BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.

“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.

The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.

Current guidelines in the United Kingdom suggest that an NSAID or low-dose colchicine can be considered equally for the first-line treatment of acute gout, Dr. Roddy said, yet their “effectiveness and safety have never been directly compared in a randomized controlled trial.” (The 2012 American College of Rheumatology recommendations for initial pharmacologic treatment of an acute attack of gout also advise equally considering an NSAID or oral colchicine or systemic corticosteroids.)

CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.

“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.

Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.

After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.

The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).

The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.

Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.

During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).

Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).

There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.

Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).

Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).

Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.

The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.

rhnews@frontlinemedcom.com

Trial supports naproxen over low-dose colchicine for acute gout