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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.

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 A1c 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.

SUBMITTER: McAlindon TE

PROVIDER: S-EPMC5815012 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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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.

McAlindon Timothy E TE LaValley Michael P MP Harvey William F WF Price Lori Lyn LL Driban Jeffrey B JB Zhang Ming M Ward Robert J RJ

JAMA 20170501 19

<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>Two-y ...[more]

PMID: 28510679

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Project description:ImportanceMost clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.ObjectiveTo evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.Design, setting, and participantsThis randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.InterventionsInterventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).Main outcomes and measuresThe 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.ResultsAmong 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.Conclusions and relevanceAmong patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.Trial registrationAustralian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347.

Project description:Background: Knee Osteoarthritis (kOA), the most common joint degenerative disorder, lacks effective therapeutics. Placenta-derived mesenchymal stromal cells (PMSCs) are effective in tissue repairing and generation, which have potential in treating kOA. This study aimed to determine the anti-kOA efficacy of PMSCs and to explore its action mode. Methods: Flow cytometry and three-line differentiation were performed for identification of PMSCs. In vivo, a rat kOA model established by anterior cruciate ligament transection (ACLT) surgery was used to evaluate the efficacy of PMSCs. Histopathological HE and SO staining with Osteoarthritis Research Society International scoring were conducted, and cartilage expressions of MMP13 and Col2 were measured by immunohistochemistry. Pain behavior parameters by mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), were measured. In vitro, wound healing and cell immunofluorescence assays were conducted to detect the proliferation and migration ability of chondrocytes treated with PMSCs conditioned medium (PMSCs-CM). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) assays were applied to explore the molecular action of PMSCs on chondrocytes. Results: The results of flow cytometry indicated that the surface markers of PMSCs (CD73 > 95%, CD90 > 95%, and CD34 < 2%) were consistent with the typical mesenchymal stromal cells. The in vivo data showed that PMSCs significantly reversed the kOA progression by protection of cartilage, regulation of anabolic (Col2) and catabolic (MMP13) expressions, and relief of pain symptoms. The in vitro data showed that PMSCs promoted chondrocyte proliferation and migration and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Mmp13, Adamts4, Adamts5 and Sox9 and also restored the abnormal protein expressions of Col2, Mmp13 and Sox9 of chondrocytes. The molecular actions of PMSCs on chondrocytes in nested co-culture way or in conditioned medium way were similar, confirming a paracrine-based mode of action. Conclusion: This study demonstrated PMSCs' anti-kOA efficacy and its paracrine-based action mode, providing novel knowledge of PMSCs and suggesting it as a promising cell therapy for treatment of kOA.

Project description:ImportanceIntra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.ObjectiveTo investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care.Design, setting, and participantsThe KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020.InterventionsPatients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks.Main outcomes and measuresThe pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis.ResultsA total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1 to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious.Conclusions and relevanceBased on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections.Trial registrationDutch Trial Registry: NTR6968.

Project description:BACKGROUND:Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. METHODS:In this Phase-3, multicenter, double-blinded, 24-week study, adults ?40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ?5 and ?9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. RESULTS:The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ?50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ? 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. CONCLUSIONS:FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point). LEVEL OF EVIDENCE:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Project description:ObjectiveWhile the effect of triamcinolone acetonide extended-release (TA-ER) on reducing knee osteoarthritis (OA) pain has been reported, the effects on physical performance are incompletely understood. This open label clinical trial systematically evaluated the effects of intra-articular TA-ER on physical performance, self-reported function, and quality of life in participants with bilateral symptomatic knee OA 6, 12 (primary) and 24 weeks following bilateral injection of TA-ER (32 mg).MethodsSeventy participants were enrolled (61.4% women; age 64.0 ± 11.7; BMI 31.8 ± 5.7 kg/m2). Physical performance was measured by 30-s chair stand test, 40 m fast paced walk test (FPWT), and stair negotiation test at baseline and each follow-up visit. Physical function and quality of life (QOL) were measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) and pain was measured with numeric rating scale (NRS).ResultsIn comparison with baseline, self-reported pain, function, and quality of life were improved at each follow-up through 24 weeks and the number of chair-stands significantly improved following treatment by (mean ± SE) 1.9 ± 0.6 at 6-week (p = 0.0048) and by 1.8 ± 0.5 at 12-week follow-up (p = 0.0011) but was not statistically significant at 24-week follow-up (0.6 ± 0.6; p = 0.4711). Stair negotiation times were 7.2 ± 3.7, 7.1 ± 3.8, and 5.4 ± 4.0 s lower at the three respective follow-up timepoints, although these changes did not reach statistical significance (p = 0.0530, p = 0.0599, and p = 0.1793 respectively). The 40m-FPWT time did not significantly improve.ConclusionThese data indicate improvement in chair stand performance through 12 weeks post-injection and sustained improvement in participant-reported physical function through 24-week follow-up in adults with bilateral painful knee OA treated with TA-ER.

Project description:BackgroundCartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation.PurposeTo evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model.Study designControlled laboratory study.MethodsA full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mice (N = 80). Mice received an intra-articular injection of TAA or saline on day 1 or 7 after induction of the defect. Mice were euthanized on days 10 and 28 for histological evaluation of cartilage defect repair, synovial inflammation, and synovial membrane thickness.ResultsMice injected with TAA had significantly less synovial inflammation at day 10 than saline-injected mice independent of the time of administration. At day 28, the levels of synovitis dropped toward healthy levels; nevertheless, the synovial membrane was thinner in TAA- than in saline-injected mice, reaching statistical significance in animals injected on day 1 (70.1 ± 31.9 µm vs 111.9 ± 30.9 µm, respectively; P = .01) but not in animals injected on day 7 (68.2 ± 21.86 µm vs 90.2 ± 21.29 µm, respectively; P = .26). A thinner synovial membrane was moderately associated with less filling of the defect after 10 and 28 days (r = 0.42, P = .02; r = 0.47, P = .01, respectively). Whereas 10 days after surgery there was no difference in the area of the defect filled and the cell density in the defect area between saline- and TAA-injected knees, filling of the defect at day 28 was lower in TAA- than in saline-injected knees for both injection time points (day 1 injection, P = .04; day 7 injection, P = .01). Moreover, there was less collagen type 2 staining in the filled defect area in TAA- than in saline-injected knees after 28 days, reaching statistical significance in day 1-injected knees (2.6% vs 18.5%, respectively; P = .01) but not in day 7-injected knees (7.4% vs 15.8%, respectively; P = .27).ConclusionIntra-articular injection of TAA reduced synovial inflammation but negatively affected cartilage repair. This implies that inhibition of inflammation may inhibit cartilage repair or that TAA has a direct negative effect on cartilage formation.Clinical relevanceOur findings show that TAA can inhibit cartilage defect repair. Therefore, we suggest not using TAA to reduce inflammation in a cartilage repair setting.

Dataset Information

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

Publications

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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