A six-month double-blind trial to compare the efficacy and safety of meloxicam 7.5 mg daily and naproxen 750 mg daily in patients with rheumatoid arthritis.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.

Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations.

Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.

Thymopentin (TP-5) in the treatment of rheumatoid arthritis.

A randomized control trial of TP-5 in rheumatoid arthritis is reported. In a multicentre study, 76 patients were treated with TP-5 50 mg or placebo three times a week for 3 weeks as a slow intravenous injection, and followed for 7 weeks. Clinical parameters such as the Ritchie index and sum score of swollen joints improved significantly on TP-5 compared to placebo. Laboratory parameters did not change but an increased skin test score to common recall antigens was observed. Toxicity was minimal. TP-5 is a potentially useful agent in the treatment of rheumatoid arthritis, although further studies are required to determine the optimal treatment regimen.

Arthritis and coeliac disease.

We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type A1, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing spondylitis was identified, though in a control group of 100 patients with Crohn's disease the expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p less than 0.01). Arthritis appears to be a rare manifestation of coeliac disease. This relationship may provide important clues to the role of gastrointestinal antigens in rheumatic diseases.

Treatment of sleep disturbance in arthritis with chlormezanone.

A double-blind, crossover study was carried out in 31 patients with rheumatoid arthritis or osteoarthritis who suffered from insomnia which was considered to be caused primarily by their disease. Patients received 7-day courses of 400 mg chlormezanone, 200 mg chlormezanone and placebo in a pre-determined random order. Patients rated chlormezanone significantly (p less than 0.025) more effective than placebo in overcoming sleep disturbance and preferred the 400 mg dose. There was also a trend towards better quality of sleep with chlormezanone, although this did not attain statistical significance in this relatively small study. Daytime alertness was similar for both active and placebo treatment periods. Chlormezanone, therefore, would seem to be a useful addition to antirheumatic therapy when there is related insomnia.

Short-term efficacy and tolerance of tiaprofenic acid ('Surgam') in rheumatoid arthritis and osteoarthritis: multi-centre, placebo-controlled trials.

Two multi-centre, placebo-controlled, crossover trials of tiaprofenic acid were conducted to an identical design: one in 80 patients suffering from rheumatoid arthritis, the other in 60 patients suffering from osteoarthritis. After a washout period, each patient received 600 mg tiaprofenic acid daily and placebo each for 1 week. The results were similar for both trials. Tiaprofenic acid was more effective than placebo in both rheumatoid arthritis and osteoarthritis and differences in all the assessments of efficacy used were statistically significant. This significance was attained from the first day in rheumatoid arthritis and from the second day in osteoarthritis. Tiaprofenic acid was as well tolerated as placebo. Routine laboratory tests revealed no adverse effects. Possible side-effects, which were predominantly mild and related to the gastro-intestinal system, were reported by 23% patients with tiaprofenic acid and 21% patients with placebo. The 2 patients withdrawn for possible side-effects were both receiving placebo.

Clotrimazole in rheumatoid arthritis.

Forty-seven patients with active rheumatoid arthritis took part in an 8-week controlled study in which clotrimazole was compared with a standard nonsteroidal anti-inflammatory agent, ketoprofen. Although clotrimazole was shown to be effective in the treatment of the disease and superior to ketoprofen in certain measurements, if was also responsible for a high incidence of adverse effects. Improvement with clotrimazole took place more slowly but was more sustained than with ketoprofen. A significant rise in plasma cortisol and a fall in white cell count was observed in the clotrimazole treated patients.

Clinical experience with tolmetin sodium.

Two studies are reported with tolmetin sodium. The first compared tolmetin sodium, phenylbutazone and placebo in rheumatoid arthritis. The second compared tolmetin sodium and aloxiprin in osteoarthritis and soft tissue rheumatism. In the first study, a double-blind crossover trial involving 12 patients, tolmetin sodium (1600 mg daily) was shown to be superior to placebo and comparable to phenylbutazone (400 mg daily). The reductions in morning stiffness and pain were statistically significant when compared to placebo. Tolmetin sodium and aloxiprin were compared in the treatment of osteoarthritis in a single-blind study which investigated efficacy and safety over a 3-month period. Initial dosages were 1600 mg tolmetin sodium and 6 g aloxiprin (equivalent to 5 g aspirin) daily. Thirty-four patients were enrolled in the study. Both drugs produced an improvement over the 3-months treatment period. The reduction in pain was statistically significant. The dosage of tolmetin sodium remained at 1600 mg daily for the 3-month duration of the study but side-effects necessitated the reduction of the dosage of aloxiprin in many patients and after 3-months' treatment the mean dosage was 4 g daily. Five patients withdrew from the tolmetin sodium group and 11 from the aloxiprin group. Adverse reactions including limiting side-effects, were about twice as common with aloxiprin compared to tolmetin sodium.

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.

Temporo-mandibular joint disease in ankylosing spondylitis.

The occurrence of temporo-mandibular joint (TMJ) disease in ankylosing spondylitis is not widely recognized and its incidence is disputed. Seventy-nine patients attending two routine rheumatology clinics were therefore examined by dental surgeon and nine (11-5 per cent) were considered to have specific TMJ involvement. These patients were older than the remainder, and had more extensive spinal and peripheral joint disease. Symptoms were mild and the predominant clinical feature was restricted mouth opening, which could present considerable difficulties during emergency anaesthesia. Bilateral condylectomy was undertaken in one patient with some benefit.

Measurement of side effects of drugs.

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin-tinnitus, deafness, and gastrointestinal disturbance-were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used.

Fenoprofen in treatment of osteoarthrosis of hip and knee.

Two studies on 41 patients with osteoarthrosis of the hip or knee have shown fenoprofen-a compound with analgesic and anti-inflammatory properties-to be an effective addition to the drug treatment of these conditions. It was found to be superior to paracetamol but no statistically significant difference was shown in a comparison with phenylbutazone.