Naproxen, Prednisolone May Be Effective First-Line Treatment of Gout CME

News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Disclosures

Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians; Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians

June 2, 2008 — Gout is treated effectively with naproxen or oral prednisolone as a first-line treatment, according to the results of a double-blind, randomized controlled trial reported in the May 31 issue of The Lancet.

"Non-steroidal anti-inflammatory drugs [NSAIDs] and colchicine used to treat gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects," write Hein J.E.M. Janssens, MD, from the Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands, and colleagues. "Systemic corticosteroids might be a beneficial alternative. We investigated equivalence of naproxen and prednisolone in primary care."

With use of computer-generated randomization, 120 primary-care patients with monoarticular gout confirmed by the presence of monosodium urate crystals were randomized to receive either prednisolone (35 mg once a day; n = 60) or naproxen (500 mg twice a day; n = 60), for 5 days. Both patients and clinicians were blinded to treatment assignment, and analyses were per protocol and by intent-to-treat. The main endpoint was pain intensity measured on a 100-mm visual analog scale, with the a priori margin for equivalence set at 10%.

Per-protocol analyses included 59 patients in each group (data were incomplete for 1 patient in each group). Reduction in pain score after 90 hours of treatment was 44.7 mm for prednisolone and 46.0 mm for naproxen (difference, 1.3 mm; 95% confidence interval [CI], –9.8 to 7.1), suggesting equivalence. Difference in the size of change in pain was 1.57 mm (95% CI, –8.65 to 11.78).

Both groups had similar adverse effects, which were minor and had resolved by 3-week follow-up.

"Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days," the study authors write. "The present study provides a strong argument to consider prednisolone as a first treatment option in patients with gout."

Limitations of the study include small sample size, assessment of complete relief of symptoms at 90 hours based solely on patients' self-reporting at 3 weeks, disability outcomes assessed with nonvalidated scales, and study population limited to white Dutch people.

"In addition to better safety, the direct drug costs would also be less if systemic corticosteroids (such as prednisolone) were first-line drug choice," the study authors conclude. "In the context of economic benefits, the additional costs of gastroprotective drugs added to NSAID-treatment, should also be taken into account."

The Rheumatology Research Fund Arnhem, the Netherlands, supported this study. The study authors have disclosed no relevant financial relationships.

In an accompanying editorial, Timothy H. Rainer, MD, and Colin A. Graham, MPH, from the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, call the results of this study "useful and important information to front-line staff who manage patients presenting with acute joint pain."

"Clearly this study needs to be repeated in other locales with different incidences of gastrointestinal disease," Dr. Rainer and Mr. Graham write. "Changes in clinical practice often need strong marketing forces, which might not be forthcoming unless drug companies stand to benefit from newer and more expensive drugs. Nevertheless Janssens' 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."

Dr. Rainer and Mr. Graham have disclosed no relevant financial relationships.

Lancet. 2008;371:1816-1818, 1854-1860.

Clinical Context

Currently, the first choice of drug treatment of gout is NSAIDs, despite their gastrointestinal tract and cardiovascular risks. These adverse events are of particular concern in patients with gout, most of whom are middle aged or elderly and many of whom have comorbid renal and cardiovascular conditions.

In this patient population, systemic corticosteroids might be a safer option, as their adverse effects such as osteoporosis, fluid retention, and hyperglycemia typically occur only with chronic use. The only evidence on the effectiveness of systemic corticosteroids for gout is from 3 studies included in a recent systematic Cochrane review. The goal of the present study was to determine whether oral prednisolone is equivalent to naproxen in patients with confirmed gouty arthritis.

Study Highlights

• This double-masked, active-comparator, equivalency trial conducted in the Netherlands used computer-generated randomization.
• Of 381 primary-care patients referred to the trial center with suspected monoarthritis, 120 (32%) entered the trial.
• Inclusion criterion was monoarticular gout confirmed by the presence of monosodium urate crystals.
• A quarter of eligible patients were excluded because of direct safety risks if they would have been treated with naproxen. These risks included serious renal diseases, other serious comorbidity, history of upper gastrointestinal tract ulcer or bleeding, and current anticoagulation.
• Mean age of the participants was 57 years, 53% had hypertension, and 19% had cardiovascular morbidity.
• Participants were randomized to receive either prednisolone (35 mg once a day; n = 60) or naproxen (500 mg twice a day; n = 60) for 5 days.
• The main endpoint was pain intensity measured on a 100-mm visual analog scale. The a priori margin for equivalence was set at 10%.
• Analyses were per protocol and by intent-to-treat.
• Data were incomplete for 1 patient in each group, leaving 59 patients in each group for per-protocol analyses.
• After 90 hours of treatment, reduction in pain score was 44.7 mm for prednisolone and 46.0 mm for naproxen (difference, 1.3 mm; 95% CI, –9.8 to 7.1), suggesting equivalence.
• Difference in the size of change in pain was 1.57 mm (95% CI, –8.65 to 11.78).
• On day 4, 47 (80%) in the prednisolone group and 52 (87%) in the naproxen group had clinically significant improvement, and 13 (22%) and 10 (17%) had complete relief of symptoms.
• Telephone interview revealed that all patients were free of complaints after 3 weeks.
• Adverse effects were similar in both groups, were minor, and resolved by 3-week follow-up.
• No adverse effects were reported in 39 (66%) patients taking prednisolone and 37 (63%) taking naproxen (P = 0.42). The numbers of adverse events were not significantly different between the 2 treatment groups.
• The investigators concluded that oral prednisolone and naproxen are equally effective in the initial treatment of gouty arthritis at 4 days and that this study provides a strong argument to consider prednisolone as a first-line treatment option in patients with gout.
• Limitations of the study include small sample size, reliance on self-report for symptom relief, disability outcomes assessed with nonvalidated scales, and study population limited to white Dutch people.

Pearls for Practice

• Oral prednisolone and naproxen were equally effective in the initial treatment of gouty arthritis at 4 days. The investigators suggest that this study provides a strong argument to consider prednisolone as a first-line treatment option in patients with gout.
• Adverse effects were similar in both oral prednisolone and naproxen groups, were minor, and had resolved by 3-week follow-up.

Legal Disclaimer

• CME Information
• Earn CME Credit »