1 Seventeen patients with rheumatoid arthritis were studied in a double‐ blind crossover trial contrasting three different times of administration of twice‐daily flurbiprofen. 2 Twelve of these patients were also studied when taking the same dose of flurbiprofen as a split dose four times a day. 3 Symptoms and signs of the disease were self‐ assessed throughout the day for several days on each regimen and the information was analysed for rhythmicity. 4 Twice a day flurbiprofen may be more effective than four times daily flurbiprofen, and the regimen without an evening dose was the least effective of three twice‐ daily treatments tested. 5 Circadian rhythms of grip strength and finger joint size were demonstrated, and were similar on all treatment regimens. 6 These rhythms have a similar pattern to those detected during studies of immune responses, and it is suggested that morning stiffness in rheumatoid arthritis is not only the result of nocturnal inactivity, and may respond to appropriately timed medication given to decrease inflammation or to suppress other aspects of the immune response.
SUMMARY Symptoms and signs of rheumatoid arthritis vary within the day and from day to day. Interesting and possibly important observations can be missed when evaluations are based only on outpatient measurements, which are likely to be made at only one time and at infrequent intervals. We have found that patients can measure their own grip strength and finger joint sizes at home, and simultaneously assess overall pain and stiffness on numerical scales. Measurements made by patients were reproducible when made at the same time of day if on the same treatment. The patient's subjective assessment of pain and stiffness is a useful measure of the severity of rheumatoid arthritis. These pain and stiffness ratings were found to be well correlated with the patient's objective measurements of finger joint size and grip strength. Information not otherwise available can be collected by studying patients at home with these self-measurement techniques. These have allowed the demonstration of circadian variations in the signs and symptoms of rheumatoid arthritis and improved the evaluation of drugs studied in clinical trials.
SUMMARY Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5 6 mg daily, at either 0800 h, 1300 h, or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 1 1-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised.
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