Diflunisal in the treatment of osteoarthrosis: a double-blind study comparing diflunisal with ibuprofen

Summary

A double-blind trial was carried out in 37 patients with osteoarthrosis to compare the efficacy and tolerance of 250?mg diflunisal twice daily with that of 400?mg ibuprofen 3-times daily over an 8-week period. Rating scale assessments were made, at the end of a preceding 1-week wash-out period on placebo and at regular fixed intervals, of weight-bearing pain, night pain, a specific functional activity, and of the duration of inactivity stiffness. Patients' and physician's overall evaluations of response, taking side-effects into account, were made on completion of the study. The data collected indicated that in 30 patients completing the trial both treatments produced similar overall results and, with the exception of weight-bearing pain which appeared to be improved more in the ibuprofen group, diflunisal provided equal therapeutic benefit with fewer side-effects.     

Diflunisal in osteoarthrosis of the hip and knee

Summary

A double-blind randomized trial was carried out in 60 patients with osteoarthrosis of the hip or knee to assess the relative efficacy and tolerance of treatment with diflunisal twice daily (maximum 750?mg per day) or with aspirin given 4-times daily (maximum 3 g per day) over a period of 12 weeks. Clinical assessments were made on entry and at regular intervals of weight-bearing pain, night pain, specific function pain, inactivity stiffness, and range of joint movement. A considerable proportion of patients in both groups showed improvement in all parameters except for limitation of movement. The difference in response between the two groups was not statistically significant, neither was the patients' overall opinion of response to or clinician's assessment of therapeutic efficacy of either drug treatment at the end of the trial. Ten of the 29 patients in the aspirin group had to withdraw because of adverse reactions, mainly gastro-intestinal, compared with 4 of the 31 patients in the diflunisal group. The overall incidence of side-effects in all patients was lower in the diflunisal group, and those that were reported were less disturbing. At the end of the double-blind study, patients were given the option to continue with the particular drug treatment for a further two 13-week periods. More patients chose to remain on diflunisal than on aspirin at the end of each of the three periods and the difference was statistically significant.     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial

Summary

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250?mg diflunisal or 250?mg naproxen twice daily and this was increased by 250?mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly fewer side-effects than naproxen, the use of which was associated with a relatively high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

Double-blind parallel study of meptazinol versus diflunisal in the treatment of lumbago

Summary

Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200?mg meptazinol or 250?mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal.     

Comparison of slow-release indomethacin and diflunisal in patients with arthrosis

A double-blind, crossover study was carried out in 44 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of treatment with a new slow-release formulation of indomethacin (50 mg) with that of diflunisal (250 mg). After a 1-week wash-out period, patients were allocated at random to receive 2 tablets daily of one or other preparation for 6 weeks before being crossed over to the alternative drug for a further 6 weeks. Aspirin was allowed as a rescue analgesic throughout the study. Subjective assessments of pain and objective assessments of joint mobility were made before the start of treatment and at the end of each period, and details were recorded of rescue analgesic usage and any side-effects. Analysis of the results from 42 patients showed that whilst both treatments helped to alleviate pain, patients' overall evaluation of efficacy at the end of the study indicated that indomethacin was slightly more effective than diflunisal and there was a significant preference for indomethacin. Both drugs were well tolerated and none of the side-effects, reported in about 15% of patients on each drug, resulted in any withdrawals.     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial.

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250 mg diflunisal or 250 mg naproxen twice daily and this was increased by 250 mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

Comparison of slow-release indomethacin and diflunisal in patients with arthrosis

Summary

A double-blind, crossover study was carried out in 44 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of treatment with a new slow-release formulation of indomethacin (50?mg) with that of diflunisal (250?mg). After a 1-week wash-out period, patients were allocated at random to receive 2 tablets daily of one or other preparation for 6 weeks before being crossed over to the alternative drug for a further 6 weeks. Aspirin was allowed as a rescue analgesic throughout the study. Subjective assessments of pain and objective assessments of joint mobility were made before the start of treatment and at the end of each period, and details were recorded of rescue analgesic usage and any side-effects. Analysis of the results from 42 patients showed that whilst both treatments helped to alleviate pain, patients' overall evaluation of efficacy at the end of the study indicated that indomethacin was slightly more effective than dif lunisal and there was a significant preference for indomethacin. Both drugs were well tolerated and none of the side-effects, reported in about 15% of patients on each drug, resulted in any withdrawals.     

A double-blind crossover trial of diflunisal and naproxen in osteoarthritis

Fifty patients with osteoarthritis were studied in a double-blind, crossover trial of diflunisal (1000 mg daily) and naproxen (750 mg daily). In the 45 patients who completed the study, no significant difference was noted between the drugs in most of the parameters studied, including evening pain intensity and effectiveness rating by patient and investigator. There was a trend towards greater patient preference for diflunisal, although this trend did not reach statistical significance. Naproxen produced significantly fewer side-effects, although side-effects with both drugs were mild.     

The use of diflunisal in post-operative pain: a report of double-blind comparative trials in patients after meniscectomy.

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125 mg, 250 mg or 500 mg), aspirin (600 mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500 mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375 mg or 500 mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200 mg t.i.d.), hourly pain scores made on the first post-operative day showed that a single dose of 500 mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200 mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

Medical treatment of acute low back pain. Diflunisal compared with indomethacin in acute lumbago

Diflunisal and indomethacin were compared in patients with acute lumbago in a double-blind prospective clinical trial. The dosage of diflunisal was 500 mg twice daily (d-group) and the dosage of indomethacin 50 mg three times daily (i-group). Out of 133 patients, 66 were in the d-group and 67 in the i-group. They were followed up for a week. In addition to the patient's own daily evaluation of pain and functional disability, control visits were performed by the investigators on days 0, 3 and 7. Both of the test drugs were effective in the dosages used. Patients' pain was decreased, functional disability was improved and patients' subjective evaluation of treatment efficacy was very similar to that of the investigators. There were no differences as to the treatment efficacy, but reports of side-effects were slightly less (p less than 0.05) in the d-group than in the i-group. If patients who had no side-effects were compared, the efficacy of diflunisal was better than indomethacin (p less than 0.05). It can be said that indomethacin was essentially as effective as diflunisal, but at the expense of an increased frequency of side-effects. In the d-group two patients (3%) and in i-group six patients (9%) discontinued the therapy because of side-effects. In acute lumbago rapid relief of pain and other harmful symptoms hastens improvement. For such indications the choice of drug therapy in general practice should be based in particular on considerations of safety and lack of potential side-effects in addition to efficacy.     

The use of diflunisal in post-operative pain: a report of double-blind Comparative trials in patients after meniscectomy

Summary

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125?mg, 250?mg or 500?mg), aspirin (600?mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500?mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375?mg or 500?mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200?mg t.i.d.), hourly pain scores made on the first postoperative day showed that a single dose of 500?mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200?mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

Diflunisal in general practice

Summary

A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of diflunisal and aspirin in patients suffering from acute painful conditions such as sprains and strains, osteoarthritis, etc. Patients received either 250?mg or 500?mg diflunisal twice daily, or 600?mg aspirin 4-times daily for 5 days. The results of subjective assessments of pain relief from the daily records of 1902 patients (967 on diflunisal, 935 on aspirin), and the overall assessment of response by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-effects were more common and more severe in patients receiving aspirin, and more often led to withdrawal of treatment.     

Difunisal in general practice.

A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of difunisal and aspirin in patients suffering from acute painful conditions such as sprains and trains, osteoarthritis, etc. Patients received either 250 mg or 500 mg difunisal twice daily, or 600 mg aspirin 4-times daily for 5 days. The results of subjective assessments of pain relief from the daily records of 1902 patients (967 on diflunisal, 935 on aspirin), and the overall assessment of response by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-effects were more common and more severe in patients receiving aspirin, and more often led to withdrawal of treatment.     

Azapropazone in arthritis: a long-term treatment

A long-term open assessment of azapropazone (900 mg to 1200 mg daily) was carried out in 51 patients suffering from osteoarthritis for periods of up to 1 year. Of these patients, 70% completed 9 to 12 months of treatment. Clinical assessments were made before and during the study of pain on motion or weight bearing, night pain, functional activity, morning stiffness, doctor's overall assessment, patients' overall assessment, and details of side-effects recorded. There were statistically significant improvements in the mean rating scores for each of the clinical assessments and these became apparent at 1 month, maximal at 3 to 6 months and persisted at the same level to the end of the trial. There were no side-effects recorded at any period of the trial in 30 (59%) patients. When side-effects did occur they were mild in 12 (24%), moderate in 3 (6%) and severe in 6 (12%) patients. The most frequent side-effects were related to the gastro-intestinal tract and gastric pain occurred in 7 (14%) patients, whilst rash or eczema occurred in 4 (8%) patients. It was concluded that, for the patients in the trial, long-term treatment with azapropazone was a useful and effective procedure.     

A controlled study of diflunisal in Sprains and Strains

Summary

A preliminary double-blind, randomized trial was carried out in general practice to compare the efficacy of treatment with diflunisal (500?mg) twice daily and a combination of dextropropoxyphene (65?mg) plus paracetamol (650?mg) 3-times daily for 3 days in relieving pain associated with strains and sprains. Analysis of the results from 51 patients showed that both treatments were equally effective in relieving spontaneous pain and pain on movement after 1 and 3 days, and there were no differences between the two groups in patients' overall evaluation of treatment or physicians' assessment of therapeutic response. Both treatments were well tolerated during the short-term period of the trial.     

A comparative trial of ketoprofen and ibuprofen in patients with rheumatic disease.

A comparative controlled study was carried out in 40 patients suffering from rheumatoid arthritis, osteoarthrosis or ankylosing spondylitis to assess the efficacy of ketoprofen and ibuprofen. Patients were allocated at random to receive either 100 mg ketoprofen twice daily or 400 mg ibuprofen 3-times daily over a period of 3 months. Subjective overall assessments of symptoms, based on rating scale scores for pain, duration of morning stiffness and inflammation, showed that there was a greater, more rapid and more sustained improvement in those patients treated with ketoprofen. Measurements of inflamed joint size and of grip strength also improved more with ketoprofen than with ibuprofen. Side-effects, notably nausea, epigastric discomfort and abdominal pain, were more frequent and severe with ketoprofen, leading to the withdrawal of 2 patients in the early stage of the trial, and were probably related to the high dosage used. Three patients receiving ibuprofen needed 7 injections of ACTH to control their symptoms.     

Diclofenac sodium in the treatment of painful stiff shoulder

A double-blind controlled, between-patient trial was carried out in 40 patients with painful stiff shoulder to compare the effect of treatment with either 50 mg diclofenac sodium or 400 mg ibuprofen given 3-times daily for 2 weeks. The results of assessments made before and after treatment showed that although both drugs produced some improvement no statistically significant differences between the two groups in terms of pain relief or the range of movement were evident. The incidence of side-effects was also similar.     

Differential dosing study of pirazolac, a new non-steroidal anti-inflammatory agent, in patients with rheumatoid arthritis

Twenty-four patients with classical or definite rheumatoid arthritis participated in a 4-week double-blind crossover study to compare the effectiveness of two different dosage regimens of pirazolac. Patients were allocated at random to receive 2-weeks' treatment with either 300 mg pirazolac in the morning and 600 mg at night or 450 mg pirazolac given morning and evening, and were then crossed over to the alternative regimen for a further 2 weeks. Physician assessments of disease activity were carried out on entry and at the end of each treatment period, and patients kept a daily record of visual analogue scale scores for pain and stiffness. The results showed that both dosage regimens of pirazolac produced a significant improvement in the parameters assessed, but the difference between the two regimens was not significant. However, overall assessment at the end of the trial by the 23 patients who completed the study showed that 14 preferred the 300/600 mg regimen compared with 7 who preferred the 450/450 mg regimen: 2 patients considered both regimens equally effective. Pirazolac was relatively well tolerated, only a few patients reporting gastro-intestinal (2) and skin (3) side-effects during the trial period.