OBJECTIVES: The aim of the present study was to compare the clinical results and the quality of life in patients with symptomatic knee osteoarthritis randomised to either a new HA (HYADD 4) or corticosteroid (CS). A separate rationale was to evaluate the safety profile of HYADD 4.
METHODS: All the patients presenting for unilateral symptomatic primary knee osteoarthritis were prospectively randomly assigned to receive 2 injections of either HYADD 4 or CS, and were evaluated before the injections and at 6, 12, 26 and 52 weeks. Primary end point was WOMAC score at 26 weeks; secondary end points were WOMAC score, VAS for pain, and SF-36 score at any time point.
RESULTS: There were 53 females and 22 males in the HYADD 4 group (mean age 71.5±10.6 years), and 50 females and 25 males in the CS group (mean age 68.6±9.9 years). The observed sided effects were mild and their incidence was similar in the two groups. Patients in the HYADD 4 group reported significantly better WOMAC scores at 26 weeks. The patients improved in all considered outcomes after the injections, with a peak of therapeutic effect between 6 and 12 weeks. Patients in the HYADD 4 group obtained significantly better scores than the CS group up to 26 weeks. At the 1-year follow-up no statistically significant differences between treatments were detected.
CONCLUSIONS: HYADD 4 did not have significantly higher side effects when compared to CS injections and provided better short-term (but not long-term) control of symptoms in patients with mild to moderate knee osteoarthritis. Patients with less pain and dysfunction at baseline may be the best candidates for HYADD 4 injections.
<b>PURPOSE: </b>To assess the efficacy and safety of one and two intra-articular (IA) injections of the new viscosupplement, hylastan, compared with a single IA corticosteroid injection for pain due to knee osteoarthritis (OA). Hylastan is a high-molecular-weight hyaluronan derivative prepared from bacterial fermented sodium hyaluronate that was developed to remain in the joint for longer than most other viscosupplements.<b>METHODS: </b>This 6-month, double-blind, randomized, parallel group, multicenter trial enrolled patients aged ≥40 years who met American College of Rheumatology criteria for knee OA and had continued pain despite conservative treatment. Patients were randomized 1:1:1 to one of three arms: 2 × 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 × 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). Participants and evaluators were blinded to treatment. The primary clinical outcome measure was change from baseline in WOMAC A pain score over all postbaseline visits to Week 26.<b>RESULTS: </b>Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A: 2 × 4 mL hylastan -0.9 (-1.0, -0.7); 1 × 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all P < 0.0001 versus baseline. Changes in secondary outcomes (OMERACT-OARSI and WOMAC A responder rates, patient/clinical observer global assessments, and WOMAC A1 walking pain) were similar in all three arms. Target knee adverse events were comparable for all treatments.<b>CONCLUSIONS: </b>Both IA hylastan injection regimens were effective in relieving pain with an acceptable safety profile. IA hylastan did not show a difference versus IA corticosteroid; therefore, the hypothesis of superior pain relief was not met. Further research is needed to compare the efficacy and safety of hylastan with other viscosupplements.
<b>OBJECTIVE: </b>To compare NASHA hyaluronic acid gel as single-injection intra-articular (IA) treatment for knee osteoarthritis (OA) against methylprednisolone acetate (MPA).<b>DESIGN: </b>This was a prospective, multi-centre, randomized, active-controlled, double-blind, non-inferiority clinical trial. A unique, open-label extension phase (OLE) was undertaken to answer further important clinical questions. Subjects with painful unilateral knee OA were treated and followed for 26 weeks (blinded phase). All patients attending the clinic at 26 weeks were offered NASHA treatment, with a subsequent 26-week follow-up period (extension phase). The primary objective was to show non-inferiority of NASHA vs MPA in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain responder rate (percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points) at 12 weeks.<b>RESULTS: </b>In total, 442 participants were enrolled. The primary objective was met, with NASHA producing a non-inferior response rate vs MPA at 12 weeks (NASHA: 44.6%; MPA: 46.2%; difference [95% CI]: 1.6% [-11.2%; +7.9%]). Effect size for WOMAC pain, physical function and stiffness scores favoured NASHA over MPA from 12 to 26 weeks. In response to NASHA treatment at 26 weeks, sustained improvements were seen in WOMAC outcomes irrespective of initial treatment. No serious device-related adverse events (AEs) were reported.<b>CONCLUSIONS: </b>This study shows that single-injection NASHA was well tolerated and non-inferior to MPA at 12 weeks. The benefit of NASHA was maintained to 26 weeks while that of MPA declined. An injection of NASHA at 26 weeks conferred long-term improvements without increased sensitivity or risk of complications. STUDY IDENTIFIER: NCT01209364 (www.clinicaltrials.gov).
To assess the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis, sixty female patients with knee osteoarthritis were randomised to three weekly intra-articular injections of 30 mg sodium hyaluronate (Na HA) with a high molecular weight (1.0 to 2.9 million Da) or 40 mg 6-methylprednisolone acetate (6-MPA). The clinical assessments included pain at rest, at weight-bearing and on walking, Lequesne Index and active range of knee flexion. Assessments were done at baseline, at week 4, and at months 3 and 6. A significant decrease in VAS scores for pain at rest, at weight-bearing and pain on walking, and in Lequesne index was found in both groups at week 4 when compared to baseline and there was no significant differences between the two groups. However, at 3(rd) month improvement in all pain scores and Lequesne index was found in favour of hyaluronic acid. At 6(th), no significant difference was found between the treatment groups. Improvement in pain was accompanied by an increase in joint flexion at week 4 and at month 3 in both groups. Both treatments were well-tolerated. The results showed that both intra-articular hyaluronic acid and 6-MPA treatments provide clinically significant improvement and demonstrated that Na HA has a long-term beneficial effect in patients with knee osteoarthritis.
Corticosteroids have long represented the drugs of choice for intra-articular treatment of osteoarthritis (OA), but their use has drawbacks, indicating the need for alternatives devoid of these effects. This comparative study examined the clinical efficacy and the structural effects of intra-articular injections of sodium hyaluronate (HA) of molecular weight (MW) 500-730 kDa (one injection weekly for 5 weeks) versus methylprednisolone acetate (MP) (one injection weekly for 3 weeks) in the treatment knee OA. We studied 99 patients with knee OA, primary or secondary to a traumatic event, classified according to criteria of the American College of Rheumatology. Pain assessments by VAS and arthroscopic examinations of synovial membrane and cartilage were performed at baseline and 180 days after the start of the treatment. Arthroscopic features were evaluated under blind conditions. Initially, MP showed a more immediate beneficial clinical effect in reducing pain than HA, but after 180 days the symptomatic effect of HA was more long lasting than that of MP. Arthroscopic findings at day 180, in comparison with baseline conditions, showed that both drugs were decreased synovial membrane inflammation but HA was superior to MP in reducing the grade and extent of cartilage damage. HA of 500-730 kDa represents a valid alternative to corticosteroids in the intra-articular treatment of OA with a beneficial effect on the structural alterations. This study supports previous data on a potential structure-modifying activity of HA in OA of the knee.
The aim of the present study was to compare the clinical results and the quality of life in patients with symptomatic knee osteoarthritis randomised to either a new HA (HYADD 4) or corticosteroid (CS). A separate rationale was to evaluate the safety profile of HYADD 4.
METHODS:
All the patients presenting for unilateral symptomatic primary knee osteoarthritis were prospectively randomly assigned to receive 2 injections of either HYADD 4 or CS, and were evaluated before the injections and at 6, 12, 26 and 52 weeks. Primary end point was WOMAC score at 26 weeks; secondary end points were WOMAC score, VAS for pain, and SF-36 score at any time point.
RESULTS:
There were 53 females and 22 males in the HYADD 4 group (mean age 71.5±10.6 years), and 50 females and 25 males in the CS group (mean age 68.6±9.9 years). The observed sided effects were mild and their incidence was similar in the two groups. Patients in the HYADD 4 group reported significantly better WOMAC scores at 26 weeks. The patients improved in all considered outcomes after the injections, with a peak of therapeutic effect between 6 and 12 weeks. Patients in the HYADD 4 group obtained significantly better scores than the CS group up to 26 weeks. At the 1-year follow-up no statistically significant differences between treatments were detected.
CONCLUSIONS:
HYADD 4 did not have significantly higher side effects when compared to CS injections and provided better short-term (but not long-term) control of symptoms in patients with mild to moderate knee osteoarthritis. Patients with less pain and dysfunction at baseline may be the best candidates for HYADD 4 injections.
