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

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

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 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.     

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.     

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.     

Section 1 A Comparative Study of Ibuprofen (‘Brufen’) And Indomethacin in Uncomplicated Arthrosis

Summary

A double-blind crossover comparison of 1200?mg. ibuprofen daily and 75?mg. indomethacin daily was carried out over an 8-week period in 39 patients with uncomplicated osteoarthrosis. The results from objective assessments of joint measurement were similar for both drugs. Only 16 patients noted any difference between the two treatment periods, and preferences, as assessed by physician and patients, were about equally in favour of each drug. There was, however, a marked order effect with preference for the second 4-week treatment period. Fewer patients reported side-effects when receiving ibuprofen.     

A crossover clinical trial of piroxicam,indomethacin and ibuprofen in rheumatoid arthritis

Summary

A single-blind, crossover trial was carried out in 24 patients with definite or classical rheumatoid arthritis to compare the effectiveness and tolerability of piroxicam (20?mg once daily) with that of indoniethacin (25?mg 3-times daily), ibuprofen (400?mg 3-times daily) and placebo. Each drug was given in random order for a period of 1 week. Pain, joint tenderness and morning stiffness decreased and grip strength increased with piroxicam compared to placebo; no statistically significant difference could be found between piroxicam and the two other active agents. A reduction in joint circumference could not be demonstrated with piroxicam or ibuprofen but most patients did not have reducible swelling in their finger joints. Piroxicam was just as effective as the other two drugs overall, but fewer side-effects were noted with piroxicam.     

Azapropazone in arthritis: a long-term treatment

Summary

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, junctional 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.     

Diflunisal in the management of sprains

Summary

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500?mg diflunisal twice daily or 200?mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed that by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.     

Indoprofen versus ibuprofen in osteoarthrosis: a short-term,double-blind,crossover trial

Summary

A double-blind, crossover, short-term clinical trial was carried out in osteoarthrosis to compare the activity of two non-steroidal anti-inflammatory drugs. Twenty-four patients were given orally, in sequence, 600?mg indoprofen daily and 1200?mg ibuprofen daily, or vice-versa, for 1 week with no interval between treatment periods. Pain, quality of sleep, and overall effectiveness were recorded at the end of each week by inviting patients to express a score on a simple rating scale. Finally, patients were asked to express a preference for one treatment or the other. Significant improvement was observed in all parameters following treatment with both drugs. The distribution of score differences between indoprofen and ibuprofen was in favour of the former in all measurements; statistical analysis, however, demonstrated a significant superiority of indoprofen only for pain elicited by passive motion. The patients' preferences were also in favour of indoprofen, though not attaining statistical significance. Indoprofen was well tolerated, and no side-effects were observed. While on treatment with ibuprofen, I patient had to be withdrawn from the study because of gastric intolerance and 2 further patients had transient skin rashes.     

Section 3 Clinical studies of ibuprofen

Summary

Essential data from 3 studies on ibuprofen are presented. In an open multi-centre general practice study in 571 patients with osteoarthrosis, rheumatoid arthritis and various musculoskeletal conditions, a favourable response was obtained in 77% treatedwith800mg.to1200mg.ibuprofen daily overa 1-month period. In a double-blind crossover comparison of 1200?mg. ibuprofen with 75?mg. indomethacin in 24 patients with osteoarthrosis of the spine, both drugs proved to be equally effective but side-effects were less with ibuprofen. The final study in 21 patients showed that ibuprofen was more effective thanplacebo in controlling post-operative pain, trismus and oedema following minor oral surgical procedures.     

Section 2 Ibuprofen in the long-term treatment of coxarthrosis

Summary

In an open controlled trial of ibuprofen in the long-term treatment of osteoarthrosis of the hip, 35 patients received 1200?mg. ibuprofen daily over a period of 6 months. Seven patients discontinued treatment after 2 months because of remission of all symptoms and 7 others were withdrawn (2 due to side-effects, 5 for non-medical reasons). Subjective and objective assessments were carried out at monthly intervals. The results showed that pain was significantly reduced, particularly during the first 2 months, and there was a marked reduction in the need for additional analgesics. There was also a significant improvement in joint mobility within the first few months of treatment. Ibuprofen was well tolerated and side-effects were minimal.     

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

Summary

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.     

Section 1 Ibuprofen in osteoarthritis

Summary

In a multi-centre, double-blind crossover trial of 1800?mg. ibuprofen daily, 3.6 g. aspirin daily, and placebo, 437 patients with osteoarthrosis affecting various large joints were studied for 8 weeks. Judged by patient preference for drug or placebo treatment periods, both drugs were found to be superior to placebo and about equally as effective in relieving pain and in improving the ability to perform a selected activity. Gastro-intestinal side-effects were substantially fewer in patients receiving ibuprofen.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy

Summary

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125?mg, 250?mg, or 500?mg), aspirin (600?mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500?mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

Clinical therapeutic evaluation of methylcysteine hydrochloride in patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control

Summary

A double-blind, between-patient, placebo controlled trial was carried out to investigate the effects of methylcysteine hydrochloride in patients with chronic obstructive bronchitis. After a 2-week washout period on placebo, 30 patients were allocated at random to treatment for 6 weeks with either methylcysteine (1200?mg daily in Week 1, 800?mg daily in Week 2, then 600?mg daily) or with identical placebo tablets on the same regimen. During the post-treatment period, all patients returned to a single-blind placebo regimen (6 tablets daily) for a further 14 days. Assessments were made at the start, at regular intervals during the trial, and at the end of the post-treatment period, of subjective and objective measures of clinical response, and measurements of pulmonary function and certain physico-chemical properties of sputum. The results showed that methylcysteine increased sputum volume, reduced the viscidity of sputum, and significantly improved the subjective assessments of ease of expectoration and severity and frequency of cough, leading to a definite improvement in the patients' clinical state. No side-effects of clinical significance were reported and no abnormalities were found in any of the haematological, hepatic and renal function tests carried out.