{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T19:39:36Z","timestamp":1774553976388,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate unacceptable pain [UP; visual analogue scale (VAS) &amp;gt;40\u2009mm] and uncontrolled inflammation [C-reactive protein (CRP) \u22651.0\u2009mg\/dL] in patients with active rheumatoid arthritis (RA) receiving sarilumab (SAR) as monotherapy or in combination with non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (SAR\u2009+\u2009csDMARDs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In the HARUKA Phase 3 study (NCT02373202), Japanese patients received either SAR monotherapy (n\u2009=\u200961) or SAR\u2009+\u2009csDMARDs (n\u2009=\u200930). In this post-hoc analysis, changes in the proportions of patients with\/without UP and controlled\/uncontrolled inflammation were assessed over 52\u2009weeks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At baseline, 80.3% (49\/61) of patients receiving SAR monotherapy had UP and this proportion decreased with treatment to 55.9% (33\/59) at Week 4 and 15.5% (9\/58) at Week 52. The SAR\u2009+\u2009csDMARDs group achieved a reduction in UP from 73.3% (22\/30) at baseline to 34.5% (10\/29) at Week 4 and 0% (0\/24) by Week 52. At baseline, 34.4% (21\/61) and 50% (15\/30) of patients had both UP and uncontrolled inflammation in the SAR monotherapy and SAR\u2009+\u2009csDMARDs groups; by Week 2, the proportions decreased to 6.6% (4\/61) and 3.3% (1\/30), respectively; and 0% in both groups by Week 52.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>UP and inflammation were reduced in patients with active RA in Japan in both SAR monotherapy and SAR\u2009+\u2009csDMARDs treatment groups.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mr\/roae055","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T07:49:14Z","timestamp":1722066554000},"page":"27-33","source":"Crossref","is-referenced-by-count":2,"title":["The effects of sarilumab as monotherapy and in combination with non-methotrexate disease-modifying anti-rheumatic drugs on unacceptable pain in patients with rheumatoid arthritis: A post-hoc analysis of the HARUKA phase 3 study"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"first","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Fukuoka,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Asahi Kasei Pharma Corporation , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"van Hoogstraten","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Sanofi US , Bridgewater, NJ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Kato","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Asahi Kasei Pharma Corporation , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4330-5782","authenticated-orcid":false,"given":"Hideto","family":"Kameda","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"2025020515445092200_R1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2019.102400","article-title":"The etiology of rheumatoid arthritis","volume":"110","author":"Scherer","year":"2020","journal-title":"J Autoimmun"},{"key":"2025020515445092200_R2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s11914-018-0473-5","article-title":"Mechanisms for joint pain in rheumatoid arthritis (ra): from cytokines to central sensitization","volume":"16","author":"Zhang","year":"2018","journal-title":"Curr Osteoporos Rep"},{"key":"2025020515445092200_R3","first-page":"286","article-title":"Extra-articular manifestations in rheumatoid arthritis","volume":"5","author":"Cojocaru","year":"2010","journal-title":"Maedica (Bucur)"},{"key":"2025020515445092200_R4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1080\/03009742.2020.1729404","article-title":"Unacceptable pain in the BARFOT inception cohort of patients with rheumatoid arthritis: a long-term study","volume":"49","author":"Svensson","year":"2020","journal-title":"Scand J Rheumatol"},{"key":"2025020515445092200_R5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.4081\/reumatismo.2014.760","article-title":"Pain in rheumatoid arthritis: a critical review","volume":"66","author":"Sarzi-Puttini","year":"2014","journal-title":"Reumatismo"},{"key":"2025020515445092200_R6","doi-asserted-by":"crossref","DOI":"10.1007\/s11926-016-0581-0","article-title":"Non-inflammatory causes of pain in patients with rheumatoid arthritis","volume":"18","author":"Boyden","year":"2016","journal-title":"Curr Rheumatol Rep"},{"key":"2025020515445092200_R7","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/rheumatology\/kex391","article-title":"Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis","volume":"57","author":"Choy","year":"2018","journal-title":"Rheumatology (Oxford)"},{"key":"2025020515445092200_R8","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1002\/art.22923","article-title":"Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers","volume":"56","author":"Young-Min","year":"2007","journal-title":"Arthritis Rheum"},{"key":"2025020515445092200_R9","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/acr.21723","article-title":"Predictors of change in bodily pain in early rheumatoid arthritis: an inception cohort study","volume":"64","author":"McWilliams","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2025020515445092200_R10","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1002\/art.39238","article-title":"Determining pathways to improvements in fatigue in rheumatoid arthritis: results from the British Society for Rheumatology biologics register for rheumatoid arthritis","volume":"67","author":"Druce","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2025020515445092200_R11","doi-asserted-by":"crossref","DOI":"10.1186\/ar3353","article-title":"Pain persists in DAS28 rheumatoid arthritis remission but not in ACR\/EULAR remission: a longitudinal observational study","volume":"13","author":"Lee","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"2025020515445092200_R12","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-019-2042-4","article-title":"Association between pain phenotype and disease activity in rheumatoid arthritis patients: a non-interventional, longitudinal cohort study","volume":"21","author":"Ten Klooster","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"2025020515445092200_R13","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2018-000887","article-title":"Long-term safety and efficacy of sarilumab plus methotrexate on disease activity, physical function and radiographic progression: 5 years of sarilumab plus methotrexate treatment","volume":"5","author":"Genovese","year":"2019","journal-title":"RMD Open"},{"key":"2025020515445092200_R14","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/2076328","article-title":"Pain mechanism in rheumatoid arthritis: from cytokines to central sensitization","volume":"2020","author":"Cao","year":"2020","journal-title":"Mediators Inflamm"},{"key":"2025020515445092200_R15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2147\/OARRR.S291388","article-title":"Pain: a review of interleukin-6 and its roles in the pain of rheumatoid arthritis","volume":"13","author":"Sebba","year":"2021","journal-title":"Open Access Rheumatol"},{"key":"2025020515445092200_R16","article-title":"Kevzara (sarilumab) prescribing information","author":"U.S. Food and drug administration"},{"key":"2025020515445092200_R17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s40265-018-0929-z","article-title":"Sarilumab: a review in moderate to severe rheumatoid arthritis","volume":"78","author":"Lamb","year":"2018","journal-title":"Drugs"},{"key":"2025020515445092200_R18","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/14397595.2019.1639939","article-title":"Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: a Japan phase 3 trial (HARUKA)","volume":"30","author":"Kameda","year":"2020","journal-title":"Mod Rheumatol"},{"key":"2025020515445092200_R19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/mr\/roac017","article-title":"Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication","volume":"33","author":"Kawahito","year":"2023","journal-title":"Mod Rheumatol"},{"key":"2025020515445092200_R20","volume-title":"Harrison\u2019s Principles of Internal Medicine","author":"Kasper","year":"2015","edition":"19th"},{"key":"2025020515445092200_R21","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1136\/annrheumdis-2016-210310","article-title":"Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial","volume":"76","author":"Burmester","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2025020515445092200_R22","article-title":"Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan","volume":"21","author":"Tanaka","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"2025020515445092200_R23","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/art.39944","article-title":"Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors","volume":"69","author":"Fleischmann","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2025020515445092200_R24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/mr\/road073","article-title":"Effect of sarilumab on unacceptable pain and inflammation control in Japanese patients with moderately-to-severely active rheumatoid arthritis: post hoc analysis of a phase III study (KAKEHASI)","volume":"34","author":"Tanaka","year":"2023","journal-title":"Mod Rheumatol"},{"key":"2025020515445092200_R25","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/jcpt.13122","article-title":"Polypharmacy in elderly patients in Japan: analysis of Japanese real-world databases","volume":"45","author":"Mabuchi","year":"2020","journal-title":"J Clin Pharm Ther"},{"key":"2025020515445092200_R26","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1093\/rheumatology\/keac659","article-title":"Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab","volume":"62","author":"Choy","year":"2022","journal-title":"Rheumatol"},{"key":"2025020515445092200_R27","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-016-0607-6","article-title":"Interleukin-6: an emerging regulator of pathological pain","volume":"13","author":"Zhou","year":"2016","journal-title":"J Neuroinflammation"}],"container-title":["Modern Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mr\/advance-article-pdf\/doi\/10.1093\/mr\/roae055\/58800403\/roae055.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/35\/1\/27\/58800403\/roae055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/35\/1\/27\/58800403\/roae055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T15:45:15Z","timestamp":1738770315000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mr\/article\/35\/1\/27\/7723261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,29]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,7,29]]},"published-print":{"date-parts":[[2024,12,25]]}},"URL":"https:\/\/doi.org\/10.1093\/mr\/roae055","relation":{},"ISSN":["1439-7595","1439-7609"],"issn-type":[{"value":"1439-7595","type":"print"},{"value":"1439-7609","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,7,29]]}}}