{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:24:23Z","timestamp":1792621463624,"version":"4.5.0"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"\n Importance<\/jats:title>\n Knee osteoarthritis (OA) is disabling, with few effective treatments. Anti-inflammatory treatments may be effective for patients with an inflammatory phenotype.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To evaluate the efficacy of the interleukin-1\u03b2 blocker diacerein, compared with placebo, on knee pain in people with knee OA who have substantial knee pain and inflammation (effusion-synovitis on magnetic resonance imaging).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 4 Australian centers. Participants with clinical knee OA, substantial knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from June 2019 to September 2022. Final follow-up occurred on February 6, 2023. Data analysis began on July 7, 2023.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized (1:1) to diacerein, 50 mg, once daily or identical placebo for the first 2 weeks, which increased to 50 mg, twice daily until 24 weeks if adverse effects were tolerable.<\/jats:p>\n <\/jats:sec>\n \n Main outcomes and Measures<\/jats:title>\n The primary outcome was change in knee pain as assessed by the visual analogue scale (range, 0-100 mm; minimal clinically important improvement, 15) over 24 weeks.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 262 participants randomized (mean [SD] age, 54.9 [6.1] years; 147 [56.1%] female and 115 [43.9%] male), 231 (88.2%) completed the trial. Compared with placebo, diacerein did not improve knee pain over 24 weeks (\u221219.9 mm [diacerein] vs \u221218.6 mm [placebo]; between-group mean difference, \u22121.3 mm; 95% CI, \u22129.8 to 7.3). The most common adverse events were gastrointestinal symptoms, which occurred in 55 participants (41.7%) in the diacerein group and 33 (25.4%) in the placebo group, most commonly diarrhea (51 [38.6%] in the diacerein group vs 29 [22.3%] in the placebo group). Change in urine color was observed among 13 participants (9.8%) who received diacerein.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This randomized clinical trial found that, in patients with symptomatic knee OA and effusion-synovitis, diacerein (50 mg, twice daily) over 24 weeks resulted in no greater improvement in knee pain compared with placebo. These findings do not support diacerein for treating knee pain in this population.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n Australian New Zealand Clinical Trials Registry:\n ACTRN12618001656224<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamainternmed.2025.8237","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:00:39Z","timestamp":1772467239000},"page":"546","source":"Crossref","is-referenced-by-count":5,"title":["Diacerein for Knee Osteoarthritis"],"prefix":"10.1001","volume":"186","author":[{"given":"Dawn","family":"Aitken","sequence":"first","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Hill","sequence":"additional","affiliation":[{"name":"The Queen Elizabeth Hospital, University of Adelaide, Woodville, South Australia, Australia"},{"name":"Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia M.","family":"Cicuttini","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita E.","family":"Wluka","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen I.","family":"Keen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology School of Medicine and Pharmacology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia"},{"name":"Medical School, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J. W.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"},{"name":"Endocrinology Department, Royal Hobart Hospital, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhavi","family":"Asthana","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny E.","family":"Antony","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Kolling Institute of Medical Research, School of Public Health, University of Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Winzenberg","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"de Graaff","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Buttigieg","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Otahal","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Jones","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"ioi250102r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies.","volume":"29-30","author":"Cui","year":"2020","journal-title":"EClinicalMedicine"},{"issue":"16","key":"ioi250102r2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1001\/jama.2023.19675","article-title":"Evaluation and treatment of knee pain: a review.","volume":"330","author":"Duong","year":"2023","journal-title":"JAMA"},{"issue":"6","key":"ioi250102r3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41584-019-0221-y","article-title":"Therapeutic options for targeting inflammatory osteoarthritis pain.","volume":"15","author":"Conaghan","year":"2019","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"ioi250102r4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1136\/annrheumdis-2014-206676","article-title":"Association between MRI-detected knee joint regional effusion-synovitis and structural changes in older adults: a cohort study.","volume":"75","author":"Wang","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"ioi250102r5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3899\/jrheum.150355","article-title":"Cross-sectional and longitudinal associations between knee joint effusion synovitis and knee pain in older adults.","volume":"43","author":"Wang","year":"2016","journal-title":"J Rheumatol"},{"issue":"4","key":"ioi250102r6","first-page":"753","article-title":"In vitro effects of diacerein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes.","volume":"25","author":"Martel-Pelletier","year":"1998","journal-title":"J Rheumatol"},{"issue":"3","key":"ioi250102r7","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1053\/joca.1998.0201","article-title":"Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures.","volume":"7","author":"Yaron","year":"1999","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"ioi250102r8","doi-asserted-by":"publisher","first-page":"R65","DOI":"10.1186\/ar1028","article-title":"Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti-TNF protocols.","volume":"6","author":"Douni","year":"2004","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"ioi250102r9","doi-asserted-by":"publisher","first-page":"765","DOI":"10.3390\/pharmaceutics13060765","article-title":"Diacerein-loaded hyaluosomes as a dual-function platform for osteoarthritis management via intra-articular injection: in vitro characterization and in vivo assessment in a rat model.","volume":"13","author":"Eladawy","year":"2021","journal-title":"Pharmaceutics"},{"issue":"12","key":"ioi250102r10","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1136\/ard.2003.011742","article-title":"EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).","volume":"62","author":"Jordan","year":"2003","journal-title":"Ann Rheum Dis"},{"issue":"39","key":"ioi250102r11","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035317","article-title":"Efficacy and safety of diacerein and celecoxib combination therapy for knee osteoarthritis: a double-blind, randomized, placebo-controlled prospective study.","volume":"102","author":"Youn","year":"2023","journal-title":"Medicine (Baltimore)"},{"issue":"2","key":"ioi250102r12","article-title":"Diacerein for osteoarthritis.","volume":"2014","author":"Fidelix","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"ioi250102r13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.semarthrit.2019.04.008","article-title":"An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).","volume":"49","author":"Bruy\u00e8re","year":"2019","journal-title":"Semin Arthritis Rheum"},{"issue":"11","key":"ioi250102r15","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"ioi250102r16","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","article-title":"2019 American College of Rheumatology\/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee.","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"ioi250102r17","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1186\/s13063-022-06715-w","article-title":"Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).","volume":"23","author":"Cai","year":"2022","journal-title":"Trials"},{"key":"ioi250102r18","doi-asserted-by":"publisher","first-page":"c332","DOI":"10.1136\/bmj.c332","article-title":"CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials.","volume":"340","author":"Schulz","year":"2010","journal-title":"BMJ"},{"issue":"8","key":"ioi250102r20","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","article-title":"Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee.","volume":"29","author":"Altman","year":"1986","journal-title":"Arthritis Rheum"},{"issue":"3","key":"ioi250102r21","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.joca.2003.11.003","article-title":"Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis.","volume":"12","author":"Peterfy","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"key":"ioi250102r22","doi-asserted-by":"publisher","first-page":"A1","DOI":"10.1016\/j.joca.2006.11.009","article-title":"Atlas of individual radiographic features in osteoarthritis, revised.","volume":"15","author":"Altman","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"ioi250102r23","first-page":"3","article-title":"Atlas of individual radiographic features in osteoarthritis.","volume":"3","author":"Altman","year":"1995","journal-title":"Osteoarthritis Cartilage"},{"issue":"4","key":"ioi250102r24","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/1529-0131(200108)45:4<384::AID-ART352>3.0.CO;2-0","article-title":"Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities.","volume":"45","author":"Angst","year":"2001","journal-title":"Arthritis Rheum"},{"key":"ioi250102r25","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1471-2474-11-80","article-title":"The visual analogue WOMAC 3.0 scale\u2013internal validity and responsiveness of the VAS version.","volume":"11","author":"Kersten","year":"2010","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"ioi250102r26","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.joca.2004.02.001","article-title":"OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.","volume":"12","author":"Pham","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"key":"ioi250102r27","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/acr.24216","article-title":"Adult measures of general health and health-related quality of life.","volume":"72","author":"Busija","year":"2020","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"23","key":"ioi250102r28","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1001\/jama.2024.6063","article-title":"Krill oil for knee osteoarthritis: a randomized clinical trial.","volume":"331","author":"Laslett","year":"2024","journal-title":"JAMA"},{"issue":"4","key":"ioi250102r29","first-page":"685","article-title":"How should we measure medication adherence in clinical trials and practice?","volume":"3","author":"Lee","year":"2007","journal-title":"Ther Clin Risk Manag"},{"issue":"9","key":"ioi250102r30","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: validity of a brief depression severity measure.","volume":"16","author":"Kroenke","year":"2001","journal-title":"J Gen Intern Med"},{"issue":"10","key":"ioi250102r31","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1185\/030079906X132488","article-title":"painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.","volume":"22","author":"Freynhagen","year":"2006","journal-title":"Curr Med Res Opin"},{"issue":"4","key":"ioi250102r32","doi-asserted-by":"crossref","first-page":"R120","DOI":"10.1186\/ar2783","article-title":"The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties.","volume":"11","author":"Bennett","year":"2009","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"ioi250102r33","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/ar3311","article-title":"Distinguishing fibromyalgia from rheumatoid arthritis and systemic lupus in clinical questionnaires: an analysis of the revised Fibromyalgia Impact Questionnaire (FIQR) and its variant, the Symptom Impact Questionnaire (SIQR), along with pain locations.","volume":"13","author":"Friend","year":"2011","journal-title":"Arthritis Res Ther"},{"issue":"11","key":"ioi250102r34","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.joca.2012.07.019","article-title":"Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised controlled trial.","volume":"20","author":"Laslett","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"8","key":"ioi250102r35","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.joca.2017.02.804","article-title":"Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis.","volume":"25","author":"Wang","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"ioi250102r36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: current understanding with therapeutic implications.","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"ioi250102r37","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1136\/ard.2008.099564","article-title":"Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study.","volume":"69","author":"Conaghan","year":"2010","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"ioi250102r38","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/19420862.2015.1026501","article-title":"Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1a and IL-1\u00df.","volume":"7","author":"Lacy","year":"2015","journal-title":"MAbs"},{"issue":"22","key":"ioi250102r39","doi-asserted-by":"crossref","first-page":"8749","DOI":"10.1073\/pnas.83.22.8749","article-title":"Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint.","volume":"83","author":"Pettipher","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"ioi250102r40","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/art.40840","article-title":"A phase II trial of lutikizumab, an anti-interleukin-1a\/\u00df dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis.","volume":"71","author":"Fleischmann","year":"2019","journal-title":"Arthritis Rheumatol"},{"issue":"7","key":"ioi250102r41","doi-asserted-by":"crossref","first-page":"509","DOI":"10.7326\/M20-0527","article-title":"Effects of interleukin-1 beta inhibition on incident hip and knee replacement: exploratory analyses from a randomized, double-blind, placebo-controlled trial.","volume":"173","author":"Schieker","year":"2020","journal-title":"Ann Intern Med"},{"issue":"8","key":"ioi250102r42","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1007\/s10067-024-07042-y","article-title":"Inflammation as a therapeutic target for osteoarthritis: a literature review of clinical trials.","volume":"43","author":"Zhu","year":"2024","journal-title":"Clin Rheumatol"},{"key":"ioi250102r14","unstructured":"The Royal Australian College of General Practitioners. Guideline for the management of knee and hip osteoarthritis. Accessed November 4, 2025. https:\/\/www.racgp.org.au\/FSDEDEV\/media\/documents\/Clinical%20Resources\/Guidelines\/Joint%20replacement\/Guideline-for-the-management-of-knee-and-hip-OA-2nd-edition.pdf"},{"key":"ioi250102r19","unstructured":"European Medicines Agency Pharmacovigilance and Risk Assessment Committee. Assessment report for diacerein containing medicinal products. Accessed June 15, 2022. https:\/\/www.ema.europa.eu\/en\/documents\/referral\/diacerein-article-31-referral-prac-assessment-report_en.pdf"}],"container-title":["JAMA Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/articlepdf\/2845662\/jamainternal_aitken_2026_oi_250102_1777045096.83302.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:00:58Z","timestamp":1777906858000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/fullarticle\/2845662"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamainternmed.2025.8237","relation":{},"ISSN":["2168-6106"],"issn-type":[{"value":"2168-6106","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5,1]]}}}