BACKGROUND: Intra-articular (IA) corticosteroid injection is recommended in refractory knee osteoarthritis patients. However, 40-mg of triamcinolone IA every 3 months for 2 years reduces cartilage volume as compared to saline IA.
OBJECTIVE: To determine the non-inferiority of 10-mg versus 40-mg of triamcinolone acetonide (TA) for treatment of pain in symptomatic knee osteoarthritis at week 12.
METHODS: This was a double-blind, randomized, controlled trial conducted in 84 symptomatic knee osteoarthritis patients. The 10-mg or 40-mg of TA were 1:1 randomized and injected to the affected knees. The primary outcome was the 12-week difference from baseline in pain VAS, with a pre-specified lower margin for non-inferiority of 10 mm. The measuring instruments used were: Visual analog scale (VAS: 0-10), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Group 5 Dimensions (EQ5D), Knee Injuries and Osteoarthritis Outcome Score (KOOS) questionnaire, chair standing test and 20-m walking time at baseline, at week 4, and week 12 after randomization. Adverse events were recorded.
RESULTS: Baseline characteristics were similar between two groups. The mean differences of pain VAS (95% confidence interval: CI) between the two groups at baseline and week 12 were 0.8 (-0.8, 2.4) with p of 0.002 for non-inferiority. There were no differences in pain reduction and quality of life improvement between 10-mg and 40-mg groups. The mean differences (95%CI) of WOMAC, KOOS pain, EQ5D and KOOS quality of life between baseline and week 12 were 0.4 (-1.1, 1.9). -8.7 (-21.3, 3.9), 1.3(-7.1, 9.6) and 1.8 (-11.5, 15.0), respectively. There were significant improvements in pain and quality of life between baseline and week 12 in both groups.
CONCLUSION: The 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. Both 10 mg and 40 mg of TA significantly improved pain and quality of life in patients with symptomatic knee OA.
TRIAL REGISTRATION: TCTR, I TCTR20210224002. Retrospectively registered 24 February 2021, http://www.thaiclinicaltrials.org/show/TCTR20210224002.
OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA).
METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors.
RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment.
CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.
INTRODUCTION: Intra-articular (IA) corticosteroids, including triamcinolone acetonide (TA), are a recommended treatment for hip osteoarthritis. We compared the safety and systemic exposure of TA extended-release (TA-ER) versus TA crystalline suspension (TAcs) in patients with hip osteoarthritis.
METHODS: In this phase 2, randomized, multicenter, open-label, single-dose study (NCT03382262), patients with hip osteoarthritis were randomly assigned 1:1 to receive single IA injections of TA-ER 32 mg or TAcs 40 mg. Safety assessments included treatment-emergent adverse events (TEAEs). Blood samples were collected for pharmacokinetic (PK) analysis up to day 85. PK parameters included area under the concentration-time curve, total body drug clearance, maximum concentration (Cmax), mean residence time, half-life, and time to maximum concentration.
RESULTS: Of 30 patients (TA-ER: n = 15; TAcs: n = 15) randomized and included in the Safety Population, 25 patients were evaluated in the PK Population. TEAEs were reported in four of 15 (26.7%) patients who received TA-ER and in seven of 15 (46.7%) patients who received TAcs. The most common TEAEs included arthralgia and headache. All TEAEs were of grade 1 or 2 in severity. TA-ER produced substantially lower peak plasma TA concentrations compared with TAcs (Cmax geometric mean: 890.4 vs. 5549.4 pg/ml), and these were less variable with TA-ER versus TAcs. Similarly, overall TA systemic exposure was substantially lower for TA-ER versus TAcs, with gradual elimination from systemic circulation through day 85.
CONCLUSIONS: Following a single IA injection in the hip, TA-ER was generally well tolerated, with a safety profile comparable to that of TAcs. Systemic TA exposure was markedly lower in TA-ER-treated patients, consistent with the PK profile observed in knee osteoarthritis.
CLINICALTRIALS: gov identifier: NCT03382262.
<b>PURPOSE: </b>To assess the safety and efficacy of genicular artery embolization (GAE) compared with a sham procedure in the treatment of knee pain secondary to mild to moderate osteoarthritis (OA).<b>MATERIALS AND METHODS: </b>A multicenter, single-blinded, randomized controlled trial was conducted to evaluate knee OA symptom reduction after GAE versus sham procedure. Subjects (n = 21) with mild to moderate OA and intractable knee pain were randomized 2:1 to either GAE or a sham procedure. Subjects who were randomized to the sham procedure and did not report clinical improvement in both the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores were unblinded and able to crossover to treatment at 1 month. Longitudinal data were collected for 12 months, and subjects were excluded if they required additional analgesics at follow-up. Reductions in the VAS and total WOMAC scores were compared using mixed-effects linear regression models.<b>RESULTS: </b>All subjects in the sham group failed to show significant improvements at 1 month and crossed over to the treatment arm. There was a statistically significantly greater pain reduction in the treatment group than in the sham group at 1 month (VAS, 50.1 mm; standard error [SE], 10.6; 95% confidence interval [CI], 29.0, 72.3; P<.01). Disability improvement was also significantly greater in the treatment group (WOMAC, 24.7 points; SE, 10.4; 95% CI, 3.5, 45.9; P=.02). Only minor adverse events were reported. Five subjects were excluded after increased analgesic use. Sensitivity analysis with all excluded patients confirmed significant improvements at 1 and 12 months.<b>CONCLUSION: </b>In patients with mild to moderate knee OA, GAE results in symptomatic improvement greater than the sham procedure with clinically significant reduction in pain and disability.
PURPOSE: Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres.
METHODS: Thirty-eight patients, median age = 60 (45-83), attended for GAE using 100-300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0-100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively.
RESULTS: Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53-66) at baseline to 36 (SD = 24, 95% CI 28-44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30-60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis.
CONCLUSION: GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.
BACKGROUND AND OBJECTIVES: Osteoarthritis (OA) is a major public health burden. While knee and hip joints are most commonly affected, the glenohumoral (shoulder) joint is also frequently involved. We evaluated the pharmacokinetics and safety/tolerability of triamcinolone acetonide extended-release (TA-ER) and triamcinolone acetonide crystalline suspension (TAcs) in patients with shoulder OA.
METHODS: In this phase 2, randomized, open-label, single-dose study (NCT03382262), adults with moderately-to-severely symptomatic shoulder OA for ≥ 6 months randomly received a single ultrasound-guided intra-articular (IA) injection of TA-ER 32 mg or TAcs 40 mg. Safety was evaluated throughout 12 weeks post-injection; blood samples for pharmacokinetic evaluations were collected pre-injection and through Day 85 post-injection.
RESULTS: Among 25 randomized patients, 12 received TA-ER and 13 received TAcs. Most patients were female (60%), and all had moderate (72%) or severe (28%) shoulder OA. Adverse events (AEs) were reported by four (33%) patients following TA-ER and three (23%) following TAcs injection. No AE was serious or led to study discontinuation. Systemic exposure following TAcs was approximately 1.5-fold higher than that following TA-ER injection (geometric mean [GM] AUC0-last 873,543 vs 557,602 h × pg/mL). GM Cmax was also higher in TAcs- than TA-ER-treated patients (2034 vs 1283 pg/mL). Bioequivalence testing confirmed lower systemic TA exposure following TA-ER than TAcs IA injection.
CONCLUSION: These pharmacokinetic data confirm protracted release of TA from TA-ER following IA injection in patients with shoulder OA. Lower peak and systemic TA exposure following TA-ER suggests TA-ER could potentially confer an improved systemic safety profile over TAcs.
TRIAL REGISTRATION NUMBER: NCT03382262 (December 22, 2017 retrospectively registered).
OBJECTIVE: To investigate the associations between clinical, procedural, and radiographic factors and outcomes of steroid hip injections, including long-term and immediate pain reduction, time to arthroplasty, time to reinjection, and the total number of injections.
MATERIALS AND METHODS: All intra-articular anesthetic and steroid injections of the hip under fluoroscopic guidance between January 2014 and March 2016 were retrospectively reviewed. Hip radiographs were scored using the Kellgren-Lawrence (KL) and Osteoarthritis Research Society International (OARSI) scores. Immediate pain relief and response were evaluated using a change in visual analog scale and OMERACT-OARSI criteria respectively. Long-term pain relief was evaluated at 2‑7 months after injection by reviewing the medical records. Correlation between patient characteristics, procedural variations, and radiographic factors with injection outcomes was analyzed by using linear and logistic regression models.
RESULTS: Of 361 injections, 79.8% showed an immediate pain response and 32.7% had subjective long-term pain relief (> 2 months). There was no significant correlation between immediate pain relief and response with long-term pain relief and other outcomes. Older age and higher KL score, OARSI-central joint space narrowing (JSN), and inferior acetabular osteophyte were correlated with long-term pain relief (p = 0.01‑0.03). Higher KL and OARSI grades, particularly JSN, were significantly correlated with increased immediate pain relief and total number of injections but decreased time to arthroplasty. Baseline pain positively correlated with immediate pain response (p < 0.001).
CONCLUSIONS: Older patients with higher grades of radiographic OA and high baseline pain were good candidates for steroid injections, particularly for those patients awaiting hip arthroplasty.
Various systematic reviews have recently shown that intra-articular platelet-rich plasma (IA-PRP) can lead to symptomatic relief of knee osteoarthritis for up to 12 months. There exist limited data on its use in small joints, such as the trapeziometacarpal joint (TMJ) or carpometacarpal joint (CMCJ) of the thumb. A prospective, randomized, blind, controlled, clinical trial of 33 patients with clinical and radiographic osteoarthritis of the TMJ (grades: I-III according to the Eaton and Littler classification) was conducted. Group A patients (16 patients) received 2 ultrasound-guided IA-PRP injections, while group B patients (17 patients) received 2 ultrasound-guided intra-articular methylprednisolone and lidocaine injections at a 2-week interval. Patients were evaluated prior to and at 3 and 12 months after the second injection using the visual analogue scale (VAS) 100/100, shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (Q-DASH), and patient's subjective satisfaction. No significant differences between the baseline clinical and demographic characteristics of the 2 groups were identified. After 12 months' follow-up, the IA-PRP treatment has yielded significantly better results in comparison with the corticosteroids, in terms of VAS score (P = 0.015), Q-DASH score (P = 0.025), and patients' satisfaction (P = 0.002). Corticosteroids offer short-term relief of symptoms, but IA-PRP might achieve a lasting effect of up to 12 months in the treatment of early to moderate symptomatic TMJ arthritis.
PURPOSE: To evaluate the efficacy and safety of embolization of hyperemic synovial tissue for the treatment of knee pain secondary to osteoarthritis (OA).
MATERIALS AND METHODS: Twenty patients with radiographic knee OA and moderate-to-severe pain refractory to conservative therapy were enrolled in a prospective, 2-site pilot study. Genicular artery embolization (GAE) was performed with 75- or 100-μm spherical particles. Patients were assessed with magnetic resonance imaging at baseline and at 1 month and with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, and 6 months. Adverse events were recorded at all timepoints.
RESULTS: Embolization of at least 1 genicular artery was achieved in 20/20 (100%) patients. Mean VAS improved from 76 mm ± 14 at baseline to 29 mm ± 27 at 6-month follow-up (P < .01). Mean WOMAC score improved from 61 ± 12 at baseline to 29 ± 27 at 6-month follow-up (P < .01). Self-limiting skin discoloration occurred in 13/20 (65%) patients. Two of 20 (10%) patients developed plantar sensory paresthesia that resolved within 14 days.
CONCLUSIONS: GAE to treat knee pain secondary to OA can be performed safely and demonstrates potential efficacy. Further randomized comparative studies are needed to determine true treatment effect versus placebo effect.
<b>BACKGROUND: </b>Both physical therapy and intraarticular injections of glucocorticoids have been shown to confer clinical benefit with respect to osteoarthritis of the knee. Whether the short-term and long-term effectiveness for relieving pain and improving physical function differ between these two therapies is uncertain.<b>METHODS: </b>We conducted a randomized trial to compare physical therapy with glucocorticoid injection in the primary care setting in the U.S. Military Health System. Patients with osteoarthritis in one or both knees were randomly assigned in a 1:1 ratio to receive a glucocorticoid injection or to undergo physical therapy. The primary outcome was the total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 1 year (scores range from 0 to 240, with higher scores indicating worse pain, function, and stiffness). The secondary outcomes were the time needed to complete the Alternate Step Test, the time needed to complete the Timed Up and Go test, and the score on the Global Rating of Change scale, all assessed at 1 year.<b>RESULTS: </b>We enrolled 156 patients with a mean age of 56 years; 78 patients were assigned to each group. Baseline characteristics, including severity of pain and level of disability, were similar in the two groups. The mean (±SD) baseline WOMAC scores were 108.8±47.1 in the glucocorticoid injection group and 107.1±42.4 in the physical therapy group. At 1 year, the mean scores were 55.8±53.8 and 37.0±30.7, respectively (mean between-group difference, 18.8 points; 95% confidence interval, 5.0 to 32.6), a finding favoring physical therapy. Changes in secondary outcomes were in the same direction as those of the primary outcome. One patient fainted while receiving a glucocorticoid injection.<b>CONCLUSIONS: </b>Patients with osteoarthritis of the knee who underwent physical therapy had less pain and functional disability at 1 year than patients who received an intraarticular glucocorticoid injection. (ClinicalTrials.gov number, NCT01427153.).
Intra-articular (IA) corticosteroid injection is recommended in refractory knee osteoarthritis patients. However, 40-mg of triamcinolone IA every 3 months for 2 years reduces cartilage volume as compared to saline IA.
OBJECTIVE:
To determine the non-inferiority of 10-mg versus 40-mg of triamcinolone acetonide (TA) for treatment of pain in symptomatic knee osteoarthritis at week 12.
METHODS:
This was a double-blind, randomized, controlled trial conducted in 84 symptomatic knee osteoarthritis patients. The 10-mg or 40-mg of TA were 1:1 randomized and injected to the affected knees. The primary outcome was the 12-week difference from baseline in pain VAS, with a pre-specified lower margin for non-inferiority of 10 mm. The measuring instruments used were: Visual analog scale (
VAS:
0-10), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Group 5 Dimensions (EQ5D), Knee Injuries and Osteoarthritis Outcome Score (KOOS) questionnaire, chair standing test and 20-m walking time at baseline, at week 4, and week 12 after randomization. Adverse events were recorded.
RESULTS:
Baseline characteristics were similar between two groups. The mean differences of pain VAS (95% confidence interval: CI) between the two groups at baseline and week 12 were 0.8 (-0.8, 2.4) with p of 0.002 for non-inferiority. There were no differences in pain reduction and quality of life improvement between 10-mg and 40-mg groups. The mean differences (95%CI) of WOMAC, KOOS pain, EQ5D and KOOS quality of life between baseline and week 12 were 0.4 (-1.1, 1.9). -8.7 (-21.3, 3.9), 1.3(-7.1, 9.6) and 1.8 (-11.5, 15.0), respectively. There were significant improvements in pain and quality of life between baseline and week 12 in both groups.
CONCLUSION:
The 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. Both 10 mg and 40 mg of TA significantly improved pain and quality of life in patients with symptomatic knee OA.
TRIAL REGISTRATION:
TCTR, I TCTR20210224002. Retrospectively registered 24 February 2021, http://www.thaiclinicaltrials.org/show/TCTR20210224002.
