ArticlesUse of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial
Introduction
Gout is a painful inflammatory arthritis with a sudden onset and tendency to recur.1 The gold standard for the diagnosis of gout is the microscopic identification of monosodium urate crystals in synovial fluid or tophi. Acute severe pain prompts most patients to seek medical care immediately.
The history of gout is marked by famous patients, including Desiderius Erasmus, Holy Roman Emperor Charles V and Immanuel Kant; by impressive scientific researchers like Antoni van Leeuwenhoek, who first identified monosodium urate crystals from a tophus with his hand-held microscope in the 1600s, Anton Von Störck, who laid the foundations for the modern use of colchicine in the 1800s, and Sir Alfred Baring Garrod, who first postulated in the 1900s that deposits of serum urate were the cause not the consequence of gout; by various prescientific treatments, such as diets, plasters, baths, herbal remedies, opium; and by many disputes about the triggering factors, including socioeconomic status, alcohol, food, and drugs.2, 3, 4, 5, 6, 7 Gout has a substantial effect on the population. An estimated 1–2% of adults in developed countries have the disorder,4, 8 which creates a substantial burden of work-related and medical costs.9
The most widely used drugs for gout arthritis are colchicine and non-steroidal anti-inflammatory drugs (NSAIDs). Colchicine is the most longstanding treatment, but its use has declined because of its narrow therapeutic window,10, 11 its disadvantage in the case of renal failure,12 and the availability of NSAIDs. The first choice of drug treatment is now NSAIDs,13, 14 despite their gastrointestinal15, 16 and cardiovascular risks.17 About 40% of upper gastrointestinal bleeding events are attributable to NSAIDs (risk is highest during the first week of use),16, 18 and the cardiovascular risks prompted the American Heart Association recently to recommend restricted use.19 Loss of renal function, fluid retention, and interaction with anticoagulants, further discourage the use of NSAIDs. The drawbacks of the NSAIDs are especially important in the case of gout,13 because patients are at high risk for the gastrointestinal side-effects, most of them are middle aged or elderly,20, 21 and many have comorbid renal and cardiovascular diseases.6, 12, 21, 22, 23
As a consequence, safer therapeutic approaches are needed.14 Systemic corticosteroids might be a safe alternative, particularly in elderly people.13, 14, 21 Although they are associated with side-effects such as osteoporosis, fluid retention, and hyperglycaemia when used long term, systemic corticosteroids do not have important drawbacks in the short term.24, 25 However, the only evidence on the effectiveness of systemic corticosteroids in the treatment of gout is from three studies included in a recent systematic Cochrane review:26 two small, unblinded, non-randomised studies,27, 28 and another in patients with gout-like arthritis not confirmed with tests for monosodium urate crystals.29
We aimed to investigate whether oral prednisolone is equivalent to naproxen in patients with confirmed gout arthritis.
Section snippets
Patients
We designed a randomised, double-blind, active-comparator, controlled trial to test for equivalence of prednisolone and naproxen for the treatment of gout arthritis.
The study took place in the eastern part of the Netherlands in a population of about 330 000 inhabitants. In the Netherlands, patients are listed with a personal family doctor who provides primary care for about 2250 people and refers patients for secondary medical care if needed.
From March 24, 2004, until July 14, 2006, family
Results
93 family doctors sent 381 patients with suspected monoarthritis to the trial centre. Of these 216 (57%) met the inclusion criterion of gout after identification of monosodium urate crystals (figure 1). 96 (32%) were excluded for several reasons. Excluded patients were older (mean age 60·5 years, SD 12·8) than patients who underwent randomisation (57·5, 12·7). 120 completed the trial. Two patients, one in each treatment group, recorded their visual analogue scale in an inappropriate way so were
Discussion
Both oral prednisolone 35 mg once a day and naproxen 500 mg twice a day seemed effective in the treatment of gout arthritis. The 95% CI for the small and non-significant, difference between the two treatments in pain reduction after 90 h (−9·8 to 7·1) was within the predefined 10% margin of equivalence. The 95% CI of the difference in the size of change in pain during 90 h (−8·65 to 11·78 mm) was outside our a priori margin but was within the 13% margin used as the non-negligible difference in
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2021, The LancetCitation Excerpt :Early administration of anti-inflammatory treatment (table 1) is recommended to rapidly suppress joint pain and inflammation. Head-to-head clinical trials comparing oral agents with different mechanisms of action have shown equivalent efficacy between oral prednisolone, non-steroidal anti-inflammatory drugs (non-selective or COX-2-selective), and low-dose colchicine for gout flare management.91–94 These studies have indicated that oral corticosteroids might have a slightly better safety profile than non-steroidal anti-inflammatory drugs,92,93 and that fewer side-effects are caused by non-steroidal anti-inflammatory drugs than by low-dose colchicine.91