V. Wright

CAPTOPRIL: A NEW TREATMENT FOR RHEUMATOID ARTHRITIS?

Captopril, an inhibitor of angiotensin converting enzyme, is prescribed for hypertension. Its molecular structure shares features with D-penicillamine, in that both agents contain a thiol group. In addition, captopril has immunosuppressant activity. Captopril was therefore considered a potential slow-acting drug for treating rheumatoid arthritis. In an open study 15 patients with active arthritis were treated with captopril and followed for 48 weeks. Two-thirds of the patients reported improved arthritis symptoms, and significant changes were seen in several clinical and biochemical measurements, notably Ritchie articular index, clinical score, plasma viscosity, and C-reactive protein. Side-effects were generally mild and included transient taste loss, rashes, and hypotension. Only 2 patients withdrew as a result of drug intolerance.

Comparison of three physiotherapy regimens for hands with rheumatoid arthritis.

Etude sur 30 malades pendant 3 semaines. Les ultrasons et les bains faradiques ne semblent pas presenter davantages par rapport aux exercices conventionnels avec traitement par la cire fondue. Le traitement conventionnel est moins couteux

A double-blind, parallel study of tenoxicam and piroxicam in patients with osteoarthrosis

A double-blind, parallel group study was carried out in 30 patients with osteoarthrosis to compare the efficacy and tolerance of tenoxicam (40 mg/day) and piroxicam (40 mg/day) given over a period of 4 weeks. All had previously been treated with a variety of non-steroidal anti-inflammatory agents and/or analgesics. Patients were allocated at random to one or other treatment group. Clinical and laboratory assessments were made on entry and after 2 and 4 weeks of treatment. The results showed that both drugs improved general pain, the improvement being somewhat greater with tenoxicam. Little change was noted in other symptoms with either treatment. Side-effects reported were mainly gastro-intestinal. Six of the 15 piroxicam-treated patients stopped treatment because of adverse reactions, 1 because of treatment failure and 1 because he preferred previous treatment. Three of the 15 tenoxicam-treated patients discontinued because of adverse reactions. The remaining patients (7 on piroxicam and 12 on tenoxicam) elected at the end of the trial period to remain on their respective treatment instead of their previous medication.

A single-blind comparative study of auranofin and hydroxychloroquine in patients with rheumatoid arthritis

SummaryForty patients with rheumatoid arthritis were randomly allocated to treatment with auranofin 3 mgb.d. or hydroxychloroquine 200 mg b.d. Twenty patients received each drug. Efficacy was analysed by comparing patients with available data at weeks 12, 24, 36 and 48 with baseline within each treatment group, and between treatment groups at each of these same time points. There were statistically significant improvements in all measured parameters of clinical efficacy among hydroxychloroquine treated patients, and in all efficacy parameters except one (time to onset of fatigue) in the auranofin treatment group. There were no significant differences between the treatment groups for any parameter of clinical efficacy. Of the laboratory parameters measured, only auranofin treatment produced statistically significant decreases in the concentration of IgA, IgG and IgM, with significant differences between treatments being detected in the case of IgA and IgG. Eight auranofin-treated and three hydroxychloroquine-treated patients were withdrawn because of adverse reactions before completing 48 weeks treatment. The commonest reason for stopping auranofin treatment was diarrhoea (5 cases). Three hydroxycloroquine-treated and two auranofin-treated patients were withdrawn from the study because of inefficacy of the trial drug. Auranofin had a more ’potent’ biochemical profile than hydroxychloroquine, although more patients tolerated one year of treatment with the latter drug.

A clinical and biochemical assessment of etidronate disodium in patients with active rheumatoid arthritis

SummaryDiphosphonates reduce the rate of bone turnover. They have additional pharmacological properties improving adjuvant arthritis in rats and lowering ESR in this condition. We have evaluated etidronate disodium, a diphosphonate commonly prescribed in the United Kingdom for Pagets disease in patients with rheumatoid arthritis. Apart from an early improvement in articular index, perhaps reflecting anti-inflammatory activity, no significant change occurred in clinical variables or in laboratory indices of ‘secondline’ action at a dose of 5 mg/kg/day.

A comparison of faecal blood loss caused by tenoxicam and piroxicam in normal healthy male volunteers

Faecal blood loss arising from tenoxicam at a dose of 20 mg/day was compared to that arising from piroxicam at a dose of 20 mg/day in a double-blind, parallel comparative study in 12 healthy male volunteers. Faecal blood loss was measured for a 1-week run-in on placebo, during 4 weeks of treatment and for a 2-week post-treatment period in both groups. Plasma levels for tenoxicam and piroxicam confirmed good compliance in all subjects. Mean blood loss during the placebo run-in period was 0.35 ml/day. Mean blood loss during treatment with tenoxicam was 0.84 ml/day and with piroxicam 0.81 ml/day. There was no significant difference between these measurements. On cessation of treatment, faecal blood loss continued both in the tenoxicam group (mean 1.30 ml/day) and piroxicam group (mean 1.41 ml/day). The difference between these was not statistically significant. No significant haematological or biochemical abnormality resulted from either of the two trial drugs during the period of the study. Urinalysis and NAG/creatinine ratio also remained unaltered in both treatment groups.

A comparison of prednisolone with azathioprine and prednisolone with intramuscular gold in rheumatoid arthritis.

SummaryPulse prednisolone hemisuccinate therapy (500 mg given intravenously on three occasions over two weeks) has been combined with either intramuscular sodium aurothiomalate or azathioprine in an assessment of 30 patients with rheumatoid arthritis. Significant improvement in a variety of clinical and biochemical assessments was seen in both groups. Both treatments were well tolerated by the patients and prednisolone appeared to accelerate the response to sodium aurothiomalate and azathioprine but there was no great evidence that it enhanced it.

Comparison of 12 different containers for dispensing anti-inflammatory drugs.

Twelve containers manufactured by 10 pharmaceutical companies for dispensing anti-inflammatory drugs, 10 of which are currently in use in the United Kingdom, have been compared in 99 patients with arthritis of the hands. Patients were given the containers in random order and were asked to open them, extract the tablets, and close them. Patients were questioned on ease of handling at each stage and were then timed on reopening and closing each container. Finally, the patients were asked which container was the best and which was the worst. There was a wide variation in popularity of containers. One was judged outstanding on almost every attribute, and four were preferred over the others on most attributes. A successful container for arthritic hands is likely to have a sharply angulated or wing cap placed on a tall slim base that is also angulated. Flip off tops, tops with long threads requiring many turns, very small containers, and glass were regarded as unfavourable. Manufacturers should take note of these findings and, where necessary, consider redesigning the containers.

An assessment of faecal blood loss from Ro 21-5521, a novel non-steroidal anti-inflammatory agent, in normal volunteers

Faecal blood loss arising from Ro 21-5521, a novel non-steroidal anti-inflammatory agent with a long plasma half-life of about 41 hours, was evaluated in a double-blind crossover study against matched placebo in 12 volunteers. After a 1-week run-in period to determine baseline values, subjects were allocated at random to receive either 250 mg Ro 21-5521 per day or placebo for 2 weeks before being crossed over to the alternative treatment for 2 weeks. They were then followed-up for a further 2 weeks. Blood loss was calculated from 51Chromium tagged red blood cells in stools collected for a 96-hour period during each week of the study. Plasma levels of Ro 21-5521 were also measured twice weekly throughout the study. The results showed that with a drug of this long half-life, faecal blood loss may continue for at least 4 weeks after cessation of trial therapy of 2 weeks. It is recommended that in the evaluation of faecal blood loss resulting from drugs with a long half-life, a parallel group study, each group receiving only one drug (or one drug crossed against placebo), is the study design of choice.

A comparison of therapies which may influence trace metals in rheumatoid arthritis.

SummaryForty-five patients with active rheumatoid arthritis (RA) were treated with D-Penicillamine (DPA), zinc sulphate or trien for 24 weeks. Clinical and biochemical assessments were made on eight occasions during the treatment period. Results supported the view that DPA is efficacious causing both clinical and biochemical improvement, whereas zinc sulphate provided clinical benefit in some patients without improving the biochemistry, and trien was ineffective in both respects. The results indicate the need for more thorough investigations of the effect of drugs on trace metal distribution in RA.