Cervical myelopathy complicating multiple joint replacement in rheumatoid disease.

The incidence of cervical myelopathy and subluxation was investigated in 48 patients with rheumatoid disease who had three or more major lower limb joint replacements. Eight (17%) developed cervical myelopathy requiring cervical fusion. This was the subsequent cause of death in two. Four further patients demonstrated clinical features of myelopathy. Cervical subluxation was present in 29 of 44 (66%) in whom adequate radiographs were available. The development of cervical symptoms and signs could not have been predicted from the sex, age of onset, duration of disease or steroid therapy. Radiographic changes in the cervical spine were independent of major lower limb joint destruction and were often not present when planning a programme of joint replacement. Fifty-one control patients were studied. Cervical myelopathy occurred in 2 (4%) and subluxation in 24 (47%). The development of rheumatoid changes in the cervical spine was unrelated to involvement of the hip or knee joints in the control group. There was a significant (p less than 0.05) increase in the incidence of cervical myelopathy in patients with multiple lower limb joint replacements compared with the control population.

Double-blind multicentre UK hospital studies of isoxicam vs naproxen.

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled comparison of tiaprofenic acid and ibuprofen in osteoarthritis.

A multicentre double-blind crossover study of tiaprofenic acid (600 mg daily) against ibuprofen (1.2 g daily) was undertaken in 77 patients with osteoarthritis to compare their efficacy and tolerance. No difference was found between the two agents, both giving pain relief and being safe and acceptable to the majority of patients. It is concluded that in this short-term study, both agents offer effective and safe treatment for osteoarthritis.

Benoxaprofen: side-effect profile in 300 patients.

Out of 300 patients who had taken benoxaprofen for a mean of 6.4 months, 196 (65.3%) reported side effects, resulting in 104 patients (34.6%) having the drug withdrawn. Out of 42 patients aged over 70, 35 (83.3%) had side effects and 29 (69.0%) had the drug withdrawn because of them. cutaneous side effects accounted for 180 (69.5%) of all 259 side effects reported. The commonest cutaneous side effect was photosensitivity, which occurred in 86 patients (28.6%). Photosensitivity, which occurred in half of the patients treated in the summer, resulted in withdrawal of benoxaprofen in 26 (30.2%) of the patients who experienced it. Onycholysis was observed in 38 patients (12.6%) and was frequently unnoticed by patients. The overall incidence of gastric side effects was 12.6% (38 patients), and the figure rose to 40.5% (17 cases) in patients over 70. During treatment with benoxaprofen one patient developed an active duodenal ulcer but no cases of major gastrointestinal haemorrhage occurred. Multiple subepidermal cysts (milia) were observed in 16 patients, who had been treated for a mean of 10.8 months. These findings show that benoxaprofen is a potent phototoxic drug and that the manufacturers' recommended dosage of 600 mg daily is associated with an unacceptable incidence of side effects in the elderly.

Diclofenac sodium (Voltarol): a double-blind comparative study with ibuprofen in patients with rheumatoid arthritis.

A double-blind comparative trial in 60 patients, using diclofenac (Voltarol) and ibuprofen (Brufen), showed a considerable improvement in morning stiffness amongst females in the diclofenac group. However, no significant differences was noted between these two drugs in relation to pain score, articular index or proximal interphalangeal joint size. Analysis of withdrawals and side-effects suggests that while ibuprofen may be slightly better tolerated, it is also associated with significantly more withdrawals due to lack of effect. No significant change in laboratory studies was noted, except for a slight decrease in mean haemoglobin levels. The trialist noted that all of the drop-outs and side-effects reported came from one hospital out of the four participating; this was possibly due to differences in pre-trial drug therapy and to the hospital being in an urban, rather a rural, situation.

Serum concentrations of flurbiprofen in rheumatoid patients receiving flurbiprofen over long periods of time.

Serum concentrations of flurbiprofen were measured following single oral doses of 50 mg to 200 mg in patients who previously had received flurbiprofen over long periods of time. The apparent elimination half-lives in groups of patients who received different doses were not significantly different from each other nor from the value previously obtained in a group of healthy volunteers given a single oral dose of 50 mg. Areas under serum concentration versus time curves were linearly related to dose over the range of doses examined. The results indicate that the pharmacokinetics of flurbiprofen are not significantly dose-dependent over the range of doses studied and that administration of relatively high doses of flurbiprofen over long periods of time neither induces nor inhibits flurbiprofen metabolism.

A double-blind crossover comparison of tolmetin sodium and phenylbutazone in the treatment of rheumatoid arthritis.

A double-blind crossover study was carried out in 24 patients with rheumatoid arthritis to investigate the relative efficacy of tolmetin (1600 mg/day) and phenylbutazone (400 mg/day). Each drug was given for 4 weeks, preceded by a 2-week wash-out period during which patients received paracetamol alone for pain relief. Assessments were made of duration of morning stiffiness, grip strength, articular index, joint size, and degree of pain. Both drugs produced significant improvements compared to paracetamol, particularly in pain relief and, apart from morning stiffness, tolmetin proved equally effective as phenylbutazone. Three patients (2 on tolmetin and 1 on phenylbutazone) were withdrawn because of side-effects. In general, however, both drugs gave rise to only minor side-effects.

Double-blind cross-over study of ketoprofen and phenylbutazone in patients with chronic osteoarthrosis of the hip.

A double-blind cross-over study of oral ketoprofen capsules 100 mg/day and phenylbutazone capsules 400 mg/day has been carried out in 44 patients with osteoarthrosis of the hip. All patients received each drug for 4 weeks. Eight patients were withdrawn for various reasons during the trial period, leaving 36 assessable patients (20 males and 16 females), whose ages ranged from 31-88 years (mean 66 years). In this series of patients the results suggest that there is little to choose in efficacy between the two drugs at these dosages. All patients showed improvement after 4 weeks' treatment on either drug and of 12 parameters measured only two showed a statistically significant favour to phenylbutazone (intermalleolar straddle and intercondylar distance; both when pain first appeared). Side-effects were reported equally with both medications, even though of necessity the protocol called for the exclusion of patients with previous intolerance or sensitivity to phenylbutazone. The study was instituted during the early evaluation of ketoprofen when the dosage of 100 mg/day was being tried; it is felt that a more significant result may possibly have emerged if the dosage had been the now recommended one of 150 mg/day.