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Abstract
Objectives To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the ‘start-low go-slow’ dose approach.
Methods A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months.
Results Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo.
Conclusions Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the ‘start-low go-slow’ strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period.
Trial registration number ACTRN 12618001179224.
- Gout
- Crystal arthropathies
- Therapeutics
Data availability statement
Data are available on reasonable request. Analysed data may be made available to external collaborators on reasonable request following review by the trial steering committee with appropriate acknowledgements.
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Data availability statement
Data are available on reasonable request. Analysed data may be made available to external collaborators on reasonable request following review by the trial steering committee with appropriate acknowledgements.
Footnotes
Handling editor Josef S Smolen
Contributors LS, CF and ND: Substantial contributions to the conception or design of the work; acquisition, analysis or interpretation of data for the work; Drafting the work or revising it critically for important intellectual content; final approval of the version to be published. AH, BM, JD, JH and PTC: Substantial contributions to the conception or design of the work; acquisition, of data for the work; final approval of the version to be published. LKS and ND are responsible for the overall content as the guarantors.
Funding The study was funded by the Health Research Council of New Zealand (18/151).
Competing interests All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: LS has received consulting fees from Pharmac and royalties from Up-to-Date outside this work. ND has received consulting fees, speaker fees or grants from AstraZeneca, Novartis, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma outside the submitted work.; no other relationships or activities that could appear to have influenced the submitted work. The other authors report no competing interests.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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