Efficacy and tolerability of a topical NSAID patch (local action transcutaneous flurbiprofen) and oral diclofenac in the treatment of soft-tissue rheumatism

Summary The efficacy and safety of local action transcutaneous flurbiprofen 40 mg [flurbiprofen LAT] patches and diclofenac sodium tablets, 50 mg b.d., were compared in an open, multicentre, randomized, parallel-group study in patients with soft-tissue rheumatism. Patches were replaced at 12-hourly intervals. Clinical assessments were performed after 7 and 14 days of treatment. Fifty-six patients were treated with flurbiprofen LAT and 53 with diclofenac. Six withdrawals (three from each group) occurred during the treatment period.A statistically significant difference was observed in favour of flurbiprofen LAT for the principal measure, namely the investigator's opinion of overall change in clinical condition: 49/53 (92%) patients treated with flurbiprofen LAT had improved by day 14 compared with 36/49 (73%) patients receiving diclofenac sodium (p=0.03; eligible dataset). There were also statistically significant differences in favour of flurbiprofen LAT for the investigator's assessments of the overall severity of the clinical condition (p=0.03; eligible dataset), for the severity of pain at the region treated (p=0.04; intent-to-treat), and for the severity of tenderness (p<0.001; intent-to-treat). Supplementary analgesia (paracetamol) was required by two patients in the flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT in the average daily consumption of paracetamol was significant (p=0.04). The patients' assessment of severity of pain on movement also favoured flurbiprofen LAT (p =0.049; eligible dataset), but there were no statistically significant differences in day or night pain or quality of sleep. For the patients' opinion of treatment there was, however, a statistically significant difference in favour of flurbiprofen LAT (p=0.02). Of the patients receiving flurbiprofen LAT, 94% regarded it as a convenient form of treatment.With respect to tolerability 8/56 (14%) patients applying flurbiprofen patches reported a total of nine adverse effects (AEs) (mainly local, mild skin irritations), vs 9/52 (17%) patients receiving diclofenac, who reported 12 AEs. Most AEs in the enteric-coated diclofenac group were of a gastrointestinal nature (one of which was severe). In terms of the proportion of patients reporting AEs related to the digestive system, there was a statistically significant difference in favour of flurbiprofen LAT (p=0.011).In conclusion, local treatment of soft-tissue rheumatism with flurbiprofen LAT was demonstrably superior to benchmark oral therapy with diclofenac sodium over a 2-week period in terms of both efficacy and gastrointestinal tolerability. Flurbiprofen LAT provided both an effective and convenient form of topical SAID treatment.     

'Diaphragmlike' stricture and ulcer of the colon during diclofenac treatment.

Diclofenac sodium is a widely used enteric-coated nonsteroidal anti-inflammatory drug. We describe a woman with Hemoccult-positive stools and iron deficiency anemia who developed both a colonic ulcer and a "diaphragm-like" colonic stricture while taking enteric-coated diclofenac. These lesions were evident on colonoscopy but not on barium studies. Biopsy specimens of the ulcer and stricture revealed particulate matter that was indistinguishable from diclofenac pill fragments by electron microscopy. Discontinuation of diclofenac therapy resulted in resolution of anemia and Hemoccult-positive stools. We conclude that (1) enteric-coated diclofenac is associated with both colonic ulcers and diaphragm-like colonic strictures; (2) the pathophysiologic mechanism for the development of both ulcers and strictures may involve a direct action of diclofenac within these lesions; (3) colonoscopy may be superior to barium studies in evaluating patients receiving diclofenac who have iron deficiency anemia and/or Hemoccult-positive stools.     

Pharmacokinetics and biological availability of diclofenac preparations following intramuscular injection of 75 mg and oral administration of 150 mg of active drug

Four different formulations of diclofenac sodium, a widely used NSAID, were administered to eight healthy young volunteers in a cross-over study, according to a latin-square design. The subjects received either 75 mg as intramuscular injections or 150 mg as enteric-coated tablets. Following administration, blood samples were drawn and analysed for unchanged diclofenac, employing HPLC. 72.9% of the oral dose was absorbed with an average lag-time of 2.2 h. Peak plasma concentrations amounted to 2.9 micrograms/ml after 3.1 h, as compared to 2.15 micrograms/ml, 20-30 min following an intramuscular injection of 75 mg. Diclofenac sodium was excreted with an average half-life of 1.15 h. The bioavailability of the three i.m. injectable solutions, as calculated from the area under the curve (AUC), did not differ significantly. The results suggest that i.m. injectable diclofenac sodium provides fast drug liberation suitable for acute analgesic treatment, although the general risk of i.m. injections, as well as the very rare risk of protracted anaphylactic shocks, has to be taken into account. Despite the high variability of absorption, peak plasma concentrations and bioavailability, the enteric-coated tablets may be favourable in chronic antiinflammatory therapy.     

Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study.

In a double-blind, between-patient trial the efficacy and tolerability of two new non-steroid anti-inflammatory analgesics-diclofenac sodium (Voltaren) 50 mg b.i.d. and naproxen 250 mg b.i.d.-were compared in hospitalised patients with rheumatoid arthritis. Both drugs had a clearly positive effect on the duration of morning stiffness, bilateral grip strength, pain at rest, and pain on movement. No statistically significant difference between the two drugs was found with respect to clinical efficacy. Three patients treated with diclofenac sodium reported unwanted effects, as compared with seven patients receiving naproxen. These unwated effects led to premature discontinuation of the treatment in one patient on naproxen. Thus, although both drugs were well tolerated, it appeared that diclofenac sodium caused somewhat fewer unwanted effects.     

Oxaceprol is a Well-Tolerated Therapy for Osteoarthritis with Efficacy Equivalent to Diclofenac

The therapeutic equivalence and safety of treatment for 21 days with 400 mg t.i.d. oxaceprol (n= 132) and 50 mg t.i.d. diclofenac (n= 131) were assessed in a multicentre, randomised, double-blind study of a mixed population of patients with osteoarthritis of the knee and/or hip. In a per-protocol analysis of efficacy, the mean Lequesne index decreased by 2.5 points in the oxaceprol group (n= 109) and by 2.8 points in the diclofenac group (n= 109). The 95% confidence interval for the end-point difference revealed therapeutic equivalence. This was confirmed by assessments (visual analogue scale) of pain at rest, weight-bearing pain, pain on standing and pain on movement, all of which decreased to a similar extent under both treatments. The pain-free walking time increased in both groups from 10 min to 25 min by the end of the treatment period. Mobility was also increased to a similar extent by both drugs. The physicians assessed treatment as good or very good in 45–46% of patients in both groups. In all patients who received treatment, 28 and 37 adverse events were reported by 25 out of 132 (18.9%) and 33 out of 131 (25.2%) patients treated with oxaceprol and diclofenac, respectively. In 15 patients (11.4%) with 15 adverse events in the oxaceprol group and 25 patients (19.1%) with 27 adverse events in the diclofenac group, a relation to the medication was considered probable. The difference between the groups was statistically significant (p= 0.04106) for the number of these adverse events. Oxaceprol is therapeutically equivalent to diclofenac, but better tolerated than diclofenac in the treatment of osteoarthritis. Received: 15 February 1999 / Accepted: 7 September 1999     

Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis

Summary A multicentre randomised, double-blind, parallel group, general practice study was undertaken to investigate the efficacy and safety of aceclofenac (200 patients, 100mg twice daily and placebo once daily) in comparison with diclofenac (197 patients, 50mg three times daily) in patients with osteoarthritis of the knee. The treatment period of twelve weeks was preceded by a washout period of two weeks duration. At end point, patients in both aceclofenac and diclofenactreated groups exhibited significant improvement in pain intensity (p=0.0001). Although both treatment groups showed significant improvement in all investigators' clinical assessments (joint tenderness, swelling, pain on movement, functional capacity, overall assessment), there were no significant differences between the groups. There was, however, a trend towards greater improvement in complete knee movement and reduced pain on movement with aceclofenac. In patients with initial flexion deformity, aceclofenac was significantly more effective than diclofenac in improving knee flexion after 2–4 weeks of treatment. Patients' subjective assessment of pain relief demonstrated significantly greater efficacy with aceclofenac. At end point, 71% of patients in the aceclofenac group reported improvement in pain intensity as compared to 59% treated with diclofenac (p=0.005). Tolerability of aceclofenac was better than with diclofenac as fewer patients experienced gastrointestinal adverse events. In particular, the incidence of treatment related diarrhoea was less with aceclofenac (1%) than with diclofenac (6.6%). In summary, this study supports a therapeutic role for aceclofenac in arthritis and suggests that it is an alternative NSAID to diclofenac in the treatment of osteoarthritis.     

Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis.

OBJECTIVES--To compare the efficacy and gastroduodenal safety of a fixed-dose combination of diclofenac sodium 50 mg and misoprostol 200 micrograms twice daily with those of piroxicam 10 mg twice daily and naproxen 375 mg twice daily in patients with osteoarthritis. METHODS--A 4 week, randomised, double-blind, parallel-group, multicentre study was conducted in 643 patients with symptomatic osteoarthritis of the hip and/or knee, who required continuous non-steroidal anti-inflammatory drug therapy for 4 weeks and who were without significant upper gastrointestinal damage as confirmed by endoscopy. RESULTS--For patients who had pre- and post-treatment endoscopic examinations, gastroduodenal ulcers developed in 3 (1.5%) of 200 patients treated with diclofenac/misoprostol, 21 (10.3%) of 204 piroxicam-treated patients, and 17 (8.6%) of 198 patients receiving naproxen (Chi square = 13.771, p = 0.001). The improvement in the osteoarthritis severity index was greater in the diclofenac/misoprostol group than in the piroxicam group (p = 0.004). Changes in physician and patient global assessments showed no significant differences between treatment groups. The incidences of diarrhoea and abdominal pain were higher in the diclofenac/misoprostol group than in the piroxicam and naproxen groups. CONCLUSIONS--Diclofenac/misoprostol at twice daily dosing is associated with significantly fewer gastroduodenal ulcers than either piroxicam or naproxen. The efficacy of diclofenac/misoprostol in treating the signs and symptoms of osteoarthritis is at least comparable to that of piroxicam and naproxen.     

Celecoxib versus diclofenac in the management of osteoarthritis of the knee

OBJECTIVE: A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care. METHODS: Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial. RESULTS: Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib. CONCLUSION: Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.     

A double-blind comparison of the gastroduodenal safety and efficacy of diclofenac and a fixed dose combination of diclofenac and misoprostol in the treatment of rheumatoid arthritis.

This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.     

The long-term efficacy and tolerability of Voltaren (diclofenac sodium) and indomethacin in rheumatoid arthritis.

A report is given on a long-term controlled trial in which diclofenac sodium (Voltaren) was compared with indomethacin in 36 patients with rheumatoid arthritis, both drugs being administered in a dosage of 75-125 mg daily. In this trial, planned as a double-blind study, each patient was to participate for six months, after which the patients treated with diclofenac sodium were to be followed up for a further six months. By the end of the first six months, diclofenac sodium had proved to be clearly superior to indomethacin in terms of therapeutic efficacy. Moreover, unwanted effects referable to either the central nervous system or the gastro-intestinal tract were less common and less severe in the patient treated with diclofenac sodium than in those receiving indomethacin. These results demonstrate that, when given as long-term treatment to patients suffering from rheumatoid arthritis, Voltaren is both effective and well tolerated.     

A double-blind,multicentre, randomised clinical trial comparing the efficacy and tolerability of aceclofenac with diclofenac resinate in patients with acute low back pain

 The efficacy and tolerability of aceclofenac was compared with diclofenac resinate in a double-blind, multicentre randomised study in patients with acute low back pain suffering from degenerative spinal disorders. The study included 227 patients randomised to receive either aceclofenac 2 × 100 mg daily or diclofenac resinate 2 × 75 mg daily for up to 10 days. The primary objective was to demonstrate the clinical non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate, as assessed by changes from baseline in the visual analogue scale (0–100 mm) pain score, at rest and at visit 3 (final visit on day's 8–10). Secondary objectives included the time to early cure (resolution of pain) and global assessment of tolerability. Mean change in pain score at rest, and as visit 3, compared with baseline, was 61.6 mm (SD 24.5) for the aceclofenac group (n = 100) and 57.3 mm (SD 22.8) for the diclofenac resinate group (n = 105) in the per-protocol population. Similar changes were observed in the intention-to-treat population. Between-group differences of 4.5 mm and 5.5 mm for the per-protocol and intention-to-treat populations, respectively, demonstrated clinical non-inferiority of aceclofenac compared with diclofenac resinate. Furthermore, there was evidence for superiority of aceclofenac over diclofenac resinate in terms of statistical significance, as the one-sided 97.5% confidence interval was above −10 mm and 0 mm. In the intention-to treat population, a total of six aceclofenac-treated patients discontinued their medication owing to early cure, compared with only one patient receiving diclofenac resinate. Seventeen aceclofenac- (14.9%), and 18 diclofenac resinate-treated patients (15.9%) reported at least one adverse event. However, the total number of adverse events reported was lower in patients receiving aceclofenac (22 versus 31 in the diclofenac resinate group). In conclusion, non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate was demonstrated in patients with localised, uncomplicated acute lumbosacral pain. For the reduction in pain levels from baseline there was also evidence for superiority of aceclofenac compared with diclofenac resinate in terms of statistical significance, although this difference was not considered clinically relevant. The results also showed a trend towards a better safety and tolerability profile of aceclofenac over diclofenac resinate from a clinical point of view. Received: 28 June 2002 / Accepted: 12 December 2002     

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: a phase II, four-week, multicenter, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To compare the efficacy and tolerability of the novel cyclooxygenase 2-selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA). METHODS: Adults (n=583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting. RESULTS: All lumiracoxib doses were superior to placebo in relieving pain, improving stiffness, and improving physical function after 4 weeks. At study endpoint, pain relief was comparable among all lumiracoxib dosages and similar to diclofenac. Lumiracoxib tolerability was superior to diclofenac and comparable to placebo. CONCLUSION: Lumiracoxib provides predictable and sustained relief from pain, stiffness, and impaired physical function in OA. Lumiracoxib shows clinically comparable efficacy and superior tolerability to diclofenac.     

Pharmacokinetic studies on diclofenac sodium in young and old volunteers.

A singel 50 mg enteric-coated tablet of diclofenac sodium (Voltaren) was administered to two groups, each consisting of eight female subjects. The subjects in the one group were young adults all aged less than 22 years, while those in the other were all over the age of 62 years. The plasma concentration/time profiles, relative bio-availability, and urinary excretion pattern of the drug in the two groups were similar. Thus, in the absence of interacting factors, such as drugs and disease, the ability to absorb, metabolise, and excrete diclofenac sodium does not appear to be influenced by age.     

Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial

OBJECTIVE:. To compare the safety and efficacy of a topical diclofenac solution versus oral diclofenac in relieving the symptoms of primary osteoarthritis (OA) of the knee, in a randomized, double-blind, double-dummy equivalence trial. METHODS: A total of 622 men and women with radiological evidence of primary knee OA and mild to severe symptoms were randomly assigned to treatment with a topical diclofenac solution plus placebo oral capsules, or placebo topical solution plus oral diclofenac (50 mg) capsules. Patients applied 50 drops of study solution and took 1 study capsule 3 times daily for 12 weeks. Efficacy variables were pain and physical function, measured by the Western Ontario and McMaster Universities (WOMAC) VA 3.1 OA Index, and patient global assessment (PGA). Equivalence in the per-protocol group was based on previously defined ranges of clinically significant difference. Safety was assessed by evaluation of adverse events, vital signs, and laboratory data. RESULTS: The difference in mean (95% CI) change scores (final minus baseline) between treatments was 13.3 mm (-8.6 to 35.2) for pain (total scale 500 mm), 71.0 mm (-2.4 to 144.5) for physical function (total scale 1700 mm), and 4.3 mm (-1.2 to 9.8) for PGA (total scale 100 mm). The CI for each efficacy variable fell within the predefined equivalence ranges (pain, +/- 75 mm; physical function, +/- 255 mm; PGA, +/- 20 mm), indicating that no clinically relevant difference was found between the 2 treatment arms. Safety analyses of patients applying topical diclofenac solution revealed some minor skin irritation at the application site--mostly skin dryness in 83/311 (27%) patients--but a significantly reduced incidence, relative to oral diclofenac, of total and severe gastrointestinal (GI) adverse events, including dyspepsia, abdominal pain, diarrhea, and nausea. The number of patients developing abnormal liver function tests (including clinically significant elevation), hemoglobin, and creatinine clearance was significantly higher in the oral diclofenac group. CONCLUSION: Application of this topical diclofenac solution to the knee of patients with OA produced relief of symptoms equivalent to oral diclofenac, with minor local skin irritation, but significantly reduced incidence of diclofenac-related GI complaints and abnormal laboratory values.     

Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee

Aim: To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. Methods: This is a prospective, double‐blind, placebo‐controlled and intention‐to‐treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. Results: Of 84 patients screened, 74 patients formed the intent‐to‐treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry‐over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05). Conclusion: Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.     

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

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.     

Nabumetone Induces Less Gastrointestinal Mucosal Changes Than Diclofenac Retard

The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofenac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduodenoscopy. All patients exhibited significant improvement in pain severity and pain relief (p < 0.001 and p < 0.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p < 0.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side-effects.     

Gastric mucosal damage induced by nonsalicylate nonsteroidal antiinflammatory drugs in rats is mediated systemically

The gastric toxicities of an enteric-coated formulation and conventional indomethacin were compared in rats. Both formulations were equally damaging to the mucosa, suggesting that topical damage was not the major route of injury. The importance of systemically mediated damage was further determined by gastrotoxicity dose-response curves and pyloric ligation experiments in which indomethacin was administered either orally or parenterally, or into stomach or duodenum with the pylorus occluded. Gastric damage was significantly higher in those groups that had received the drug parenterally or intraduodenally. The extent of deeper mucosal damage, assessed histologically, was greater in parenterally dosed rats. In further experiments, oral and parenteral routes of administration of two other nonsalicylate NSAIDs, naproxen and sodium diclofenac, were found to be equally damaging to the mucosa. Our results show that indomethacin-induced gastric damage, unlike aspirin injury, is mediated mainly systemically. Enteric-coating may not be a useful strategy in reducing gastric injury by nonsalicylate, nonsteroidal antiinflammatory drugs.     

Efficacy and safety of diacerein in osteoarthritis of the knee: a randomized,multicenter, double‐dummy,diclofenac‐controlled trial in China

Aim: To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods: A total of 223 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 17‐week, randomized, double‐dummy, diclofenac‐controlled trial, with diacerein dosages of 100 mg/day and diclofenac sodium administered at 75 mg/day. Result: After 12 weeks of treatment, the total efficacy rates of patient/physician global assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2% respectively (P > 0.05). In the intent‐to‐treat population, the primary criterion (visual analogue scale [VAS] assessment of pain on walking 20 m) was significantly superior (P < 0.05) to baseline in both two groups. Significant improvement (P < 0.05) was also observed for the secondary criteria, which included tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short‐Form Health Survey (SF‐36). In the follow‐up period, there were no obvious changes in the above parameters in the diacerein group. However, in the diclofenac group, pain on walking 20 m, tenderness on palpation and WOMAC became worse after withdrawing the medications for 4 weeks. Moreover, the consumption of paracetamol was significantly lower in the diacerein group than in the diclofenac group during the follow‐up period. The incidence of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group (P > 0.05). Mild‐to‐moderate gastrointestinal disorders were the most frequent adverse events. Conclusion: Diacerein was shown to be as effective as diclofenac sodium in treating patients with knee OA, coupled with a carry‐over effect. Diacerein was generally well tolerated, with a good safety profile. No severe adverse events were occurred.     

A comparative short-term trial with Voltaren (diclofenac sodium) and naproxen in soft-tissue rheumatism.

In a double-blind study, diclofenac sodium (Voltaren)--administered for 14 days in a dosage of 25 mg t.i.d.--was compared with naproxen (250 mg b.i.d. for 14 days) in the treatment of 120 patients with soft-tissue rheumatism. Assessment of the efficacy of the two treatments was based upon changes, recorded once a week, in the following parameters: pain at rest and on movement, swelling, local tenderness, functional impairment, limitation of movement, and sleep disturbances. The incidence of unwanted effects was also recorded, and the effects themselves were classified according to the probability of their being causally related to the trial preparations. Both drugs appeared to be effective in relieving symptoms associated with soft-tissue rheumatism. In most indications the therapeutic efficacy of the two preparations was similar. In patients suffering from diseases affecting the shoulder region, however, diclofenac sodium was significantly more effective. Unwanted effects rarely occurred with either drug.