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NIJMEGEN, The Netherlands, May 29 -- For the acute pain of monoarticular gout over four days, it's a tossup between oral prednisolone and naproxen (Aleve), a randomized trial found.

In an equivalence study, pain scores for the corticosteroid and NSAID were similar as were the number of adverse events, which were minor, Hein Janssens, M.D., of Radboud University Nijmegen Medical Center here, and colleagues reported in the May 31 issue of The Lancet.

Yet for gastrointestinal-bleeding reasons, the authors said, the study provides a strong argument to consider prednisolone as a first treatment option over NSAIDs for patients with gout

The conventional drugs for gout arthritis are colchicine and NSAIDs. Use of cochicine has declined because of its disadvantage in renal failure and NSAIDS have been associated with gastrointestinal and cardiovascular risks often seen in gout patients.

About 40% of upper-GI bleeding events are attributable to NSAIDs, while the drugs' cardiovascular risks prompted the American Heart Association recently to recommend restricted use, the researchers wrote.

Prednisolone may also turn out to be less costly because they don't require gastroprotective drugs added to treatment with NSAIDs, the researchers said.

The researchers undertook a randomized clinical trial to test the equivalence of naproxen and prednisolone for treating monoarticular gout. From March 24, 2004 through July 14, 2006, family physicians in the eastern part of Holland were asked to send all patients with monoarthritis to the trial center, even if gout was not the most likely diagnosis.

The study eventually included 120 primary-care patients (mean age 57; 89% men) with gout confirmed by presence of monosodium urate crystals. Of the patients, 53% had hypertension and 19% cardiovascular disease.

Sixty patients were randomly assigned to prednisolone

(35 mg once a day) and 60 to naproxen (500 mg twice a day) for five days. Treatment was masked for both patients and physicians.

The primary outcome was pain measured on a 100-mm visual analog scale while the a priori margin for equivalence was set at 10%.

Data were incomplete for one patient in each treatment group, so analyses included 59 patients in each group.

After 90 hours, the reduction in the pain score was 44.7 mm and 46.0 mm for prednisolone and naproxen, respectively (difference 1.3 mm; 95% CI -9.8 to 7.1), suggesting equivalence.

The difference in the size of change in the pain score for the whole observation period (944 intervals) was 1.57 mm (CI -8.65 to 11.78).

Reductions in the pain scores were equivalent and went from 62 mm to 17 mm for prednisolone and 59 mm to 13 mm for naproxen, in a similar pattern.

For general disability, the differences were 0.93 mm (-9.51 to 11.7), and for walking disability, 0.72 mm (-11.3 to 12.37). In all cases these differences non-significantly favored naproxen, the investigators said.

Adverse effects were similar and minor between groups, and resolved by the three-week follow-up. No adverse effects were reported for 66% of the prednisolone patients and 63% of those taking naproxen (P=0.42).

After three weeks, all patients reported, by telephone, complete relief of signs and symptoms, and no patients reported a recurrent attack.

Study limitations included assessment of complete relief based on self-reporting, the use of non-validated scales to assess disability outcomes, and a study population limited to white Dutch people.

Although no patients were excluded in this study because of the risks from prednisolone treatment, a quarter of originally eligible patients had to be excluded because of direct safety risks had they been treated with naproxen. For these patients, a five-day treatment with prednisolone would have been no problem, the researchers said.

In addition to better safety, they wrote, the direct drug costs would also be less if systemic corticosteroids, such as prednisolone, were the first-line drug choice. Furthermore, the additional costs of gastroprotective drugs added to NSAIDs should be considered.

In an accompanying comment, Timothy H. Rainer, M.D., and Colin Graham, M.P.H.., of Chinese University of Hong Kong pronounced the study a "significant step forward for gout" and discussed the two main hindrances to implementing these findings in clinical practice.

First, they said, although well-designed, the study was fairly small and was done at one center. It needs to be repeated in other locales with different rates of gastrointestinal disease.

Second, they said, changes in clinical practice often need strong marketing forces, which might not occur unless drug companies stand to benefit from newer more expensive drugs.

Nevertheless, they concluded, this trial "will go some way to satisfy both rheumatological purists and front-line pragmatists that short-term oral corticosteroids are as equally effective as NSAIDs in the initial treatment of acute gout and gout-like syndrome."

The researchers and the editorial writers declared no conflict of interest. This study was funded by the Rheumatology Research Fund Arnhem, The Netherlands. The employees of the Pharmacy Riet (Rotterdam) and the drug dispensing Primary Care Center Lobede (Lobith-Tolkamer) prepared the study drugs.

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