In the absence of contraindications, naproxen should be used ahead of low-dose colchicine in the treatment of gout flares in primary care, according to research results published in the Annals of the Rheumatic Diseases. Although there were no significant differences in terms of pain intensity between the 2 treatments, naproxen caused fewer side effects supporting its use as a first-line treatment for gout flares.
Researchers conducted a randomized, multicenter, open-label, pragmatic clinical trial (CONTACT; ClinicalTrials.gov Identifier: NCT01994226) to compare the clinical effectiveness of naproxen with low-dose colchicine in reducing pain from gout flares in primary care. Investigators also assessed the side effect profiles and cost-effectiveness of each treatment.
Participants aged ≥18 years were enrolled in the study from 100 general practices across England, and they had received a clinical diagnosis of gout from their primary care physicians, made without joint aspiration, blood tests, imaging, or diagnostic criteria. Participants were then randomly assigned 1:1 to receive either a single initial oral dose of naproxen 750 mg followed by 250 mg every 8 hours for up to 7 days or oral colchicine 500 mcg every 8 hours for 4 days. On days 0 through 7 and at week 4, participants completed a validated Numeric Rating Scale to rate the intensity of the worst pain experienced in the last 24-hour period, with a primary outcome of change in pain intensity from baseline measured over the first 7 days.
Primary outcome data were available in 86.0% and 86.5% of patients in the naproxen group at day 7 and week 4, respectively, and 88.9% of patients in the colchicine group at the same time points. Investigators noted 30 protocol violations relating to either treatment or eligibility.
Within-group improvements in the primary outcome were seen in both groups over the first week. There were no significant between-group differences in mean change in the worst pain intensity during the first 7 days (colchicine vs naproxen; adjusted mean difference, -0.18; 95% CI, -0.53 to 0.17; P =.32), with similar unadjusted estimates.
Per-protocol analysis demonstrated a comparable between-group mean difference in the intent-to-treat evaluation, and days 1 through 6 showed similar between group differences and small but significant differences in favor of naproxen at week 4. There were no between-group differences in either complete pain resolution or patient global assessment of treatment response at any time point.
Overall, compared with the naproxen group, more participants in the colchicine group received either paracetamol or codeine for gout during the first 7 days. At week 4, ibuprofen use was also more common in the colchicine group in the complete case analysis.
In terms of safety, 3 serious adverse events were reported, but none related to trial interventions. Two patients in the naproxen group and 1 patient in the colchicine group were hospitalized. Over the course of the first week, self-reported diarrhea and headache were more common with treatment with colchicine than naproxen. No deaths were reported.
In addition, compared with colchicine, naproxen was slightly less costly and more effective; naproxen had an 80% chance of being more cost-effective.
Study limitations included the use of clinical gout diagnosis, the open-label study design, and the collection of solely self-reported outcomes.
“We found little difference in pain reduction between naproxen and low-dose colchicine, but naproxen was associated with fewer side effects, lass analgesic use and slightly lower costs,” the researchers concluded,” suggesting that, in the absence of contraindications, naproxen should be used…to treat gout flares in primary care.”
Roddy E, Clarkson K, Blagojevic-Bucknall M, et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Ann Rheum Dis. 2020;79(2):276-284.