Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. 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. Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy. [Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes]. Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Study of efficacy and safety of a new local cream ('healer') in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study. Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis. Intraindividual differences in pain relief and functional improvement in osteoarthritis with diclofenac or tramadol.
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 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. Seventy-two patients complaining of abdominal pain were studied in a double blind trial with otilonium bromide (OB) (40 mg tid or placebo). In our patients we performed, before and after the treatment, a clinical evaluation (symptom variations) and functional studies (sigmoid manometry during bowel distension). As regards clinical parameters, otilonium bromide significantly reduced abdominal pain and bloating and significantly increased (p less than 0.02) the pain threshold. However the comparison with the placebo group did not show any difference between the two groups. Sigmoid motility during distension was significantly reduced (p less than 0.05) in OB group, whereas it did not change in the placebo group. We can conclude that, in irritable bowel syndrome (IBS) patients, OB is able to improve symptoms and to reduce stimulated motor activity of the sigmoid. The use of nonsteroidal anti-inflammatory drugs (NSAID) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone. This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen. From September through December of 1986, 256 patients participated in a multicenter, controlled, randomized double-blind trial which compared the clinical efficacy of diclofenac (50 mg) with a combined therapy of diclofenac (50 mg) and vitamins B1, B6, and B12 (thiamine nitrate, pyridoxine hydrochloride, and cyanocobalamine, resp.; in dosages of 50 mg, 50 mg, and 0.25 mg, resp.). Patients were treated with 3 X 1 capsule daily for a maximum of two weeks, having the option to terminate participation in the trial after 1 week in the event of total pain relief. The data of 238 patients were able to be included in the evaluation. 29 patients opted to discontinue therapy due to remission on symptoms. Nineteen (65.6%) of these patients belonged to the combined therapy group, the other 10 (34.4%) having taken diclofenac alone; this difference is statistically significant (p less than 0.05). An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which, in addition to their subjective feedback, was reflected in the test results of the "Hoppe Pain Questionnaire (HPQ)." All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone. Moreover, after 3 days of therapy the "sensory" pain factor "sharpness" improved significantly. Undesirable side-effects were documented with 39 patients, 14 of them having discontinued therapy for this reason. No statistically significant difference could be determined within this group with regard to therapy. The study results document the positive influence of B-vitamins on painful symptoms and indicate that less NSAID is needed for pain relief when combined with B-vitamins. To assess the efficacy and safety of a diclofenac hydroxyethylpyrrolidine (DHEP) patch in the treatment of symptomatic osteoarthritis (OA) of the knee joint.
                A double-blind, randomised, placebo-controlled trial was carried out on 103 outpatients for 2 weeks. The main efficacy parameters were spontaneous pain and Lequesne's Index. Secondary endpoints were walking time over a standard distance, global assessment of efficacy and tolerability, and paracetamol consumption.
                The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy. For these parameters the difference between groups was statistically significant in favour of the DHEP patch. Adverse reactions were seen in a small number of probands and were similar in both groups.
                The results of this trial suggest that the DHEP patch appears to be an effective and safe treatment for patients suffering from symptomatic knee 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. To determine the efficacy and safety of 'healer' cream as monotherapy in the treatment of acute and chronic anal fissure.
                A prospective, randomized, single blinded, comparative trial.
                Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with 'healer' local cream application 3 times daily; group B: treated with nitroglycerine 0.25% local cream 3 times daily; group C: treated with a lidocaine 2% cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications.
                The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with 'healer' isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with 'healer' was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in 'healer' group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90%) of 20 patients in the 'healer' group and in 12 (60%) of 20 in the nitroglycerin group, while only 6 (30%) of patients treated with lidocaine cream had their fissures healed by the 30 days treatment. Chi square = 15 (P = 0.001).
                'Healer' is a promising effective and safe line of treatment in acute and chronic anal fissure. The characteristic pharmacokinetics of isosorbide-di-nitrate leads to a better effect than nitroglycerin in healing (more prolonged action). Also the less fast absorption than nitroglycerin leading to a smoother dose concentration curve, may be the cause that headache is less frequent and less severe in 'healer' treatment versus nitroglycerin. The safe and efficacious use of Pycnogenol (French maritime pine bark extract) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA). The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind, placebo-controlled, randomly allocated trial with patients suffering from knee osteoarthritis stages I and II.
                100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo. Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period. Patients filled the Western Ontario and Mc Masters University (WOMAC) questionnaire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity.
                Following treatment with Pycnogenol patients reported an improvement of WOMAC index (p < 0.05), and a significant alleviation of pain by visual analogue scale (p < 0.04), the placebo had no effect. The use of analgesics diminished in the verum group but increased under the placebo. Treatment with Pycnogenol was well tolerated.
                Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs. To investigate how individual patients with painful osteoarthritis (OA) respond to the non-steroidal anti-inflammatory drug (NSAID) diclofenac and the centrally acting analgesic tramadol when individual on-demand dose titration is allowed. In addition, we studied whether the differences in the mode of action of the different analgesics were important for functional outcome in OA patients.
                This was performed as a double-blind, crossover, randomised study in 60 patients with OA of the hip (19 patients) or knee (41 patients) without clinical joint inflammation. Patients received either tramadol (50 to 100mg up to three times daily, on demand) for 4 weeks, followed by diclofenac (25 to 50mg up to three times daily, on demand) for 4 weeks, or vice versa. The multidimensional 'Western Ontario and McMaster Universities Osteoarthritis Index' (WOMAC) questionnaire (pain, stiffness and functional impairment) was used to assess the effect of the drugs on pain and functional capability.
                54 patients completed both study periods. The mean (+/- SD) daily dose of tramadol consumed was 164.8mg (+/- 54.1mg) and that of diclofenac was 86.9mg (+/- 21.4mg). Both treatments modestly improved median pain intensity, paralleled by an improvement in functional parameters, and there were no statistically significant differences between the groups. However, individual treatment effects varied greatly, and within individual patients there were considerable variations in analgesic effectiveness between the two treatments. Consistently, pain relief correlated linearly with functional improvement. More patients reported adverse events with tramadol than with diclofenac (20 vs 3%, p = 0.0056), but there was no difference in adverse event-related withdrawals (p = 0.69).
                OA patients' response to analgesic treatment was highly individual and the response to one drug was not predictive of that to another drug. A significant proportion of patients were not treated satisfactorily with diclofenac or tramadol alone. The results obtained from a descriptive analysis of group effects (means, medians) were inappropriate for drawing conclusions on individual treatment benefits. Improvement of functional capability apparently was a consequence of pain relief. Effective pain relief should therefore be the main therapeutic goal in patients with OA where inflammation is less prominent.
There is 'gold' level evidence that diacerein has a small, consistent benefit in improvement in pain. Further research is necessary to confirm the short and long-term effectiveness and toxicity of diacerein therapy in OA.