis","volume":"367","author":"Fleischmann","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.7326\/0003-4819-159-4-201308200-00006","article-title":"Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: A randomized trial","volume":"159","author":"Kremer","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0140-6736(12)61424-X","article-title":"Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: A randomised phase 3 trial","volume":"381","author":"Burmester","year":"2013","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa1109071","article-title":"Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis","volume":"367","author":"Fleischmann","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0140-6736(17)31618-5","article-title":"Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): A phase 3b\/4, double-blind, head-to-head, randomised controlled trial","volume":"390","author":"Fleischmann","year":"2017","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/art.33383","article-title":"Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs","volume":"64","author":"Fleischmann","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154","DOI":"10.5606\/ArchRheumatol.2018.6366","article-title":"Tofacitinib Versus Non-Tumor Necrosis Factor Biologics for Patients With Active Rheumatoid Arthritis","volume":"33","author":"Nakamura","year":"2018","journal-title":"Arch. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1136\/annrheumdis-2014-206028","article-title":"The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis","volume":"74","author":"Boyle","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1002\/art.24567","article-title":"The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo","volume":"60","author":"Kremer","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/art.33419","article-title":"A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone","volume":"64","author":"Kremer","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/acr.20494","article-title":"Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate","volume":"63","author":"Tanaka","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3109\/14397595.2014.995875","article-title":"Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: A 12-week, randomized, phase 2 study","volume":"25","author":"Tanaka","year":"2015","journal-title":"Mod. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1056\/NEJMoa1507247","article-title":"Baricitinib in Patients with Refractory Rheumatoid Arthritis","volume":"374","author":"Genovese","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/annrheumdis-2015-eular.6539","article-title":"Baricitinib, an oral janus kinase (jak)1\/jak2 inhibitor, in patients with active rheumatoid arthritis (RA) and an inadequate response to cDMARD therapy: Results of the phase 3 Ra-build study","volume":"74","author":"Dougados","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","first-page":"732","article-title":"Baricitinib in patients with rheumatoid arthritis with inadequate response to methotrexate: Results from a phase 3 study","volume":"38","author":"Li","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1136\/annrheumdis-2014-206478","article-title":"Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate","volume":"74","author":"Keystone","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3899\/jrheum.150613","article-title":"Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study","volume":"43","author":"Tanaka","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_30","first-page":"2172","article-title":"A randomized dose-ranging, placebo-controlled study of INCB028050, a selective JAK1 and JAK2 inhibitor in subjects with active rheumatoid arthritis","volume":"62","author":"Greenwald","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1016\/S0140-6736(19)30419-2","article-title":"Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): A randomised, placebo-controlled, double-blind phase 3 study","volume":"393","author":"Smolen","year":"2019","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1002\/art.41032","article-title":"Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial","volume":"71","author":"Fleischmann","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/S0140-6736(18)31115-2","article-title":"Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"391","author":"Burmester","year":"2018","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1002\/art.39808","article-title":"Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate","volume":"68","author":"Genovese","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1002\/art.39801","article-title":"A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy","volume":"68","author":"Kremer","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/S0140-6736(18)31116-4","article-title":"Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): A double-blind, randomised controlled phase 3 trial","volume":"391","author":"Genovese","year":"2018","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1056\/NEJMoa2008250","article-title":"Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis","volume":"383","author":"Enejosa","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1093\/rheumatology\/keaa084","article-title":"Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): A placebo-controlled phase IIb\/III study","volume":"59","author":"Kameda","year":"2020","journal-title":"Rheumatology"},{"key":"ref_39","first-page":"849","article-title":"Efficacy and safety of filgotinib for patients with rheumatoid arthritis with inadequate response to methotrexate: FINCH1 primary outcome results","volume":"71","author":"Combe","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1001\/jama.2019.9055","article-title":"Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial","volume":"322","author":"Genovese","year":"2019","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1136\/annrheumdis-2016-210105","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: Results from a randomised, dose-finding study (DARWIN 2)","volume":"76","author":"Kavanaugh","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1136\/annrheumdis-2016-210104","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: Results from a randomised, dose-finding study (DARWIN 1)","volume":"76","author":"Westhovens","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/art.40054","article-title":"Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease-Modifying Antirheumatic Drugs in the Treatment of Moderate-to-Severe Rheumatoid Arthritis","volume":"69","author":"Genovese","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/art.39955","article-title":"Peficitinib, a JAK Inhibitor, in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate","volume":"69","author":"Kivitz","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1136\/annrheumdis-2019-215164","article-title":"Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan","volume":"78","author":"Takeuchi","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1136\/annrheumdis-2019-215163","article-title":"Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: A randomised, double-blind, placebo-controlled phase III trial (RAJ3)","volume":"78","author":"Tanaka","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/art.39473","article-title":"VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis","volume":"68","author":"Genovese","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1136\/annrheumdis-2015-208901","article-title":"Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: Clinical and MRI findings","volume":"75","author":"Genovese","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/art.38949","article-title":"A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with active rheumatoid arthritis","volume":"67","author":"Fleischmann","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1002\/art.41316","article-title":"Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3\/TEC Inhibitor, in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate","volume":"72","author":"Robinson","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1136\/annrheumdis-2015-208267","article-title":"Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: Results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques","volume":"75","author":"Conaghan","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/art.41384","article-title":"Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderately-to-Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Multicenter, Multi-Country, Randomized, Double-Blind, Active Comparator\u2013Controlled Trial","volume":"72","author":"Takeuchi","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_53","first-page":"1606","article-title":"Efficacy and safety of filgotinib for patients with rheumatoid arthritis na\u00efve to methotrexate therapy: FINCH3 primary outcome results","volume":"71","author":"Westhovens","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1056\/NEJMoa1310476","article-title":"Tofacitinib versus methotrexate in rheumatoid arthritis","volume":"370","author":"Lee","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/art.39953","article-title":"Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment","volume":"69","author":"Fleischmann","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1136\/annrheumdis-2015-208279","article-title":"Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: A 12-week, randomised, double-blind, placebo-controlled phase IIb study","volume":"75","author":"Takeuchi","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","first-page":"976","article-title":"Comparison of efficacy of tofacitinib vs. etanercept treatment in rheumatoid arthtritis patients with high activity disease by ultrasound evaluation with power doppler (1 year treatment period)","volume":"77","author":"Menshikova","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1002\/art.40186","article-title":"Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK-1 Inhibitor, After Short-Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials","volume":"69","author":"Vanhoutte","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_59","first-page":"S765","article-title":"A randomized, dose-ranging, placebo-controlled, 84-day study of INCB039110, a selective janus kinase-1 inhibitor, in patients with active rheumatoid arthritis","volume":"65","author":"Luchi","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/annrheumdis-2016-210094","article-title":"Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study","volume":"76","author":"Dougados","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","first-page":"i44","article-title":"24-Week results of a blinded phase IIB dose-ranging study of baricitinib, an oral JAK1\/JAK2 inhibitor, in combination with traditional dmards in patients with rheumatoid arthritis","volume":"52","author":"Taylor","year":"2013","journal-title":"Rheumatology"},{"key":"ref_62","first-page":"S214","article-title":"12-and 24-week patient-reported outcomes from a phase 2B dose-ranging study of baricitinib, an oral janus kinase 1\/janus kinase 2 inhibitor, in combination with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis","volume":"64","author":"Smolen","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_63","first-page":"969","article-title":"Efficacy and safety of baricitinib in MTX-IR patients with rheumatoid arthritis: 52 week results from a phase 3 study (RA-balance)","volume":"77","author":"Li","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1136\/annrheumdis-2016-209821","article-title":"Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON)","volume":"76","author":"Smolen","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1136\/annrheumdis-2017-211259","article-title":"Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: Secondary analyses from the RA-BEAM study","volume":"76","author":"Keystone","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13075-017-1410-1","article-title":"Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment","volume":"19","author":"Schiff","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1136\/annrheumdis-2016-eular.1248","article-title":"Patient-reported outcomes from a phase 3 study of baricitinib in patients with early rheumatoid arthritis who had received limited or no treatment with disease-modifying anti-rheumatic drugs","volume":"75","author":"Schiff","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e000410","DOI":"10.1136\/rmdopen-2016-000410","article-title":"Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis","volume":"3","author":"Emery","year":"2017","journal-title":"RMD Open"},{"key":"ref_69","first-page":"S1004","article-title":"Effects of VX-509, an investigational oral selective janus kinase 3 (JAK3) inhibitor, on patient-reported outcomes in a phase 2A study of patients with active rheumatoid arthritis","volume":"65","author":"Strand","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_70","first-page":"3320","article-title":"A phase 2B, 12-week study of VX-509, an oral selective janus kinase 3 inhibitor, in combination with background methotrexate in rheumatoid arthritis","volume":"65","author":"Genovese","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_71","first-page":"S1234","article-title":"A phase 2b, randomized, double-blind, parallel-group, placebo-controlled, dose-finding, multi-center study to evaluate the safety and efficacy of asp015k in moderate to severe rheumatoid arthritis subjects not on concomitant methotrexate","volume":"66","author":"Genovese","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_72","first-page":"S421","article-title":"A phase 2b, randomized, double-blind, parallel-group, placebo-controlled, dose-finding, multi-center study to evaluate the safety and efficacy of ASP015K in moderate to severe rheumatoid arthritis subjects who have had an inadequate response to methotrexate","volume":"66","author":"Kivitz","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/ard.2009.108159","article-title":"Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: Results from a randomised, double-blind, placebo-controlled trial","volume":"69","author":"Coombs","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_74","first-page":"848","article-title":"Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: Patient-reported outcomes from the 24-month Phase 3 ORAL Scan study","volume":"38","author":"Strand","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s13075-015-0825-9","article-title":"Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs","volume":"17","author":"Strand","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1093\/rheumatology\/kev442","article-title":"Tofacitinib or adalimumab versus placebo: Patient-reported outcomes from a phase 3 study of active rheumatoid arthritis","volume":"55","author":"Strand","year":"2016","journal-title":"Rheumatology (Oxford)"},{"key":"ref_77","first-page":"1042","article-title":"Efficacy of adalimumab and tofacitinib in rheumatoid arthritis: Post-HOC analyses from a phase 3 study","volume":"75","author":"Cohen","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e000308","DOI":"10.1136\/rmdopen-2016-000308","article-title":"Tofacitinib versus methotrexate in rheumatoid arthritis: Patient-reported outcomes from the randomised phase III ORAL Start trial","volume":"2","author":"Strand","year":"2016","journal-title":"RMD Open"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e000232","DOI":"10.1136\/rmdopen-2015-000232","article-title":"Relationship between clinical and patient-reported outcomes in a phase 3 trial of tofacitinib or MTX in MTX-na\u00efve patients with rheumatoid arthritis","volume":"2","author":"Fleischmann","year":"2016","journal-title":"RMD Open"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/acr.22453","article-title":"Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: Patient-reported outcomes from a phase III trial","volume":"67","author":"Strand","year":"2015","journal-title":"Arthritis Care Res."},{"key":"ref_81","first-page":"2716","article-title":"Tofacitinib with and without methotrexate versus adalimumab with methotrexate for the treatment of rheumatoid arthritis: Patient-reported outcomes from a phase 3b\/4 randomized trial","volume":"69","author":"Strand","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e001040","DOI":"10.1136\/rmdopen-2019-001040","article-title":"Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: A phase IIIB\/IV trial","volume":"5","author":"Strand","year":"2019","journal-title":"RMD Open"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/acr.23004","article-title":"Tofacitinib in Combination with Conventional Disease-Modifying Antirheumatic Drugs in Patients with Active Rheumatoid Arthritis: Patient-Reported Outcomes from a Phase III Randomized Controlled Trial","volume":"69","author":"Strand","year":"2017","journal-title":"Arthritis Care Res."},{"key":"ref_84","first-page":"970","article-title":"Upadacitinib in patients with active rheumatoid arthritis and inadequate response or intolerance to biological dMARDS: A phase 3 randomized, placebocontrolled, double-blind study of a selective JAK1 inhibitor","volume":"77","author":"Genovese","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13075-019-2059-8","article-title":"Effects of upadacitinib on patient-reported outcomes: Results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs","volume":"21","author":"Strand","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_86","first-page":"738","article-title":"Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to methotrexate: Results from select-compare","volume":"78","author":"Strand","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_87","first-page":"372","article-title":"Upadacitinib monotherapy improves patientreported outcomes in methotrexate-na\u00efve patients with moderately to severely active rheumatoid arthritis: Results from selectearly","volume":"78","author":"Strand","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_88","first-page":"173","article-title":"A phase 3, randomized controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-na\u00efve patients with active rheumatoid arthritis","volume":"22","author":"Takeuchi","year":"2019","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_89","first-page":"2833","article-title":"Upadacitinib monotherapy improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to methotrexate","volume":"70","author":"Strand","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13075-019-2037-1","article-title":"Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: Results from SELECT-NEXT","volume":"21","author":"Strand","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/art.10515","article-title":"Preferences for improved health examined in 1024 patients with rheumatoid arthritis: Pain has highest priority","volume":"47","author":"Heiberg","year":"2002","journal-title":"Arthritis Care Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nrrheum.2014.64","article-title":"Mechanisms, impact and management of pain in rheumatoid arthritis","volume":"10","author":"Walsh","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.3389\/fimmu.2019.03061","article-title":"Neuraxial Cytokines in Pain States","volume":"10","author":"Delay","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1186\/s13075-014-0470-8","article-title":"Nociceptive neurons detect cytokines in arthritis","volume":"16","author":"Schaible","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1523\/JNEUROSCI.3338-07.2008","article-title":"Cytokine Mechanisms of Central Sensitization: Distinct and Overlapping Role of Interleukin-1\u03b2, Interleukin-6, and Tumor Necrosis Factor-\u03b1 in Regulating Synaptic and Neuronal Activity in the Superficial Spinal Cord","volume":"28","author":"Kawasaki","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.2174\/0929867323666160607120124","article-title":"Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain","volume":"23","author":"Mika","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/nm.2234","article-title":"Interactions between the immune and nervous systems in pain","volume":"16","author":"Ren","year":"2010","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/npp.2011.205","article-title":"Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior","volume":"37","author":"Haroon","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"668","DOI":"10.55563\/clinexprheumatol\/e7ayu8","article-title":"JAK\/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis","volume":"39","author":"Crispino","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759720X21999564","article-title":"Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: A systematic review and network meta-analysis","volume":"13","author":"Weng","year":"2021","journal-title":"Ther. Adv. Musculoskelet Dis."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Shamail, G.M.H., Haridoss, M., Natarajan, M., Joshua, V., and Bagepally, B.S. (2021). Association Between Janus Kinase Inhibitors Therapy and Mental Health Outcome in Rheumatoid Arthritis: A Systematic Review and Meta-analysis. Rheumatol. Ther.","DOI":"10.1007\/s40744-021-00409-6"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/art.40565","article-title":"The Impact of Targeted Rheumatoid Arthritis Pharmacologic Treatment on Mental Health: A Systematic Review and Network Meta-Analysis","volume":"70","author":"Matcham","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e000382","DOI":"10.1136\/rmdopen-2016-000382","article-title":"DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable","volume":"3","author":"Fleischmann","year":"2017","journal-title":"RMD Open"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00393-018-0531-5","article-title":"Comparison of the efficacy and safety of tofacitinib and baricitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials","volume":"78","author":"Bae","year":"2019","journal-title":"Z. Rheumatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00296-015-3291-4","article-title":"Comparative efficacy and safety of tofacitinib, with or without methotrexate, in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials","volume":"35","author":"Lee","year":"2015","journal-title":"Rheumatol. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s10067-013-2329-9","article-title":"The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: A systematic review and meta-analysis","volume":"32","author":"Kawalec","year":"2013","journal-title":"Clin. Rheumatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s10067-019-04684-1","article-title":"Defining response to TNF-inhibitors in rheumatoid arthritis: The negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders","volume":"38","author":"Johnson","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e000993","DOI":"10.1136\/rmdopen-2019-000993","article-title":"Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: Review of randomised controlled trials could point towards a paradigm shift","volume":"5","author":"Chatzidionysiou","year":"2019","journal-title":"RMD Open"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s00393-020-00889-x","article-title":"Comparative study of the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib versus methotrexate for disease-modifying antirheumatic drug-na\u00efve patients with rheumatoid arthritis","volume":"80","author":"Sung","year":"2021","journal-title":"Z. Rheumatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1177\/1759720X16665330","article-title":"Combination therapy with biologic agents in rheumatic diseases: Current and future prospects","volume":"8","author":"Inui","year":"2016","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_111","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2021). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (Updated February 2021), Wiley. Available online: www.training.cochrane.org\/handbook."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Claire, R., Gluud, C., Berlin, I., Coleman, T., and Leonardi-Bee, J. (2020). Using Trial Sequential Analysis for estimating the sample sizes of further trials: Example using smoking cessation intervention. BMC Med. Res. Methodol., 20.","DOI":"10.1186\/s12874-020-01169-7"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1001\/jama.2014.5559","article-title":"How to read a systematic review and meta-analysis and apply the results to patient care: Users\u2019 guides to the medical literature","volume":"312","author":"Murad","year":"2014","journal-title":"JAMA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:06:12Z","timestamp":1760133972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,23]]},"references-count":115,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031246"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031246","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,23]]}}}