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      Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis : A Randomized Clinical Trial

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          Key Points

          Question

          What are the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain in patients with osteoarthritis?

          Findings

          In a randomized clinical trial of 140 patients with symptomatic knee osteoarthritis, the use of intra-articular triamcinolone compared with intra-articular saline resulted in greater cartilage volume loss. There was no significant difference on knee pain severity between treatment groups.

          Meaning

          Among patients with symptomatic knee osteoarthritis, intra-articular triamcinolone, compared with intra-articular saline, increased cartilage volume loss and had no effect on knee pain over 2 years.

          Abstract

          Importance

          Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone.

          Objective

          To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain.

          Design, Setting, and Participants

          Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015.

          Interventions

          Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years.

          Main Outcomes and Measures

          Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94).

          Results

          Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm (between-group difference, −0.11 mm; 95% CI, −0.20 to −0.03 mm); and no significant difference in pain (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A 1c levels (between-group difference, −0.2%; 95% CI, −0.5% to −0.007%).

          Conclusions and Relevance

          Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.

          Trial Registration

          ClinicalTrials.gov Identifier: NCT01230424

          Abstract

          This randomized trial compares the effects of intra-articular triamcinolone vs saline injected every 3 months for 2 years on changes in cartilage volume and pain in older adult patients with knee osteoarthritis.

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          Author and article information

          Journal
          JAMA
          JAMA
          JAMA
          JAMA
          American Medical Association
          0098-7484
          1538-3598
          16 May 2017
          16 May 2017
          16 November 2017
          : 317
          : 19
          : 1967-1975
          Affiliations
          [1 ]Division of Rheumatology, Tufts Medical Center, Boston, Massachusetts
          [2 ]Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
          [3 ]Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts
          [4 ]Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts
          [5 ]Division of Musculoskeletal Imaging and Intervention, Tufts Medical Center, Boston, Massachusetts
          Author notes
          Article Information
          Corresponding Author: Timothy E. McAlindon, DM, MPH, Division of Rheumatology, Tufts Medical Center, 800 Washington St, PO Box 406, Boston, MA 02111 ( tmcalindon@ 123456tuftsmedicalcenter.org ).
          Accepted for Publication: April 12, 2017.
          Author Contributions: Dr McAlindon had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
          Concept and design: McAlindon, LaValley, Zhang.
          Acquisition, analysis, or interpretation of data: All authors.
          Drafting of the manuscript: McAlindon, LaValley, Harvey, Price, Zhang.
          Critical revision of the manuscript for important intellectual content: All authors.
          Statistical analysis: McAlindon, LaValley, Price, Zhang.
          Obtained funding: McAlindon.
          Administrative, technical, or material support: Harvey, Driban, Ward.
          Supervision: McAlindon, Harvey.
          Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
          Funding/Support: This study was supported by grants R01 AR051361 from the National Institute for Arthritis and Musculoskeletal Disorders and Skin Diseases (NIAMS) and UL1TR001064 from the National Center for Advancing Translational Sciences, National Institutes of Health.
          Role of the Funder/Sponsor: The funding sponsors played no part in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript or decision to submit for publication. Sponsors had no access to the data and did not perform any of the study analysis.
          Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
          Additional Contributions: We thank the participants who made this study possible; also the following professionals for their uncompensated help with this study: Gayle Lester, PhD, NIAMS, for guidance and advice, Eric Miller, PhD, Tufts University School of Engineering, for image analysis advice, and the data and safety monitoring board members (Joanne Jordan, MD, Kenneth Kalunian, MD, Charles H. Goldsmith, PhD; Liana Fraenkel, MD, MPH) for their assistance with and oversight of this trial; and Amanda Canavatchel, BS, Tufts Medical Center, for help in preparation of the manuscript.
          Article
          PMC5815012 PMC5815012 5815012 joi170044
          10.1001/jama.2017.5283
          5815012
          28510679
          6d8a9ba5-f4cf-4cfa-bee8-c6f4e0010f36
          Copyright 2017 American Medical Association. All Rights Reserved.
          History
          : 7 October 2016
          : 7 April 2017
          : 12 April 2017
          Funding
          Funded by: National Institute for Arthritis and Musculoskeletal Disorders and Skin Diseases
          Funded by: National Center for Advancing Translational Sciences
          Categories
          Research
          Research
          Original Investigation
          Featured

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