Treatment Of Symptomatic Knee Osteoarthritis Research Articles

Efficacy evaluation of highly purified intra-articular hyaluronic acid (Sinovial ®) vs hylan G-F20 (Synvisc ®) in the treatment of symptomatic knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non-inferiority study

Knee osteoarthritis is a major cause of disability and pain. This phase III, double-blind (patient and observer blinded,) multicenter, randomized, non-inferiority study was conducted to demonstrate the non-inferiority of the highly purified intra-articular injection of hyaluronic acid (Sinovial(®)) in comparison to Hylan G-F20 (Synvisc(®)) in the treatment of knee osteoarthritis. A total of 381 patients were randomly assigned to receive either the test drug, 16 mg/2 ml (0.8%) highly purified ia hyaluronic acid of biofermentative origin (Sinovial(®)), or the comparative drug, 16 mg/2 ml of 0.8% hylan G-F20 (Synvisc(®)). The duration of the treatment was 2 weeks (three injections at 1-week interval), followed by an observation period of 6 months. The primary efficacy variable was the improvement in mean Western Ontario and McMaster Universities (WOMAC) pain subscore from baseline to the final visit (week 26), compared between the two treatment groups. The acceptable margin for non-inferiority was chosen to be 8 mm. At week 26, WOMAC pain subscores decreased by a mean of 32.5 for both Sinovial(®) and Synvisc(®). These results met prespecified criteria for non-inferiority for both the Intent-to-Treat and Per-Protocol populations. There were no statistically significant differences between groups at 26 weeks, although Sinovial(®)-treated patients tended to have a slightly better outcome for select variables, as they did at earlier time-points, some of which reached statistical significance. Both hyaluronic acid preparations were well-tolerated, with no statistically significant differences in tolerability profile between groups. Sinovial(®) and Synvisc(®) treatments were found to be equivalent, both in terms of efficacy and safety. NCT00556608 (ClinicalTrials.gov Identifier).

Accurate intra-articular knee joint injection in the obese? ’Fat Chance!’—A clinical lesson and recommendations for secondary referral

Corticosteroid joint injections are perceived as being an effective treatment for symptomatic knee osteoarthritis, with a very low risk of complications. While the procedure is often performed in secondary care by orthopaedic surgeons and rheumatologists (and trainees in either specialty), the role of general practitioners (GPs) in chronic disease management has long existed with joint injections also frequently performed in primary care. The perception that serious complications from corticosteroid knee joint injections are rare and that their benefits in treating symptomatic knee osteoarthritis significantly outweigh the risks has not been well addressed. We present a case of a 71-year-old obese female who presented to her general practitioner (GP) with worsening left knee pain and radiographic changes consistent with osteoarthritis. She was administered a corticosteroid joint injection, which gave minimal relief, and over the next few days resulted in worsening severe pain, erythema and swelling. She returned to the GP who commenced oral antibiotics and referred her to casualty. A large knee abscess was diagnosed and intravenous antibiotics were commenced. The patient was admitted under the orthopaedic surgeons with her treatment consisting of multiple surgical procedures over a prolonged duration. Although lengthy, her postoperative recovery was unremarkable. Based on this case report and our review of the literature, we highlight the potential complications associated with corticosteroid knee joint injections and suggest certain patients for whom we would recommend secondary referral before any intervention in primary care.

The effect of mud pack therapy on serum YKL-40 and hsCRP levels in patients with knee osteoarthritis

The aim of this study was to evaluate the efficacy of treatment with mud pack in knee osteoarthritis (OA) and to determine whether mud pack effects serum levels of YKL-40 and high-sensitivity C-reactive protein (hsCRP) which are reported to be biological markers for articular damage or inflammation in patients with OA. Forty-four patients with the diagnosis of knee OA assigned into two groups were treated with local natural mineral-rich mud pack or hot pack. Treatments were applied for 6 days a week for 2 weeks as a total of 12 sessions. Patients were assessed at baseline, post-treatment, and 3 months after the treatment. VAS, range of motion, 15-m walking time, WOMAC index, Nottingham Health Profile, serum YKL-40, and hsCRP levels were the outcome measures. Pain intensity and joint stiffness decreased in both groups at all follow-ups. Physical activity status was found to persist for 3 months after treatment only in mud pack group. Serum mean YKL-40 and hsCRP levels of the patients were higher compared to healthy control group. Serum YKL-40 level increased significantly only in hot pack group 3 months after the treatment (P < 0.017). No significant change was observed in hsCRP levels in both groups during the whole follow-up periods (P > 0.05). Mud pack and hot pack therapy were both demonstrated to be effective in symptomatic treatment of knee OA until the end of the 2-week treatment period, whereas only mud pack therapy was shown to be effective in functional status over time. In the hot pack group, increased serum YKL-40 level 3 months after the treatment might indicate persistence of cartilage degradation. Maintenance of YKL-40 level in mud pack therapy seems to slow down the progression of knee OA.

Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.

Inflammatory Characteristics on Ultrasound Predict Poorer Longterm Response to Intraarticular Corticosteroid Injections in Knee Osteoarthritis

To assess whether inflammation on ultrasound is predictive of clinical response to intraarticular (IA) corticosteroid injections in patients with knee osteoarthritis (OA). Patients with symptomatic knee OA were randomized to receive either an IA injection of 40 mg triamcinolone acetonide in the treatment group or 1 cc 0.9% saline in the placebo group. Clinical response was assessed by changes in baseline Western Ontario and McMaster Universities (WOMAC) index scores and physician global assessment at 4 and 12 weeks. Ultrasounds were performed at each visit. Patients and assessors were blinded to treatment status. Seventy-nine patients were enrolled into the study. Four-week data were available for 67 patients in the primary analysis comparing change in WOMAC pain score from baseline to 4 weeks. There was almost no change in the WOMAC pain subscale score from baseline to 4 weeks in the control group, but there was a significant improvement in WOMAC pain subscale score from 10.8 (SD +/- 3.2) at baseline to 8.75 (SD +/- 4.0) at 4 weeks in the treatment group (adjusted p = 0.001). Of the 34 patients in the treatment group; 16 (47%) had inflammatory disease and 18 (53%) had noninflammatory disease as determined by ultrasound. There was no difference in the change in WOMAC pain score between the inflammatory and noninflammatory patients in the treatment group at 4 weeks. There was a statistically significant greater improvement in pain subscale scores among noninflammatory patients than among inflammatory patients at 12 weeks. Intraarticular corticosteroid injections are an effective short-term treatment for symptomatic knee OA compared to placebo. Patients with noninflammatory characteristics on ultrasound had a more prolonged benefit from IA corticosteroids compared to inflammatory patients.

Long-term experience with hylan GF-20 in the treatment of knee osteoarthritis

Background: Osteoarthritis is the most frequent musculoskeletal disease and a major cause of disability in the elderly. Knee osteoarthritis is the first cause of consultations for osteoarthritis-related symptoms. Its current management requires the combination of pharmaceutical and non-pharmacological strategies, including intra-articular injections of hyaluronic acid that are aimed at decreasing pain and improving joint function by restoring joint homeostasis (viscosupplementation). Hylan GF-20 is a cross-linked hyaluronic acid derivative, FDA approved as a medical device since 1997 for the treatment of patients with symptomatic knee osteoarthritis. Objectives: This review aims to summarise recently published evidence and offer practical suggestions to clinical colleagues who are considering including viscosupplementation in their practices. Methods: The authors reviewed extensively the published papers on the topic, but selected only those that appeared to be the most relevant, on the mechanisms of action, efficacy and safety of the treatment, clinical predictors of response, ideal dosing regimen and differences between commercial preparations. They also give their own clinical experience with hylan GF-20 as a symptomatic treatment of knee osteoarthritis. Conclusion: Data of the literature clearly demonstrate that hylan GF-20 is a safe and effective treatment for decreasing pain and improving function in patients suffering from knee osteoarthritis. Its long-term (10 years) use allows knowing with accuracy the main indications, contraindications, side effects and prognostic factors of response, which are all extensively discussed throughout this review.

Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study

Viscosupplementation by repeated intra-articular injections of hyaluronic acid (HA) is used widely in the treatment of symptomatic knee osteoarthritis (OA). The number of injections required can limit the availability of treatment and affect patient compliance. The aim of this study was to assess different dosing regimens of hylan G-F 20, a high molecular-weight cross-linked derivative of HA, in the treatment of pain due to knee OA. Pilot, prospective, multi-centre, open-label, randomised trial in 100 patients with unilateral, symptomatic, tibio-femoral OA (Kellgren-Lawrence grade II or III), aged > or =40 years. Patients were randomised to receive varying dosing regimens of hylan G-F 20 (1 x 6 mL, 1 x 4 mL, 2 x 4 mL 2 weeks apart, 3 x 4 mL 1 week apart, or 3 x 2 mL 1 week apart). Adverse events (AE's) were monitored throughout the study. The primary efficacy endpoint was the change from baseline in the patient-rated knee OA pain assessment (100 mm visual analogue scale (VAS)) at 24 weeks. The secondary efficacy criteria included the WOMAC index, patient and physician global assessments using a 100 mm VAS, and knee OA pain assessment at all other visits. Concomitant use of permitted rescue medications (paracetamol) was also assessed. The treatment was well tolerated overall. Patients in the 3 x 4 mL group reported the highest percentage of device-related local AE's (30%) while patients in the 1 x 6 mL and 3 x 2 mL groups reported only 10%. There were no serious device-related AEs. There was a statistically significant improvement from baseline at week 24 in all efficacy endpoints for all treatment regimens. The 1 x 6 and 3 x 4 and 3 x 2 mL treatment groups showed the greatest mean improvements (-34.9, -32.6 and -36.7 mm respectively) in the patient-rated knee OA pain assessment VAS. This study suggests that a single 6 mL injection of hylan G-F 20 may be as efficacious, and as well tolerated, as 3 x 2 mL one week apart. A double-blind, controlled trial is needed to confirm these data.

Viscosupplementation in Lumbar Facet Joint Arthropathy

Degeneration of the spine is a prevalent problem that generally advances with age, although its occurrence is not restricted to the elderly. Chronic low back pain is a common problem with several treatments, but rigorous evaluation of many interventions is still lacking. One of the most common methods of treating lumbar facet arthropathy is intra-articular injection of local anesthetic and steroid. However, in large joints, such as the knee, viscosupplementation has been shown to compare favorably to steroid in terms of symptom relief and duration of benefit. It is suggested that viscosupplementation may supersede steroid in treatment of symptomatic knee osteoarthritis. Hyaluronic acid (HA) therapy is still in its infancy in joints outside the knee, although some preliminary results are promising. This was a pilot study to test the potential effectiveness of HA injection therapy in the treatment of lumbar facet joint arthritis. Thirteen patients with symptomatic lumbar facet joint arthritis who met the inclusion criteria were prospectively recruited. Pretreatment evaluation of patients was by questionnaire, including the Visual Analog Score and Oswestry Disability Questionnaire. A single injection of HA into affected facet joints was then performed, with correct placement confirmed on fluoroscopy. The patients were similarly evaluated 6 weeks after treatment. Eighteen facets in 13 patients were injected with HA. At 6-week follow up, there was no significant improvement in pain when measured on the Visual Analog Score. There was also no significant improvement in the Oswestry Disability Questionnaire. Preliminary results from this pilot study do not demonstrate any benefit of viscosupplementation in the management of symptomatic lumbar facet arthropathy.

Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial

Incubation of blood with CrSO(4)-coated glass beads stimulates the synthesis of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, and IL-13. As IL-1beta is thought to play a key role in the development of osteoarthritis (OA), this product, also known as Orthokin, might be a viable treatment for symptomatic knee OA. The aim of the current study was to evaluate the efficacy of Orthokin for treatment of symptomatic knee OA in a randomized, multicentre, double-blind, placebo-controlled trial. One hundred and sixty-seven patients received six intra-articular injections either with Orthokin or physiological saline. The primary efficacy objective consisted of 30% superiority on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3, 6, 9, and 12 months post-treatment. Additionally, the patients completed the visual analogue scale for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Clinical Rating System. Orthokin and placebo treatment resulted in similar improvements on the WOMAC (16.8% vs 16.5%, respectively; n.s.). Orthokin resulted in significantly more improvement for KOOS symptom (P = 0.002) and KOOS sport (P = 0.042) parameters as compared to placebo treatment. For most other outcome parameters, Orthokin-treated patients consistently showed higher improvement compared to placebo-treated patients, although none of these differences were statistically significant. Two serious adverse events were observed in the Orthokin group: one patient with repeated severe inflammatory reactions of the knee joint within hours after the injection and one patient with septic arthritis which was attributed to the injection procedure rather than the product. The statistically significant improvement of KOOS symptom and sport parameters together with the consistently higher, though non-statistically significant, improvement of most other parameters demonstrates that Orthokin clearly induces a biological response different from placebo treatment and warrant future investigations into the possible chondroprotective effect of Orthokin. However, in the current study the primary efficacy objective was not met and, therefore, the use of Orthokin currently cannot yet be recommended for the treatment of OA.

Short-term treatment with topical diclofenac epolamine plaster in patients with symptomatic knee osteoarthritis: pooled analysis of two randomised clinical studies

ABSTRACTBackground: Data from two randomised, double-blind, placebo-controlled studies were considered in order to investigate the efficacy and safety of a bio-adhesive plaster for topical administration containing diclofenac epolamine (DHEP) in patients with symptomatic knee osteoarthritis (OA).Methods: Patients with radiologically confirmed symptomatic knee OA were included. The 14‐day treatment consisted of two daily applications of either DHEP or placebo plaster. The algofunctional Lequesne index and pain intensity, measured by means of the Huskisson's visual analogue scale (VAS), were considered as main efficacy parameters. The main analysis of the pooled data was by intention-to-treat.Results: Of the 258 patients included, 235 completed the study. At the end of the study, the mean decrease in the Lequesne index was 35% in the DHEP group and 15% in the placebo group ( p < 0.0001). The mean decrease in pain intensity was 59.5% in the DHEP group and 29.9% in the placebo group. No interaction resulted between treatment and study effects ( p ≥ 0.2 whatever the test). The non-parametric Hodges–Lehmann estimator of the treatment effect resulted in a reduction of 21.9% for the Lequesne index and of 30.0% in pain intensity.The number needed to treat (NNT) for at least a 50% reduction of pain was 3.0 and the effect size for pain was 0.75.Conclusions: Topical application of DHEP plaster was shown to be an efficacious and safe short-term treatment for symptomatic knee OA, reducing pain and increasing physical function and may be similar in efficacy to oral non-steroidal anti-inflammatory drugs (as indicated by relative benefit data and NNT value).

Overall tolerability and analgesic activity of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

ABSTRACTObjective: Viscosupplementation with intra-articular hyaluronic acid (HA) is an alternative to the treatment of symptomatic knee osteoarthritis (OA) with pain relieving drugs. Sinovial, is a sterile, non-pyrogenic 0.8% solution of highly purified sodium hyaluronate for intra-articular application. The aim of the present study was to investigate the safety and tolerability profile of this preparation in patients with symptomatic knee OA over 24 weeks.* Sinovial is a registered trade name of IBSA Institut Biochimique SA, Lugano, SwitzerlandResearch design and methods: This was a single group, open-label study, including outpatients of both sexes, aged between 18 and 85 years, with symptomatic knee OA. All patients underwent weekly intra-articular injections of HA for 5 consecutive weeks and were followed-up for 19 additional weeks. The safety and tolerability profile (primary endpoint) was assessed by adverse event (AE) reporting. The secondary endpoint was efficacy evaluated by changes in the Western Ontario and McMaster Universities (WOMAC) score vs. baseline. Patient and physician satisfaction were also recorded.Results: Intra-articular HA was generally well tolerated. The most frequent AE was pain at the injection site (5.8% of the injections); no serious treatment-related AE was reported. The WOMAC score was significantly reduced within the first 2 weeks of treatment (from 4.02 ± 1.90 to 3.55 ± 2.04, p = 0.0011), further decreased by the end of the injection series (week 6: 2.59 ± 1.90; p < 0.0001) and maintained during the follow-up (week 24: 2.44 ± 1.88; p < 0.0001). The WOMAC subscores were also significantly reduced from week 4 for ‘pain’ and from week 6 for ‘stiffness’ and ‘physical function’.Conclusions: In the present study, intra-articular HA was well tolerated and safe in patients with symptomatic knee OA. Based on the sustained improvements in WOMAC score and subscores, a carry-over effect lasting for at least 19 weeks after the last injection may be proposed. These results further confirm the evidence of efficacy and safety of intra-articular HA in the management of knee OA.

The Cost-Effectiveness of Acetaminophen, NSAIDs, and Selective COX-2 Inhibitors in the Treatment of Symptomatic Knee Osteoarthritis

Objective The objective of this study was to conduct an economic evaluation of rofecoxib and celecoxib compared with high-dose acetaminophen or ibuprofen with and without misoprostol for patients with symptomatic knee osteoarthritis (OA). Methods A decision analysis model was designed over 6 months using two measures of effectiveness: 1) number of upper gastrointestinal (GI) adverse events averted; and 2) number of patients who achieved perceptible pain relief. Separate analyses were conducted for all patients and for those who did not respond to acetaminophen. Outcome probabilities were obtained from a comprehensive review of randomized controlled trials and observational studies. Costs were derived from actual resource utilization of OA patients. Results In terms of averting GI events, acetaminophen dominates the other options for an average risk patient population. For patients who did not respond to acetaminophen, rofecoxib had the lowest incremental cost-effectiveness ratio (ICER) per GI event avoided ($32,000) relative to ibuprofen. In terms of pain control, ibuprofen had an ICER of $610.77 per additional patient achieving minimal perceptible clinical improvement (MPCI) relative to acetaminophen, while rofecoxib had an ICER of $12,000 relative to ibuprofen. For patients who did not respond to acetaminophen and who are at high risk of developing an adverse GI event, rofecoxib dominates ibuprofen as the preferred alternative for both measures of effectiveness. One-way, two-way, and probabilistic sensitivity analyses established that these results were generally robust. Conclusions Our results suggest that for average-risk knee OA patients, acetaminophen dominates the other therapies in terms of cost per GI event averted. In terms of pain relief, cost-effectiveness acceptability curves indicate that if one values pain relief below $275 per patient achieving MPCI, acetaminophen is the therapy most likely to be optimal; between $275 and $14,150, ibuprofen is most likely to be optimal; and above $14,150, rofecoxib is most likely to be optimal.

Comparison of Dexketoprofen Trometamol and Ketoprofen in the Treatment of Osteoarthritis of the Knee.

Dexketoprofen, the active enantiomer of the racemic compound ketoprofen, is a new nonsteroidal antiinflammatory drug (NSAID) of the arylpropionate family. The efficacy and safety of dexketoprofen trometamol were compared with the equivalent enantiomeric dose of ketoprofen in a multicenter, randomized, double-blind 3-week trial of adult outpatients with pain due to osteoarthritis of the knee. After a washout period of 7-15 days, patients were randomly assigned to receive either dexketoprofen trometamol 25 mg tid (N = 89) or ketoprofen 50 mg tid (N = 94). Of the 183 patients enrolled, two were lost to follow-up. At the end of treatment (3 weeks), the main efficacy outcome measures were significantly better in the dexketoprofen trometamol group than in the ketoprofen group. In addition, overall physician assessment indicated that 75% of the dexketoprofen group had improved compared with 50% of the ketoprofen patients. There were fewer adverse events in the dexketoprofen treatment group, but the difference did not reach statistical significance. These results demonstrate that dexketoprofen trometamol 25 mg tid is more effective than ketoprofen 50 mg tid in short-term symptomatic treatment of knee osteoarthritis and suggest that the tolerability of dexketoprofen trometamol is more favorable than ketoprofen. Therefore, the substitution of dexketoprofen for racemic ketoprofen may be advantageous in clinical practice.

Efficacy of traditional Chinese acupuncture in the treatment of symptomatic knee osteoarthritis: a pilot study

Efficacy of traditional Chinese acupuncture in the treatment of symptomatic knee osteoarthritis: a pilot study