Compared with low-dose colchicine, naproxen therapy for gout flares was associated with fewer side effects, less analgesic use, and slightly lower costs, according to research results published in the Annals of the Rheumatic Diseases.
Researchers conducted the randomized, multicenter, open-label, pragmatic CONTACT trial (Colchicine or Naproxen Treatment for ACute Gout; ClinicalTrials.gov Identifier: NCT01994226) to compare the clinical effectiveness of naproxen with low-dose colchicine for pain reduction in primary care. Investigators also evaluated the side-effect profiles and cost effectiveness associated with each treatment.
Patient data from 100 general practices across England were collected. All patients were randomly assigned 1:1 to receive either a single initial dose of oral naproxen 750 mg followed by 250 mg every 8 hours for 7 days or oral colchicine 500 mcg 3 times/d for 4 days. Primary outcome included change in worst change intensity (0-10 scale) in 24 hours from baseline measured daily over the first 7 days; mean change from baseline was evaluated in both groups from day 1 to 7 by intention-to-treat.
In total, 399 patients were included in the study (200 received naproxen and 199 received colchicine). Both groups were similar at baseline, although investigators noted that more patients reported experiencing their first-ever gout flare within the colchicine group. Outcome data were collected for 86.0% and 86.5% of patients in the naproxen group at 7 days and 4 weeks, respectively, and 88.9% in the colchicine group at both 7 days and 4 weeks.
Within-group improvements in the primary outcome were seen in both groups during the first 7 days (adjusted mean difference, -0.18; 95% CI, -0.53 to 0.17; P =.32). Results of both unadjusted estimates and multiple imputation evaluation with extended covariate adjustment were similar, with only a small between-group difference in favor of naproxen on day 2.
According to per-protocol analyses, researchers found comparable between-group mean differences in the intention-to-treat evaluation both overall and on days 1 to 6, but found “small significant differences” in favor of naproxen at week 4.
There were no between-group differences in complete pain resolution or patient global assessment of treatment response at any time point. In addition, at week 4, there were no between-group differences in the percentage of patients reporting a relapse or recurrent gout flare, consulting a general practitioner, practice nurse, or emergency department, or taking time off work.
Compared with patients in the naproxen group, more patients in the colchicine group used paracetamol or codeine during days 1 to 7. At week 4, ibuprofen use was more common in the colchicine group.
During the study period, 3 serious adverse events were noted, although none were related to trial interventions; there were no deaths reported.
Researchers also noted that naproxen was slightly less costly (80% chance) and more effective than colchicine.
Study limitations included the potential misclassification of gout diagnosis, the open-label study design, and the collection of self-reported outcomes.
“While randomized trials have compared [nonsteroidal anti-inflammatory drugs] (NSAIDs) and prednisolone, future research should compare the effectiveness and safety of colchicine and corticosteroids, particularly in patients with contraindications to NSAIDS,” the researchers concluded. “In the absence of contraindications, naproxen should be used ahead of low-dose colchicine 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 [published online October 30, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216154