European journal of rheumatology and inflammation最新文献

It is postulated that the gastroduodenal mucosal side effects of naproxen are partly based on topical toxicity. With enteric coated aspirin tablets as a model product, enteric coated naproxen formulations have been developed. The extent of absorption is the same for enteric coated and plain tablets. The onset of absorption is delayed as a result of retention of larger particles in the stomach and more so when taken along with food. The gastric emptying of enteric coated naproxen granules is less influenced by food intake, but so far without any verified reduction of gastroscopic findings. The gastro-intestinal transmit has been studied by use of gamma scintigraphy.

The outcome of arthritis has several dimensions. These include mortality, morbidity, radiological measures of joint destruction, pain, and patients' satisfaction with therapy. Functional disability measured by health status questionnaires, is directly associated with long-term outcome and mortality. Long term clinical trials should incorporate functional indices as outcome measures. Studies measuring the outcome of arthritis should define clear end-points involving the determination of functional classes and this will allow standardised and sensitive end points. An example would be the time taken to reach a given functional class or increase from baseline by one functional class. Patients' satisfaction with treatment is a different dimension of response. There are considerable advantages in using an index of patients' satisfaction when determining the therapeutic efficacy in short term clinical trials. It gives a different indication of the response to treatment than conventional clinical and laboratory measures of disease activity. Alleviating pain and preservation of function remain the major therapeutic goals, and both reflect the outcome of arthritis. Outcome measures have shifted from laboratory markers and radiographic techniques to measures of health status, pain, and patients' satisfaction. These should become a routine part of patient assessment.

The aim of this 8 week study, was to compare the tolerability and efficacy of enteric-coated (ECT) and plain naproxen tablets (PT). Ninety eight patients (mean age 66 years) with osteoarthritis were included in a randomized, multi-centre, double-blind, cross-over study. Response variables were monitored at 2 week intervals for the duration of the study. Sixteen patients withdrew from the study, eight because of gastrointestinal (GI) adverse events (ECT 5, PT3). There was no significant difference in patients preference. Eighteen patients reported GI adverse events only on PT compared to 9 on ECT (n.s.). In the first treatment period the severity of adverse events was significantly less on ECT (P = 0.015). Both enteric-coated and plain naproxen tablets were effective and well tolerated. In conclusion, the study did not show any clinical significant difference in tolerability or efficacy between the formulations in osteoarthritis of the knee and/or the hip, although some of the variables did show statistical significant difference or tendency in favour of the enteric coated tablets.

Various methods are available for investigating gastrointestinal adverse effects of NSAIDs. Upper endoscopy is regarded a gold standard for controlled studies, but the grading and categorization of the visual impression of mucosal changes is complicated. Faecal blood loss represents another aspect of the toxicity, but quantitative measurements require the cumbersome procedure of 51Cr-labelling of red blood cells. For monitoring distal gut effects, permeability tests can be applied, and combination of tracer substances may further enhance the method. Measurements of electrical potential differences over the gastric mucosa are also available to monitor functional aspects of the gastric mucosal integrity. Controlled endoscopic trials have indicated an advantage of enteric coated naproxen tablets over plain tablets. Distal transfer of the toxicity by small bowel release of the active substance, has not been confirmed by permeability tests.

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.

Thirty-nine patients with ankylosing spondylitis participated in a randomized, double-blind, double-dummy, multi-cross-over study with enteric-coated (ECT) and plain (PT) naproxen tablets. The duration of the study was 24 days with 6 treatment periods of 4 days. The majority of the patients were taking 750 mg naproxen daily. The mean plasma concentration of naproxen in the morning was 36% higher with ECT (p < 0.001). No significant differences regarding duration of morning stiffness and night time pain were found in this patient category. The mean duration of morning stiffness was 116 minutes (ECT) and 125 minutes (PT). We were not able to show correlation between plasma concentration of naproxen and duration of morning stiffness.

Two naproxen formulations were compared with regard to gastroduodenal endoscopic findings. Using a dose of 500 mg bid for one week, plain tablets were compared to enteric coated granules in a gelatine capsule in a randomized, cross over, double-blind, double dummy study in 16 healthy, male volunteers. Endoscopic evaluation revealed no difference between the two formulations. Since previous studies with enteric coated naproxen tablets indicated a favourable side effect profile compared to plain tablets, the present data indicates that enteric coated formulations are not all alike, and should be studied individually.

One hundred patients with rheumatoid arthritis were entered into a randomised, double-blind, cross-over study of naproxen (500 mg b.d.) and diclofenac (50 mg t.i.d.). Each treatment period lasted four weeks with a wash-out period of up to one week on admission and again between periods of active therapy. Compared with baseline, both treatments significantly reduced the duration of morning stiffness, Ritchie Articular Index, daytime and night-time pain and produced a significant improvement in the disease status. Forty-two non-serious presumed side-effects were reported in 21 patients (21%). All were characterised by common everyday signs and symptoms. These largely related to the upper gastrointestinal tract and typical of those commonly reported for non-steroidal anti-inflammatory agents. There were no statistically significant differences between the two treatments for any of the efficacy parameters or in the incidence of side-effects. Patients also expressed an equal preference for the two drugs.