Oral Steroids, NSAIDs Equally Safe, Effective for Acute Gout

Janis C. Kelly

February 23, 2016

Acute gout pain was controlled equally well by oral steroids or by nonsteroidal anti-inflammatory drugs (NSAIDs), so treatment choice should be guided mainly by the characteristics and comorbidities of the individual patient, researchers report in an article published online February 23 in the Annals of Internal Medicine. The double-blind, randomized trial assessed pain outcomes for 376 patients who presented to emergency departments (EDs) within 3 days of symptom onset.

The finding that oral prednisolone and oral indomethacin were equally effective and safe at reducing pain indicates that a rethinking of assumptions about oral steroids and gout is in order, lead author Timothy Hudson Rainer, MD, professor of emergency medicine, Cardiff University, United Kingdom, told Medscape Medical News.

"The main concerns with steroids relate to adverse effects associated with long-term use," Dr Rainer said. "Once these concerns are embedded in a physician's psyche, they are hard to dislodge. However, the greater the evidence base, the greater the chance that there will be a change in view and in guidelines. The other concern is that steroids may hinder the body's immune response to infection. Therefore, if infection is associated with the patient's illness, steroids may hinder the recovery. This concern seems more theoretical than practical."

Dr Rainer and colleagues randomly assigned patients who presented to an ED with acute arthritis suggestive of gout to 5 days of active treatment with indomethacin (50 mg three times a day) or with oral prednisolone (30 mg/day), along with placebo tablets in each case.

Eligibility included rapid onset of severe pain, swelling, tenderness, and erythema of the affected joint, peaking at 6 to 12 hours after onset, plus at least one of the following: metatarsophalangeal joint involvement; knee, ankle, wrist, or elbow involvement with gouty tophi; previous joint aspiration that had confirmed gout; hyperuricemia; or a clinical history of one or more gouty arthritis attacks. Patients who did not have at least one of these symptoms were assessed by microscopic examination of joint fluid for presence of monosodium urate crystals. Most patients were men, mean age was 65 years, 50% had hypertension, 35% had a history of hyperuricemia, 13% had a history of renal insufficiency, 74% had a history of recurrent gout, 83% presented with monoarthritis, and 9% used allopurinol.

The study included patients from four of the 17 acute hospitals in Hong Kong, and the authors note that a high proportion of patients with gout in Hong Kong visit EDs for care because of a lack of availability of outpatient care by primary care physicians. The four hospitals in the study treat about one third of the 2 million patients who visit Hong Kong EDs each year.

Pain in the worst affected joint was measured at rest and during movement on a 0- to 100-mm visual analogue scale. Clinically significant change in pain level was defined as ±13 mm on a 100-mm visual analogue scale. The researchers analyzed pain changes during the 2 hours in the ED and pain change per day during days 1 to 14 of the post-ED phase.

The researchers found similar pain reductions with indomethacin and prednisolone during the 2 hours of ED treatment. At rest, the mean decrease in pain score was 6.54 mm/hour (95% confidence interval [CI], 5.02 - 8.06 mm/hour) for indomethacin and 5.05 mm/hour (95% CI, 3.56 - 6.55 mm/hour) for prednisolone (mean difference, −1.49 mm/hour; 95% CI, −3.61 to 0.64 mm/hour; P = .69). With movement, the mean decrease in pain score was 11.69 mm/hour (95% CI, 10.10 - 13.28 mm/hour) for indomethacin and 11.38 mm/hour (95% CI, 9.98 - 12.79 mm/hour) for prednisolone (mean difference, −0.31 mm/hour; 95% CI, −2.42 to 1.80 mm/hour; P = .56).

For days 1 to 14 after ED treatment, the mean decrease in pain score at rest was 1.80 mm/day (CI, 1.46 - 2.13 mm/day) for indomethacin and 1.68 mm/day (CI, 1.39 - 1.97 mm/day) for prednisolone (mean difference, −0.12 mm/day; P = .80). Mean decrease in pain score with activity was 2.96 mm/day (CI, 2.62 - 3.30 mm/day) for indomethacin and 3.19 mm/day (CI, 2.85 - 3.52 mm/day) for prednisolone (mean difference, 0.22 mm/day; CI, −0.25 to 0.70 mm/day; P = .20).

The authors write, "Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED."

There were no major adverse events in either treatment group. During the ED phase, indomethacin was associated with more minor adverse events than prednisolone (19% vs 6%; P < .001), but during days 1 to 14 after ED treatment, both groups had minor adverse events rates of 37%.

Dr Rainer said, "We were surprised that there were no serious adverse events associated with either of the medications. Previous studies suggested that a small proportion of patients might develop gastrointestinal hemorrhage with NSAIDs. However, none were observed in our study."

The authors acknowledge that one study limitation is that gout diagnosis was usually based on clinical criteria, rather than joint fluid analysis. Dr Rainer said, "An accurate, noninvasive, clinical method for discriminating gout from other causes of arthritis would improve diagnosis in a real-world setting. At the moment, such diagnoses are guesstimates, rather than proven."

Dr Rainer also noted that lack of an all-placebo group (which would be difficult to include because of ethical concerns) left some unanswered questions. He said, "The remarkable synchrony of reduction in pain in both groups over 5 days did make us wonder whether this was a process of natural recovery, rather than anything to do with the medication. In order to confirm this, there would probably need to be a placebo arm in any future study."

Gout expert Jasvinder Singh, MD, MPH, who was not involved in the study, told Medscape Medical News that the trial was well-designed and adds evidence that steroids are not inferior to NSAIDs for relieving the pain of acute gout.

"The clinical implication is that the choice of steroids or NSAIDs should be individualized for each acute gout patient," Dr Singh said. "Some patients will express a preference for one approach or the other, based on their past experience, but the major consideration should be the patient's comorbidities. Severe diabetes, serious infection, or open wounds would be indications for choosing NSAIDs. A history of gastrointestinal bleeding, NSAID-associated renal failure, bad kidneys, or advanced age would point toward steroids as the better option." Dr Singh is professor of medicine, University of Alabama at Birmingham School of Medicine.

Dr Singh also said the study included only patients in Hong Kong, which presents a "slight caveat" to generalizing the findings to other populations, but that there are no published data suggesting that the efficacy of either prednisolone or indomethacin is affected by country of residence or ethnicity.

The study was supported by the Health and Health Services Research Grant Committee of the Hong Kong Government. The authors and Dr Singh have disclosed no relevant financial relationships.

Ann Intern Med. Published online February 23, 2016. Abstract


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