Relationship of plasma salicylate levels to pain relief with two different Salicylates

Summary

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250?mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain-relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.     

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee.

A short-term, double-blind controlled crossover study was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the effectiveness and tolerance of salsalate and aspirin. After a 1-week placebo washout period, patients received either 3 g salsalate per day or 3.6 g soluble aspirin per day for 2 weeks before being crossed over to the alternative treatment. Paracetamol was used as a rescue analgesic. The results of clinical assessments of pain, stiffness and sleep disturbance, using visual analogue scales, showed that salsalate produced a comparable clinical improvement to that with aspirin, and similar serum salicylate levels. Salsalate, however, was significantly superior to aspirin with regard to side-effects and faecal occult blood loss.     

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee

Summary

A short-term, double-blind controlled crossover study was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the effectiveness and tolerance of salsalate and aspirin. After a 1-week placebo washout period, patients received either 3 g salsalate per day or 3.6 g soluble aspirin per day for 2 weeks before being crossed over to the alternative treatment. Paracetamol was used as a rescue analgesic. The results of clinical assessments of pain, stiffness and sleep disturbance, using visual analogue scales, showed that salsalate produced a comparable clinical improvement to that with aspirin, and similar serum salicylate levels. Salsalate, however, was significantly superior to aspirin with regard to side-effects and faecal occult blood loss.     

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.     

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.     

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.     

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 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.     

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 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.     

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.     

Fecal blood loss and plasma salicylate study of salicylsalicylic acid and aspirin.

Using a placebo-controlled methodology, 20 healthy volunteers housed in a clinical research facility for 23 days were studied for fecal blood loss and plasma salicylate levels after taking salsalate (salicylsalicylic acid) or aspirin. Daily dosages were 3000 mg salsalate or 3900 mg aspirin. Aspirin produced statistically significant gastrointestinal blood loss over control levels and over that produced by salsalate (P less than 0.01). Blood loss with salsalate was not different than that with placebo. Despite the intentional disparity of dosages between the two drugs, plasma salicylate levels were not statistically different. Side effects occurred at about equal frequency with either drug. Most prominent were headache and nausea. However, concomitant upper respiratory infection in 12 subjects rendered interpretation difficult.     

A double-blind comparative study of 150 mg flurbiprofen daily and 75 mg indomethacin daily in the treatment of osteoarthrosis of the hip joint.

Thirty patients with osteoarthrosis of the hip were studied in a double-blind crossover comparison of 150 mg flurbiprofen daily and 75 mg indomethacin daily, each drug being given for 2 weeks separated by a wash-out period of 1 week on placebo. Statistical analysis of the results from 26 patients with complete records showed that both drugs produced statistically significant improvements over baseline after 1 and 2 weeks in assessments of severity of pain, night pain, duration of morning stiffness, and intermalleolar straddle. No statistical differences, however, were found between the two drugs. There were no reports of side-effects with flurbiprofen, but 6 reports from 3 patients whilst receiving indomethacin.     

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.     

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.     

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.     

Efficacy and tolerance of flurbiprofen in the elderly using liquid and tablet formulations.

An open study was carried out in 40 elderly patients suffering from osteoarthrosis of the hip to assess the effectiveness of 200 mg flurbiprofen daily, fiven either in tablet or liquid suspension form, over a period of 4 weeks. Statistical evaluation of the results in the 19 patients admitted to analysis showed that flurbiprofen produced significant improvement in daytime and overnight pain, and did not impair their mental status, as assessed on a modified Goldfarb scale. No significant differences were found between the response of the two groups, except for severity of night pain. Fourteen of the 19 patients included in the analysis reported side-effects, as did 18 of the 21 patients who were excluded. Only 7 patients (4 on tablets, 3 on liquid), however, were withdrawn from the trial for this reason.     

Efficacy and tolerance of flurbiprofen in the elderly using liquid and tablet formulations

Summary

An open study was carried out in 40 elderly patients suffering from osteoarthrosis of the hip to assess the effectiveness of 200?mg flurbiprofen daily, given either in tablet or liquid suspension form, over a period of 4 weeks. Statistical evaluation of the results in the 19 patients admitted to analysis showed that flurbiprofen produced significant improvement in daytime and overnight pain, and did not impair their mental status, as assessed on a modified Goldfarb scale. No significant differences were found between the response of the two groups, except for severity of night pain. Fourteen of the 19 patients included in the analysis reported side-effects, as did 18 of the 21 patients who were excluded. Only 7 patients (4 on tablets, 3 on liquid), however, were withdrawn from the trial for this reason.     

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.     

Comparison of a slow-release indomethacin tablet and naproxen in osteoarthrosis

A double-blind, crossover study was performed in 21 out-patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of a new slow-release formulation (multiple units dose preparation) of indomethacin (50 mg) with those of naproxen (250 mg). After a wash-out period of 1 week, the patients were randomized to receive 2 tablets daily of one or other preparation for 3 weeks. This was followed by another wash-out period of 1 week, whereafter the patients were crossed over to the alternative drug for another 3 weeks. Subjective assessments of pain and objective assessment of joint mobility and the use of acetylsalicylic acid as rescue analgesic were used to evaluate the efficacy of the treatment. Analysis of results from 19 patients showed that both drugs effectively alleviated pain, and there was no difference between indomethacin and naproxen in this respect. There were 2 withdrawals, 1 on naproxen due to inefficacy and 1 on indomethacin due to gastro-intestinal side-effects. Otherwise, the drugs were well tolerated and side-effects occurred to the same extent on both drugs. This study confirms the good efficacy and tolerability of the new slow-release indomethacin preparation.