Intra-articular triamcinolone hexacetonide injections in hands osteoarthritis ‒ A double-blinded randomized controlled trial with a one year follow-up.

OBJECTIVE: to evaluate the effectiveness of triamcinolone Hexacetonide (TH) Intra-Articular Injection (IAI) in hand Interphalangeal Joints (IP) of Osteoarthritis (OA) patients to improve pain and joint swelling; improve function, goniometry, and grasping force, and assess IAI influence on radiographic evolution over 1-year. METHODS: A randomized, double-blind study. 60 patients who underwent IAI at the most symptomatic IP joint were randomly assigned to receive TH+Lidocaine (LD) (TH/LD group) or just LD (LD group). Patients were assessed blindly for 1-year, at baseline and 1, 4, 8, 12, and 48 weeks. The following variables were assessed: articular pain and swelling, AUSCAN and COCHIN functional questionnaires, grip and pinch strength, goniometry, perception of improvement, acetaminophen consumption, and simple radiography. Repeated-measures ANOVA test was used to analyze the intervention response. RESULTS: Sixty patients completed the follow-up. There were nine missed assessments. 97% were women; mean age of 61-years (SD = 8.2), and approximately 5-years of disease (SD = 3.6). Half of the patients present radiographic classification Kellgren and Lawrence (KL) grades I and II, and the other half grades III and IV. The two groups evolved similarly at 48-weeks. TH/LD group had a better evaluation in joint swelling and acetaminophen consumption (p = 0.04 and p < 0.001, respectively) at 48-weeks. Radiographically there was no statistical difference between groups (KL, p = 0.564; erosive OA, p = 0.999; worsening, p = 0.573). CONCLUSION: The IAI IP hands OA is effective for the improvement of joint swelling and decrease of analgesic consumption and does not influence the radiographic evolution of the injected joint.

Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: A double blinded randomized controlled trial with one year follow-up.

OBJECTIVES: To compare the effectiveness of intra-articular injection (IAI) of Platelet-Rich Plasma (PRP) with Triamcinolone Hexacetonide (TH) and Saline Solution (SS), in patients with knee osteoarthritis (OA). DESIGN: A randomized controlled trial, with blinded patients and assessor. SETTING: Outpatient rheumatology service. SUBJECTS: Patients with knee osteoarthritis grades II and III. INTERVENTIONS: Patients received IAI with PRP, 40 mg TH, or SS. METHODS: Patients were assessed at baseline and after 4, 8, 12 e 52 weeks with: visual analogue scale (VAS) for pain at rest and movement, WOMAC questionnaire, Timed to Up and Go test, 6-min walk test, percentage of improvement, goniometry, quality of life SF-36 questionnaire, Likert scale and Kelgreen & Lawrence (KL) radiographic scale (only at baseline and 52 weeks). RESULTS: 100 patients were studied, with a mean age of 67.13(6.56) years. The TH group was superior for: percentage of improvement (versus SS group from 4 to 52 weeks); WOMAC total and pain (versus PRP group at 4 weeks); and WOMAC stiffness (versus SS group at 12 weeks). The SS group was inferior for WOMAC function (from 8 to 52 weeks). The PRP group showed lowest radiographic progression [TH 17 (51.51%) to 24 (72.72%); SS 17 (51.51%) to 30 (90.90%); PRP 20 (58.82%) to 21 (61.76%)]. CONCLUSION: The Triamcinolone Hexacetonide group was superior for percentage of improvement and WOMAC, pain and stiffness. For the WOMAC function, the Platelet-Rich Plasma group and Triamcinolone Hexacetonide group were superior to the Saline group. The Platelet-Rich Plasma group showed the lowest radiographic progression at 52 weeks of follow-up.

Effect of the combination of photobiomodulation therapy and the intralesional administration of corticoid in the preoperative and postoperative periods of keloid surgery: A randomized, controlled, double-blind trial protocol study.

Keloid scars are characterized by the excessive proliferation of fibroblasts and an imbalance between the production and degradation of collagen, leading to its buildup in the dermis. There is no "gold standard" treatment for this condition, and the recurrence is frequent after surgical procedures removal. In vitro studies have demonstrated that photobiomodulation (PBM) using the blue wavelength reduces the proliferation speed and the number of fibroblasts as well as the expression of TGF-ß. There are no protocols studied and established for the treatment of keloids with blue LED. Therefore, the purpose of this study is to determine the effects of the combination of PBM with blue light and the intralesional administration of the corticoid triamcinolone hexacetonide on the quality of the remaining scar by Vancouver Scar Scale in the postoperative period of keloid surgery. A randomized, controlled, double-blind, clinical trial will be conducted involving two groups: 1) Sham (n = 29): intralesional administration of corticoid (IAC) and sham PBM in the preoperative and postoperative periods of keloid removal surgery; and 2) active PBM combined with IAC (n = 29) in the preoperative and postoperative periods of keloid removal surgery. Transcutaneous PBM will be performed on the keloid region in the preoperative period and on the remaining scar in the postoperative period using blue LED (470 nm, 400 mW, 4J per point on 10 linear points). The patients will answer two questionnaires: one for the assessment of quality of life (Qualifibro-UNIFESP) and one for the assessment of satisfaction with the scar (PSAQ). The team of five plastic surgeons will answer the Vancouver Scar Scale (VSS). All questionnaires will be administered one, three, six, and twelve months postoperatively. The keloids will be molded in silicone prior to the onset of treatment and prior to excision to assess pre-treatment and post-treatment size. The same will be performed for the remaining scar at one, three, six, and twelve months postoperatively. The removed keloid will be submitted to histopathological analysis for the determination of the quantity of fibroblasts, the organization and distribution of collagen (picrosirius staining), and the genic expression of TGF-ß (qPCR). All data will be submitted to statistical analysis. Trial registration: This study is registered in ClinicalTrials.gov (ID: NCT04824612).

The efficacy and safety of intra-articular injection of triamcinolone acetonide versus triamcinolone hexacetonide for treatment of juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. Intra-articular corticosteroids joint injection (IAJI), with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA), is an effective additional treatment for oligo and polyarticular JIA. Previous studies have shown the benefits of TH over TA; however, TA is still used in many pediatric rheumatology centers. Our unit has experience with both regimens, and therefore we aimed to compare the efficacy and safety of TA versus TH for JIA patients. METHODS: Chart review of JIA patients who were randomly (based on drug availability) treated with TA or TH IAJI during 2010-2019. Primary outcomes for efficacy were defined as full recovery from arthritis one month after IAJI and a relapse rate of arthritis 3 months after IAJI. Primary outcome for safety was defined as the occurrence of adverse events (AEs) during the follow up period after IAJI. RESULTS: Overall, 292 joints of 102 JIA patients were treated (138 TA/154 TH joints). Complete recovery after one month was documented in 107 (69.6%) of TA treated joints and 96 (69.5%) of TH treated joints (P = 0.232). However, rate of relapse after 3 months was significantly higher for TA treated joints (27 (20.1%) vs. 13 (8.8%), respectively, P < 0.01). No AEs were documented except minor scars at four joint injection sites. CONCLUSION: The recovery from arthritis was similar (~ 70%) with both regimens, however relapse rate was more than double in TA as compared to TH injected joints. These findings are important due to a contemporary shortage of TH in the US market.

The SPIKES protocol does not influence the tolerance or effectiveness of intra-articular corticosteroid injection in the knees of osteoarthritis patients: A prospective, controlled, randomized single-blinded trial.

BACKGROUND: Patient user embracement involves behaviours of including and listening to the patient, appreciating their complaints, and identifying their needs, whether individual or collective. The aim of this study was to evaluate the influence of a user embracement protocol (SPIKES protocol) for patients with knee osteoarthritis (OA) immediately before intra-articular injection (IAI) relative to procedure tolerance and its effectiveness in the immediate, short and medium terms. METHODS: This was a randomized controlled trial. Patients received IAIs with triamcinolone hexacetonide (40 mg) preceded or not by the SPIKES protocol. The outcomes measured were: visual analogue scale for pain at rest, pain on movement and joint swelling; morning stiffness; Western Ontario McMaster Universities Index Functional Questionnaire (WOMAC); pain catastrophizing scale; McGill pain questionnaire; SF-36 questionnaire on quality of life; Trace State Anxiety Inventory (IDATE); and a Timed Up and Go functional test. RESULTS: One hundred patients were randomized in the user embracement group (n = 50) or the control group (n = 50); 89% were women and 60% white, mean age was 67.1 (±7.3) years, and mean disease time was 6.3 (±6.2) years. No statistically significant differences were found between the groups for any variables at pre-procedure time, nor did the groups differ in their tolerance to the procedure or during the 12 weeks of follow up for any evaluated variables. CONCLUSIONS: No benefit was identified by applying a user embracement protocol to patients with knee OA prior to IAI with corticosteroid, neither to tolerance at the time of the procedure nor to its effectiveness in the immediate, short, and medium terms.

Response to treatment with intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligo articular juvenile idiopathic arthritis.

BACKGROUND: Oligo-articular juvenile idiopathic arthritis (Oligo JIA) is the most common subtype of juvenile idiopathic arthritis. Intra-articular corticosteroid (IAC) injection is a mainstay treatment of oligo JIA providing pain relief, improving mobility and preventing further joint destruction in the majority of patients. In 2015, production of triamcinolone hexacetonide (TH) an intra-articular corticosteroid was discontinued in the United States leading to use of triamcinolone acetonide (TA) as an alternative. In this study, we compared response to treatment in children with oligo JIA who underwent therapy with intra-articular TA and TH injection. METHODS: Our study is a retrospective chart review of children with oligo JIA who were treated with IAC injections with TH between January 2012 and June 2015 and TA between J uly 2015 and December 2018. The two groups were followed at John R. Oishei Children's Hospital of Buffalo and were evaluated for response to treatment, side effects and predictors of response including duration of disease before treatment, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Response to treatment was defined as at least 6 months follow up without evidence of active arthritis in injected joints. Patients were considered to be non-responders if they continued to show active arthritis during their first follow up after joint injection. The primary objective was to evaluate whether there was a significant difference in rate of response between TH and TA. RESULTS: Forty-nine patients, 38 female and 11 male with oligo JIA were included in the study. The average age was 6.7 years. A total of 111 joints were injected includin g 78 knees, 13 ankles, 9 wrists, 4 hips, 4 elbows, 2 TMJ and one subtalar joint. In the TA group, 49% (29/59) did not show response to injection compared to 27% (14/52) in the TH group. After 6 months, response rates were better for individuals injected with TH compared to TA (73% vs. 51%). In general, response to intra-articular TH was superior to TA with P = .016 using chi-square test of independence. This difference in outcome was not influenced by other variables such as duration of illness before treatment (P value 0.784) or elevated ESR and CRP. No difference in side effects between the two groups were noted. CONCLUSION: Our results in conjunction with prior published data suggests that TH intra-articular joint injection in oligo JIA is superior to TA, although future controlled trials are necessary for confirmation. An effective, long lasting treatment can have a great impact on the outcome of these children.

Intraarticular triamcinolone hexacetonide, stanozolol, Hylan G-F 20 and platelet concentrate in a naturally occurring canine osteoarthritis model.

Osteoarthritis (OA) is a disease transversal to all mammals, a source of chronic pain and disability, a huge burden to societies, with a significant toll in healthcare cost, while reducing productivity and quality of life. The dog is considered a useful model for the translational study of the disease, closely matching human OA, with the advantage of a faster disease progression while maintaining the same life stages. In a prospective, longitudinal, double-blinded, negative controlled study, one hundred (N = 100) hip joints were selected and randomly assigned to five groups: control group (CG, n = 20, receiving a saline injection), triamcinolone hexacetonide group (THG, n = 20), platelet concentrate group (PCG, n = 20), stanozolol group (SG, n = 20) and hylan G-F 20 group (HG). Evaluations were conducted on days 0 (T0, treatment day), 8, 15, 30, 60, 90, 120, 150 and 180 days post-treatment, consisting of weight distribution analysis and data from four Clinical Metrology Instruments (CMI). Kaplan-Meier estimators were generated and compared with the Breslow test. Cox proportional hazard regression analysis was used to investigate the influence of variables of interest on treatment survival. All results were analyzed with IBM SPSS Statistics version 20 and a significance level of p < 0.05 was set. Sample included joints of 100 pelvic limbs (of patients with a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. Joints were graded as mild (n = 70), moderate (n = 20) and severe (n = 10) OA. No differences were found between groups at T0. Kaplan-Meier analysis showed that all treatments produced longer periods with better results in the various evaluations compared to CG. Patients in HG and PCG took longer to return to baseline values and scores. A higher impact on pain interference was observed in THG, with a 95% improvement over CG. PCG and HG experienced 57-81% improvements in functional evaluation and impairments due to OA, and may be a better options for these cases. This study documented the efficacy of several approaches to relieve OA clinical signs. These approaches varied in intensity and duration. HG and PCG where the groups were more significant improvements were observed throughout the follow-up periods, with lower variation in results.

The intra-articular administration of triamcinolone hexacetonide in the treatment of osteoarthritis. Its effects in a naturally occurring canine osteoarthritis model.

OBJECTIVE: To evaluate the effect of an intra-articular (IA) administration of triamcinolone hexacetonide, compared with saline. PATIENTS AND METHODS: Forty (N = 40) hip joints were randomly assigned to a treatment group (THG, n = 20, receiving IA triamcinolone hexacetonide) and a control group (CG, n = 20, receiving IA saline). On treatment day (T0), and at 8, 15, 30, 90 and 180 days post-treatment, weight distribution, joint range of motion, thigh girth, digital thermography, radiographic signs, synovial fluid interleukin-1 and C-reactive protein levels were evaluated. Data from four Clinical Metrology Instruments was also gathered. Results were compared Repeated Measures ANOVA, with a Huynh-Feldt correction, Paired Samples T-Test or Wilcoxon Signed Ranks Test. A Kaplan-Meier test was performed to compare both groups, with p<0.05. RESULTS: Joints were graded as mild (65%), moderate (20%) and severe (15%). Patients of both sexes, with a mean age of 6.5±2.4 years and bodyweight of 26.7±5.2kg, were included. No differences were found between groups at T0. Comparing THG to CG, weight distribution showed significant improvements in THG from 8 (p = 0.05) up to 90 days (p = 0.01). THG showed lower values during thermographic evaluation in the Lt view (p<0.01). Pain and function scores also improved from 30 to 180 days. Increasing body weight, age, and presence of caudolateral curvilinear osteophyte corresponded to worse response to treatment. Results of the Kaplan Meier test showed significant differences between groups, with THG performing better considering several evaluations and scores. CONCLUSION: THG recorded significant improvements in weight-bearing and in with the considered CMIs, particularly pain scores. Lower thermographic values were registered in THG up to the last evaluation day. Age, sex, and radiographic findings did significantly influenced response to treatment.

Efficacy and safety of intraarticular corticosteroid injections in adolescents with juvenile idiopathic arthritis in the temporomandibular joint: a Norwegian 2-year prospective multicenter pilot study.

BACKGROUND: Intraarticular corticosteroids (IACs) have been used to treat temporomandibular joint (TMJ) arthritis. However, prospective clinical studies with magnetic resonance imaging (MRI) scoring are lacking. The aim of this study was to examine efficacy and safety of a single IAC in the TMJ in adolescents with juvenile idiopathic arthritis (JIA) in a clinical setting. METHODS: In this Norwegian prospective multicenter pilot study 15 patients with JIA (mostly persistent oligoarthritis or RF negative polyarthritis categories) and a clinically and MRI-verified diagnosis of TMJ arthritis were treated with IACs and followed for 2 years. Demographics, systemic medication, general disease activity and outcome measures were recorded including a pain-index score and maximal incisal opening (MIO). Inflammation and bone damage scores were assessed, using two recently published MRI scoring systems with masked radiological evaluation. RESULTS: Among the 15 patients, 13 received a single IAC (5 bilateral), and 2 repeated IACs once unilaterally. Thus, the total number of IACs was 22. Median age was 15 years and the majority had an age not thought of as critical regarding mandibular growth retardation due to steroid injection. During the 2-year observation period systemic medication with disease modifying antirheumatic drugs (DMARDs) including biologics was initiated or adjusted in 10/15 (67%) patients. At the 2-months study visit after injection we observed a minimal improvement in MIO from median 44 (1st, 3rd quartiles; 36, 48) mm to 45 (43, 47) mm, p = 0.045 and decreased MRI mean additive inflammatory score from 4.4 ± 1.8 standard deviations (SD) to 3.4 ± 2.0, p = 0.040. From baseline to the 2-months follow-up pain improved in 6/11 patients but pain scores were not significantly improved. MRI-assessed damage increased in two patients with repeated IACs, and decreased in 3 patients but most of the patients were stable over the 2-year follow-up. Intra-rater repeatability of the MRI scoring system domains varied from poor to excellent. CONCLUSIONS: In this pilot study of predominately single IACs to the TMJ in combination with systemic treatment we observed improvement in MRI-assessed inflammation, mostly stable condylar bone conditions and minimal clinical improvement in adolescents with JIA and TMJ arthritis. No severe side effects were seen.

Intralesional injection of triamcinolone hexacetonide as an alternative treatment for central giant cell lesions: a prospective study.

The aim of this prospective study was to report on the response to treatment of central giant cell lesions (CGCL) with intralesional corticosteroid injections. Consecutive cases of CGCL were treated with a biweekly intralesional injection of 20mg/ml triamcinolone hexacetonide diluted in an anaesthetic solution of 2% lidocaine/epinephrine 1:200 000 at the proportion 1:1. All patients were monitored using cone beam computed tomography. Eleven patients were treated; their ages ranged from 15-34 (mean 22 years); and eight lesions were in the mandible, and three in the maxilla. Three cases were diagnosed as non-aggressive, and eight as aggressive. Six cases presented good results (four aggressive and two non-aggressive); three cases presented a moderate response (two aggressive and one non-aggressive); and two had a poor response to treatment (both aggressive). In four cases with a good response, osteoplasty was done. In all cases with a moderate response, the remaining lesion was curetted. Cases with a poor response were submitted to either curettage or denosumab injections. Corticotherapy, as main or neoadjuvant therapy, may be an option for treatment of CGCL.

Image guided sacroiliac joint corticosteroid injections in children: an 18-year single-center retrospective study.

BACKGROUND: Sacroiliitis is commonly seen in enthesitis-related arthritis (ERA), a subtype of juvenile idiopathic arthritis (JIA). Sacroiliitis is characterized by the inflammation of the sacroiliac (SI) joints (+/- adjacent tissues). The treatment options include systemic therapy with or without corticosteroid SI joint injections. Image guided SI joint injections are frequently requested in pediatric patients with sacroiliitis. The purpose of this study was to evaluate the feasibility and efficacy of SI joint injections in children with sacroiliitis. METHODS: A retrospective study of patients referred to Interventional Radiology (IR) for SI joint corticosteroid injections (2000-2018). Clinical information was collected from Electronic Patient Charts and procedural details from PACS. Efficacy was determined clinically, by MRI, or both when available. RESULTS: 50 patients (13.8 years; M:F = 35:15) underwent image-guided SI joint corticosteroid injections. Most common indications were JIA (84%) and inflammatory bowel disease (14%). 80% had bilateral injections. 80% were performed under general anesthesia and 20% under sedation. The corticosteroid of choice was triamcinolone hexacetonide in 98% of patients. Needle guidance and confirmation was performed using CT and fluoroscopy (54%), Cone Beam CT (CBCT, 46%), with initial ultrasound assistance in 34%. All procedures were technically successful without any complications. 32/50 patients had long-term follow-up (2 years); 21/32 (66%) had clinical improvement within 3-months. Of 15 patients who had both pre- and post-procedure MRIs, 93% showed short-term improvement. At 2 years, 6% of patients were in remission, 44% continued the same treatment and 47% escalated treatment. CONCLUSION: Image-guided SI joint injections are safe and technically feasible in children. Imaging modalities for guidance have evolved, with CBCT being the current first choice. Most patients showed short-term clinical and imaging improvement, requiring long-term maintenance or escalation of medical treatment.

Time Effect of Intra-articular Injection With Triamcinolone Hexacetonide and Its Correlations: A Case-Control Prospective 12-Month Study.

OBJECTIVE: The aim of the study was to assess the time effect of intra-articular injection with triamcinolone hexacetonide in rheumatic patients. DESIGN: A prospective case-control study with patients submitted to one intra-articular injection with triamcinolone hexacetonide. Patients were followed monthly (12 mos) for pain and swelling. RESULTS: Two hundred sixty-two joints were assessed in 158 patients with mean ± SD age of 60 ± 13.7 yrs. Remission was observed at 3, 6, and 12 mos in 142 (54.19%), 111 (42.36%), and 105 (40.07%) joints, respectively. The mean ± SD time effect were 8 ± 4.0 mos; 8.4 ± 3.9 for rheumatoid arthritis patients and 6.9 ± 4.0 for osteoarthritis patients (P = 0.012) and 10.4 ± 2.7 mos for small, 7.7 ± 4.1 for medium, and 6.8 ± 4.0 for large joints. The joints were divided into two groups: long-term group (time effect of intra-articular injection longer than 6 mos) and short-term group. The following are the variables associated (P < 0.05) with long-term group: rheumatoid arthritis, small and medium-sized joints, female sex, lower pain and swelling visual analog scale scores, and use of leflunomide. The following are the variables associated with short-term group: receiving only one intra-articular injection, hypertension, diabetes mellitus, and biological therapy. CONCLUSIONS: The mean ± SD time effect of intra-articular injection with triamcinolone hexacetonide was 8.0 ± 4.0 mos. The associated predictors were rheumatoid arthritis, small and medium joints, lower pain/swelling visual analog scale scores, and use of leflunomide.

Retrospective review of immobilization vs. immediate resumption of activity in patients with Oligoarticular juvenile idiopathic arthritis following knee injections.

BACKGROUND: Intraarticular corticosteroid injection (IACI) is one of the most common treatments in oligoarticular Juvenile Idiopathic Arthritis (JIA). Activity recommendations following injection vary, as there are no published studies on splinting JIA patients post-IACI (splinting is a form of rest). Texas Scottish Rite Hospital for Children (TSRH) splints patients post-IACI for 24 h while The Children's Hospital of Philadelphia (CHOP) does not. The aim of this study was to compare the number of cases of recurrent arthritis following IACI between these two post-injection practices. METHODS: Data were retrospectively collected at CHOP and TSRH. Patients diagnosed with oligoarticular JIA according to International League of Associations for Rheumatology (ILAR) criteria (2nd revision, 2001) between 2008 and 2010 were included. Bivariate analysis (Wilcoxon rank-sum tests, chi-squared tests) was run to assess differences in outcomes by site. Inverse probability of treatment weighted Cox regression was employed to adjust for site differences. RESULTS: The population at TSRH was younger than at CHOP (p < 0.05) and had more whites (p = 0.03). Disease duration was significantly longer at TSRH than at CHOP (0.40 vs. 0.74 years, p = 0.014). More children were on biologics at the time of injection at CHOP (p < 0.05). The baseline physician global (p < 0.001) was higher at CHOP, as was the joint disease severity (p < 0.001). CHOP had fewer reoccurrences of knee arthritis compared to TSRH: 26% vs 38% (p = 0.14). CONCLUSIONS: The baseline populations were different in that the TSRH group had more whites and Hispanics, were younger and, perhaps, had less severe disease than CHOP. Patients treated with post-injection splinting had a trend toward more arthritis reoccurrence (38% vs. 26%, p = 0.14). Splinting is not clearly beneficial post-injection. TRIAL REGISTRATION: This is an observational study, so it is not applicable.

The evaluation of the effectiveness of intra-articular steroid, tenoxicam, and combined steroid-tenoxicam injections in the treatment of patients with knee osteoarthritis.

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.

Elimination profile of triamcinolone hexacetonide and its metabolites in human urine and plasma after a single intra-articular administration.

Triamcinolone hexacetonide (THA) is a synthetic glucocorticoid (GC) used by intra-articular (IA) administration. GCs are prohibited in sports competitions by systemic routes, and they are allowed by other routes considered of local action (IA administration, among others). The aim of the present work was to study the metabolic profile of THA in urine and plasma following IA administration. Eight patients (4 males and 4 females) with knee osteoarthritis received an IA dose of THA (40 mg) in the knee joint. Spot urine and plasma samples were collected before injection and at different time periods up to day 23 and 10 post-administration, respectively. The samples were analysed by liquid chromatography-tandem mass spectrometry. Neither THA nor specific THA metabolites were detected in urine. Triamcinolone acetonide (TA) and 6ß-hydroxy-triamcinolone acetonide were the main urinary metabolites. Maximum concentrations wereobtained between 24 and 48 h after administration. Using the reporting level of 30 ng/mL to distinguish allowed from forbidden administrations of GCs, a large number of false adverse analytical findings would be reported up to day 4. On the other hand, TA was detected in all plasma samples collected up to day 10 after administration. THA was also detected in plasma but at lower concentrations. The detection of plasma THA would be an unequivocal proof to demonstrate IA use of THA. A reversible decrease was observed in plasma concentrations of cortisol in some of the patients, indicating a systemic effect of the drug.

Dosing of intra-articular triamcinolone hexacetonide for knee synovitis in chronic polyarthritis: a randomized controlled study.

Objective: Intra-articular glucocorticoid (IAGC) injection treatment is an easy and effective way to treat the signs and symptoms of arthritis, but there is limited knowledge on the adequate dosing for different joints. The aim of this study was to compare the outcome between two common doses of intra-articular triamcinolone hexacetonide (THA) for knee synovitis using the relapse rate during 6 months. Methods: A total of 159 adult patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) and active knee synovitis were randomized to IAGC injection with 20 mg or 40 mg THA. Participants were blinded to the treatment dose. The primary endpoint was relapse of arthritis. When symptoms from the treated joint recurred and signs of arthritis could be confirmed on a subsequent clinical examination, a relapse was recorded and the duration of response survival was calculated. At the end of the observation period, patients without relapse were telephoned to verify the persistence of the good treatment response. Results: The proportion of relapse after 6 months was equal in the 20 mg and 40 mg THA treatment arms (30% vs 32%, respectively, p = 0.822), and no significant differences were found in the subgroups with RA and PsA patients. Conclusion: As no difference in outcome was found between the compared doses, the lower 20 mg THA dose should be preferred in IAGC treatment for knee synovitis in chronic polyarthritis. This may also reduce pharmaceutical costs and metabolic side effects. EudraCT number: 2014-000993-20, Clinical Trials.gov identifier: NCT02437461.

Comparison between intra-articular Botulinum toxin type A, corticosteroid, and saline in knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of intra-articular injection (IAI) with Botulinum toxin type A (BTA), triamcinolone hexacetonide (TH), and saline in primary knee osteoarthritis. DESIGN: A randomized controlled trial, with blinded patients and assessor. SETTING: Outpatient rheumatology service. SUBJECTS: Patients with knee osteoarthritis grades II and III. INTERVENTIONS: Patients received IAI with 100 IU BTA, 40 mg TH, or isotonic saline solution (SS) 0.9%. MAIN MEASURES: Patients were assessed at baseline and at 4, 8, and 12 weeks with the following instruments: visual analog scale for pain during movement (VASm; primary outcome) and visual analog scale for pain at rest (VASr), Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, 6-minute walk test, Timed Up and Go test, Short Form (SF)-36 questionnaire, range of motion of knee, and ultrasound (US) measurement of synovial hypertrophy. RESULTS: In total, 105 patients were randomized, with 35 in each group; 96 were female (91.4%) and 9 were male (8.6%), with a mean age of 64.2 years (±6.9). At 12 weeks, the TH group showed better results only for VASm. At four weeks, the TH group showed better results than the BTA and SS groups for VASm (-68.9% (37.8) vs. -35.3% (40.3) vs. -35.9% (51.4)), WOMAC pain (-56.0% (30.7) vs. -30.8% (34.3) vs. -30.0% (39.9)), WOMAC stiffness (-53.4% (38.4) vs. -17.2% (59.3) vs. -17.3% (78.1)), WOMAC function (-48.2% (34.6) vs. 30.8% (33.6) vs. -13.6% (64.9)), WOMAC total score (-51.2% (31.0) vs. -30.9% (30.0) vs. -18.8% (54.8)), and US measurement of synovial hypertrophy (-11.6% (44.9) vs. -1.5% (47.9) vs. +28.6% (81.3)). CONCLUSION: IAI with TH had a higher effectiveness than that with TBA or SS in the short-term assessment (four weeks) for pain in movement, WOMAC, and US measurement of synovial hypertrophy.

Simultaneous determination of triamcinolone hexacetonide and triamcinolone acetonide in rabbit plasma using a highly sensitive and selective UPLC-MS/MS method.

An ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was successfully developed and qualified for the simultaneous determination of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TAA, the active metabolite of TAH) in rabbit plasma. To prevent the hydrolysis of TAH to TAA ex vivo during sample collection and processing, we evaluated the effectiveness of several esterase inhibitors to stabilize TAH in plasma. Phenylmethanesulfonyl fluoride (PMSF) at 2.0 mM was chosen to stabilize TAH in rabbit plasma. The developed method is highly sensitive with a lower limit of quantitation of 10.0 pg/mL for both TAA and TAH using a 300 µL plasma aliquot. The method demonstrated good linearity, accuracy, precision, sensitivity, selectivity, recovery, matrix effects, dilution integrity, carryover, and stability. Linearity was obtained over the range of 10-2500 pg/mL. Both intra- and inter-run coefficients of variation were less than 9.1% and accuracies across the assay range were all within 100 ±â€¯8.4%. The run time is under 5 minutes. The method was successfully implemented to support a rabbit pharmacokinetic study of TAH and TAA following a single intra-articular administration of TAH (Aristospan®).

Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. DESIGN: This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. RESULTS: A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. CONCLUSIONS: Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.