Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip. A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect. Mixture of Arnebia euchroma and Matricaria chamomilla (Marhame-Mafasel) for pain relief of osteoarthritis of the knee - a two-treatment, two-period crossover trial. Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip. Intra-articular hyaluronan injections for the treatment of osteoarthritis of the knee: a randomized, double blind, placebo controlled study. Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis.
One of the objectives of symptomatic slow-acting drugs for osteoarthritis is to reduce the need for drugs with a less favorable safety profile, mainly analgesics and nonsteroidal antiinflammatory drugs (NSAIDs). We conducted a three-month, prospective, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of avocado/soybean unsaponifiables in terms of NSAID use reduction. Patients with primary femorotibial or hip osteoarthritis (OA) (ACR criteria and Kellgren-Lawrence radiological stage IB, II, or III) of at least six months' duration with regular pain for more than three months requiring therapy with NSAID (visual analog scale score > or = 25 mm and Lequesne's index on therapy > or = 4) were given one capsule per day of avocado/soybean unsaponifiables or a placebo for three months. During the first 45 days, patients in both groups were also given one of seven predefined NSAIDs. The primary efficacy criteria was the rate of patients taking back a NSAID and the delay before re-intake. Secondary efficacy criteria were the total dose of NSAID, overall ratings by the patient and by the physician, the visual analog scale pain score and the functional index. Of the 164 included patients, 163 were evaluable, 80 in the active drug group and 83 in the placebo group. Mean age was 62.9 +/- 8.8 years. The diagnosis was femorotibial OA in 101 patients and hip OA in 62. Data were collected on day 45 in 153 patients (77 on the active drug and 76 on the placebo). The number of patients who took back NSAID therapy was significantly smaller in the group treated by avocado/soybean unsaponifiables (33; 43.4%) than in the placebo group (53; 69.7%) (P < 0.001). Also, beyond day 54, the time spent off NSAID therapy was shorter in the placebo group. The functional index showed a significantly greater improvement in the active drug group (-2.3 +/- 2.6) than in the placebo group (-1.0 +/- 2.6) (P < 0.01). Pain scores over time were similar in the two groups. Overall patient ratings were significantly better in the active drug group (P < 0.01). Safety was oggd in both groups. After six weeks, avocado/soybean unsaponifiables reduced the need for NSAID in patients with lower limb OA. To assess the efficacy and safety of avocado/soybean unsaponifiables (ASU) in the treatment of patients with symptomatic osteoarthritis (OA) of the knee or hip, as well as the potential residual effects of ASU after stopping treatment, to determine whether ASU might be a symptomatic slow-acting drug for the treatment of OA.
                One hundred sixty-four patients with regular, painful, primary OA of the knee (n = 114) or hip (n = 50) entered a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial with a 6-month treatment period and a 2-month posttreatment followup. A 15-day washout period for nonsteroidal antiinflammatory drugs (NSAIDs) preceded the study. Efficacy was judged according to 1) Lequesne's functional index (LFI) and 2) pain on Huskisson's visual analog scale (VAS; 100-mm scale), intake of NSAIDs/analgesics, and overall disability score (by 100-mm VAS).
                Eighty-five patients received ASU; 79 received placebo. One hundred forty-four patients were evaluable at month 6 (75 taking ASU; 69 taking placebo). The mean +/- SEM LFI score decreased from 9.7 +/- 0.3 to 6.8 +/- 0.4 in the ASU group and from 9.4 +/- 0.3 to 8.9 +/- 0.4 in the placebo group (P < 0.001 for intergroup difference at month 6). Pain decreased from 56.1 +/- 1.6 mm to 35.3 +/- 2.3 in the ASU group and from 56.1 +/- 1.8 mm to 45.7 +/- 2.6 in the placebo group (P = 0.003 at month 6). NSAID consumption was slightly lower in the ASU group. Fewer patients in the ASU group required NSAIDs (48%, versus 63% in the placebo group; P = 0.054). The success rate was 39% in the ASU group and 18% in the placebo group. Overall functional disability was significantly reduced in the ASU group. Improvement appeared more marked in patients with hip OA. A residual effect was observed at month 8. Tolerance was good to excellent for most patients.
                ASU treatment showed significant symptomatic efficacy over placebo in the treatment of OA, acting from month 2 and showing a persistent effect after the end of treatment. Osteoarthritis is the most prevalent chronic non-infective joint arthritis. Because of its chronic disease nature, local drugs are preferred due to lower complications. In the present study, the new herbal pomade Marhame-Mafasel for knee osteoarthritis was used in a double-blind crossover trial. The aim of the study was to assess the efficacy and safety of Marhame-Mafasel pomade, which consists of several medical herbs including Arnebia euchroma and Matricaria chamomilla, in osteoarthritis of the knee.
                This study was a placebo-controlled double-blind crossover trial. Forty-two patients with pain associated with osteoarthritis of the knee (diagnosed by criteria of the European League against Rheumatism and physical examination) were drawn from patients attending the Clinic of Mostafa-Khomeini Hospital. In this study we assessed efficacy (analgesic effect and improved function) of herbal pomade Marhame-Mafasel, which was used locally in patients with primary osteoarthritis of the knee over three weeks. The instrument of the study was the Western Ontario and McMaster Universities (WOMAC) LK3.1 standard questionnaires.
                The participants in each group were 21 patients; 30 (71.4%) were women and 12 (28.6%) of them were men. The participants were between 40 and 76 years old. Six patients had mild arthritis, 15 had moderate arthritis and 21 had severe arthritis. The positive analgesic effect of the herbal pomade Marhame-Mafasel in primary knee osteoarthritis was proven. The herbal joint pomade Marhame-Mafasel had a significantly greater mean change in score compared to the placebo group for osteoarthritis severity (p < 0.05).
                Herbal pomade Marhame-Mafasel in comparison to placebo has more effect on reduction of pain of primary knee osteoarthritis. To evaluate the efficacy and safety of diacerein, a drug with interleukin-1beta--inhibitory activity in vitro, in patients with knee osteoarthritis (OA).
                A total of 484 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 16-week, randomized, double-blind, placebo-controlled, parallel study group with 3 diacerein dosages of 50 mg/day, 100 mg/day, and 150 mg/day (administered twice daily).
                In the intent-to-treat population, 100 mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement). Significant improvement (P < 0.05) was also observed for the secondary criteria, which included the Western Ontario and McMaster Universities OA Index (WOMAC), the WOMAC subscores, and the VAS assessment of handicap. In patients treated with diacerein dosages of 50 mg/day and 150 mg/day, favorable but not significant results were observed for the primary criterion. The best daily dosage of diacerein, calculated from the effect on the VAS assessment of pain on movement, was 90.1 mg. In the per-protocol population, the analysis of the primary criterion showed significant dose-dependent differences (P < 0.05) between each of the 3 diacerein dosages and the placebo. No differences were observed among the 3 diacerein groups. A significantly higher incidence (P < 0.05) of adverse events (AEs), as well as a higher rate of dropoout due to AEs, was observed in patients treated with 150 mg/day diacerein versus those treated with placebo, 50 mg/day diacerein, or 100 mg/day diacerein. Mild-to-moderate transient changes in bowel habits were the most frequent AEs, increasing with the dosage.
                Diacerein, a drug for the treatment of OA, was shown to be an effective treatment for symptoms in patients with knee OA. Taking into account both efficacy and safety, the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day (50 mg twice daily). To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
                We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS).
                OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA).
                The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA. To evaluate the ability of diacerein, an interleukin-1beta inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA).
                In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1-mm-graduated magnifying glass.
                Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent-to-treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean +/- SD 0.18 +/- 0.25 mm/year versus 0.23 +/- 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel habits.
                This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation. Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers.
                A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study.
                The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups. To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA).
                In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).
                In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was -2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events.
                Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA. In a double-blind, randomized, multicentre clinical study, the efficacy and tolerance of a herbal medicine product, Harpadol (6 capsules/day, each containing 435 mg of powdered cryoground powder Harpagophytum procumbens), was compared with diacerhein 100 mg/day in the treatment, for 4 months, of 122 patients suffering from osteoarthritis of the knee and hip. Assessments of pain and functional disability were made on a 10 cm horizontal visual analogue scale; severity of osteoarthritis was evaluated by Lequesne's index. Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments. Similarly, there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein. At completion of the study, patients taking Harpadol were using significantly less NSAIDs and antalgic drugs. The frequency of adverse events was significantly lower in the Harpadol group. The most frequent event reported was diarrhea, occurring in 8.1% and 26.7% of Harpadol and diacerhein patients respectively. The global tolerance assessment by patients at the end of treatment favoured Harpadol. The results of this study demonstrate that Harpadol is comparable in efficacy and superior in safety to diacerhein.
The evidence for avocado-soybean unsaponifiables in the treatment of osteoarthritis is convincing but evidence for the other herbal interventions is insufficient to either recommend or discourage their use.