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.
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.
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 compare the mean change in VAS score after intra-articular injection of Hyaluronic acid and Steroids in patients with initial stages of knee osteoarthritis. Study Design: Randomized controlled trail study. Place and Duration of Study: This study was conducted at the department of Orthopedics, BVH Bahawalpur from September 2017 to February 2018. Materials and Methods: To compare the mean change in VAS score after intra-articular injection of Hyaluronic acid and Steroids in patients with initial stages of knee osteoarthritis Results: The mean age in group A was 59.55 ± 7.60 years and group B 59.37 ± 8.26 years. Out of these 80 patients, 52 (65.0%) were females and 28 (35.0%) males with 1.85:1 female-male ratio. Mean pre-treatment VAS score in group A was 6.30 ± 1.38 while in group B was 5.95 ± 1.50. Mean post-treatment VAS score in group A was 4.48 ± 1.26 while in group B was 1.60 ± 0.93. Mean reduction in VAS score in group A was 1.82 ± 0.12 while in group B was 4.35 ± 0.57. Conclusion: We recommend hyaluronic acid in patients with initial stages of knee OA because significant reduction in mean VAS score (at 6 months) observed with intra-articular hyaluronic acid as compared to corticosteroid use.
ABSTRACT: OBJECTIVE: Although intra-articular corticosteroid injections are widely applied in the treatment of knee osteoarthritis (OA), its effect is short term. Additionally, apart from oral use, tenoxicam is also applied as an intra-articular treatment option to minimize gastrointestinal side effects of NSAIDs. Clinical evidence suggests that the combined use of NSAIDs and corticosteroids is synergistic (especially macular edema after cataract surgery in ophthalmology). Therefore, the aim of this study is to determine whether the combination of intra-articular steroid and tenoxicam was more effective for a long period rather than only tenoxicam and steroid injection alone in OA treatment.
METHODS: Ninety patients were randomly divided into three groups (30 patients per group): group 1, group 2, and group 3 were treated by intra-articular injection of tenoxicam, triamcinolone hexacetonide, and triamcinolone hexacetonide plus tenoxicam, respectively. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were enrolled at baseline and 1, 3, and 6 months post-injection.
RESULTS: The mean age of patients was 68.07 ± 8.08, 65.83 ± 10.13, and 67.07 ± 6.01 in group 1, group 2, and group 3, respectively. In tenoxicam group, median pre- and post-treatment (at 1, 3, and 6 months) VAS/WOMAC scores were 7.30 ± 0.53/32.50 ± 3.79, 2.27 ± 0.98/10.83 ± 2.61, 6.73 ± 1.14/30.33 ± 5.93, and 7.03 ± 0.80/31.37 ± 4.38, respectively. In steroid group, median pre- and post-treatment VAS/WOMAC scores were 7.60 ± 0.49/34.33 ± 3.40, 1.37 ± 1.21/8.83 ± 2.70, 6.87 ± 1.35/30.80 ± 7.70, and 7.27 ± 0.86/32.83 ± 4.87, respectively. In steroid plus tenoxicam group, median pre- and post-treatment VAS/WOMAC scores were 7.57 ± 0.50/33.20 ± 3.66, 0.33 ± 0.47/6.67 ± 0.95, 0.93 ± 0.98/7.87 ± 1.96, and 1.97 ± 1.12/10.43 ± 3.70, respectively. VAS and WOMAC scores in 1 month after the injection significantly decreased in both groups compared to baseline (p < 0.01). Steroid plus tenoxicam group showed significantly improved VAS and WOMAC scores when compared to only steroid and tenoxicam group at follow-up 3 and 6 months (p < 0.01).
CONCLUSION: The combined therapy seems to produce a more effective result for a long period than monotherapy in reducing pain and improving functional recovery.
KEY POINTS: • There is an evidence of short-term effects of intra-articular corticosteroid injection in treatment of knee OA; however, there is no consensus for the long-term benefit of this treatment yet. • Apart from oral use, tenoxicam is also applied as an intra-articular treatment option to minimize gastrointestinal side effects of NSAIDs. • Clinical evidence suggests that the combined use of NSAIDs and corticosteroids is synergistic (especially macular edema after cataract surgery in ophthalmology). • The combined therapy seems to produce a more effective result for a long period than alone therapy.
BACKGROUND: Intra-articular corticosteroids are commonly used for pain relief in patients with knee osteoarthritis. Simultaneous intra-articular corticosteroid (CS) knee injections may be beneficial for the ~80-90% of patients who present with, or develop, bilateral knee osteoarthritis, but concurrent injections may increase systemic CS exposure and data on safety/tolerability are lacking. Triamcinolone acetonide extended release (TA-ER) has shown decreased systemic triamcinolone acetonide exposure compared with traditional triamcinolone acetonide crystalline suspension (TAcs) after a single knee injection in patients with knee osteoarthritis. This phase IIa study was designed to assess the safety and systemic triamcinolone acetonide exposure following injections of TA-ER or TAcs into each knee of patients with bilateral knee osteoarthritis.
METHODS: Patients (⩾40 years) meeting American College of Rheumatology criteria for knee osteoarthritis in both knees received concurrent single intra-articular injections of TA-ER 32 mg or TAcs 40 mg into each knee (total: 64 mg and 80 mg, respectively) and were followed for 6 weeks. Safety was evaluated based on treatment-emergent adverse events (TEAEs). Blood samples for pharmacokinetic analysis were collected pre-injection, and at the following postinjection time points: 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h, and days 8, 15, 29, and 43.
RESULTS: Baseline characteristics were balanced between patients randomly assigned to TA-ER (n = 12) or TAcs (n = 12). Both treatments were well tolerated with comparable TEAE profiles. Peak plasma triamcinolone acetonide concentrations (Cmax) were lower following bilateral TA-ER injections [geometric mean, 2277.7 pg/ml (95% CI, 1602.13-3238.04)] compared with bilateral TAcs injections [7394.7 pg/ml (2201.06-24,843.43)], with median times to Cmax (Tmax) of 4.5 and 6.5 h, respectively.
CONCLUSIONS: In patients with bilateral knee osteoarthritis, intra-articular injection of TA-ER into both knees was well tolerated. Consistent with pharmacokinetic profiles observed after a single knee injection, plasma triamcinolone acetonide concentrations were lower after bilateral TA-ER injections compared with the higher and more variable concentrations observed after bilateral TAcs injections.
CLINICALTRIALSGOV IDENTIFIER: NCT03378076.
OBJECTIVE: To compare the effect of two different corticosteroid regimens methylprednisolone acetate and triamcenolone acetate in bilateral and symmetrical knee osteoarthritis (OA) pain relief. STUDY DESIGN: A Randomize Control Trial study. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Anaesthesia, Intensive care and Pain Management, Hameed Latif Hospital, Lahore from 1st November 2016 to 30th October 2017. MATERIALS AND METHODS: After getting ethical approval from hospital ethical committee and informed consent from patients to be included in study. Total 100 patients were enrolled in study through non probability consecutive sampling technique, and all patients were divided in two equal groups randomly using lottery method. Data was collected on pre designed Performa. Statistical analysis was done by using SPSS version 24 for all variables, mean and SD presentation for continuous data like age and VAS score, WOMAC score and frequency percentage presentation was given for categorical data like gender. P value <0.05 was considered as significant. RESULTS: Total 100 patients were included, in this study. The mean age and BMI of the patients was 60.33±2.61 years and 27.06±2.42 kg/m2 respectively. A significant decrease in VAS score for both knees (right and left) was observed after intra articular injection bilaterally. Measurements were done at 2, 4, 8, 12 and 24 weeks after injection administration (p<0.005). CONCLUSION: Results of our study revealed that intra articular injection is an effective mode of treatment when used for the management of osteoarthritis knee pain (p<0.005). When we compared two steroid regimens Methylprednisolone and Triamcenolone it was observed that there is no significant difference among both groups, both are equally effective.
Objective: FX006 is a novel, microsphere-based, extended-release formulation of triamcinolone acetonide for intraarticular (IA) injection designed to maintain treatment concentration in the joint and provide prolonged analgesic benefits in patients with osteoarthritis (OA) of the knee. This study was undertaken to compare the analgesic benefits of 2 FX006 doses with saline placebo injection. Methods: In this phase IIb study, participants with knee OA (Kellgren/Lawrence grade 2–3) and average daily pain (ADP) intensity ≥5 to ≤9 (on a 0–10 Numerical Rating Scale) were randomized (1:1:1) to receive single IA injections of FX006 32 mg (n = 104) or 16 mg (n = 102) or saline placebo (n = 100). The primary end point was the least squares mean (LSM) change from baseline to week 12 in weekly mean ADP intensity scores for FX006 32 mg versus saline placebo. Results: The primary end point was not met (LSM change at week 12 −3.1 with FX006 32 mg versus −2.5 with saline placebo; LSM difference [95% confidence interval] −0.58 [−1.22, 0.07]) (P = 0.08). However, improvements in ADP intensity were significantly greater with FX006 32 mg than saline placebo at weeks 1–11 and week 13. Improvements in ADP intensity were significantly greater with FX006 16 mg versus saline placebo at weeks 1–9. A dose-response effect in duration of maximal analgesic effect was evident (13 weeks with 32 mg versus 9 weeks with 16 mg), with FX006 32 mg providing increased therapeutic benefit relative to FX006 16 mg. All treatments were well tolerated. Conclusion: Although the primary end point was not met, our findings indicate a prolonged reduction in symptoms with FX006 with an evident dose response and a safety profile similar to saline placebo.
<b>BACKGROUND: </b>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.<b>METHODS: </b>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.<b>RESULTS: </b>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.<b>CONCLUSIONS: </b>FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point).<b>LEVEL OF EVIDENCE: </b>Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Background Knee pain is one of the common complaints patients present with in any community based health camps and Osteoarthritis of knee is a usual diagnosis. Injecting a long acting steroid is a common practice to alleviate the symptoms of osteoarthritic knee. Objective To evaluate the clinical outcome of injecting Triamcinolone acetenoid in osteoarthritis of knee in a community set up over a randomized double-blind placebo control trial. Method A prospective, randomized, double blind, placebo control trial was carried out in community after obtaining the ethical clearance from the IRC. Patients with clinically diagnosed osteoarthritis of knee were injected either Triamcinolone or Placebo after recording the baseline scores of the knee by Knee injury and Osteoarthritis Outcome Score (KOOS) - Physical Function Short form (KOOS-PS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS). The same tools were used at two, six and at twelve weeks post injection to evaluate the functional outcome and pain. Result One hundred and seventeen patients were available for analysis among which, 55(48.7%) patients received Triamcinolone and 58(51.3%) received placebo. The baseline status of knees of two groups was comparable at the start of study. There was significant pain relief in the group receiving Triamcinolone at two and six week but not in twelve weeks. Group receiving placebo had pain relief only for first two weeks. Functional outcome was significantly improved compared to baseline in both the groups until six weeks however, in the triamcinolone group, it was significant until twelve weeks. No major complications were noted. Conclusion Intra-articular injection of Triamcinolone acetenoid is effective in symptoms control and improving functional outcome in clinically diagnosed osteoarthritis of knees in community set up during health camps.
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.
