In patients with knee osteoarthritis (OA), treatment with colchicine reduced inflammation and high bone turnover, both of which are associated with disease progression. However, colchicine did not relieve short-term symptoms of knee OA, according to the results of the COLKOA trial (ClinicalTrials.gov identifier: NCT02176460) published in Osteoarthritis Cartilage.

The investigators conducted the double-blind, placebo-controlled, randomized COLKOA trial to evaluate the effectiveness of colchicine on pain and function in knee OA. They compared 16 weeks of treatment with twice-daily orally administered colchicine 0.5 mg vs placebo in patients with knee OA. The primary outcome was ≥30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 16 weeks in the signal knee. Researchers also assessed a number of secondary end points, including change in WOMAC pain score and physical function, and results of the Health Assessment Questionnaire and the Outcome survey short-form 36 version 2. Additional secondary end points included quantity of rescue paracetamol used, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responder criteria, and treatment-related changes in all biomarkers.

A total of 109 randomly assigned participants were enrolled in the trial, with 54 receiving colchicine and 55 receiving placebo. The mean age of the participants was 58.5±8.7 years and 70.6% were women. Participants had moderate-severity knee OA, and approximately one-quarter were taking regular doses of paracetamol and nonsteroidal anti-inflammatory drugs.


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Overall, 44.0% of the patients met the primary outcome. In the intention-to-treat model, 38.9% of participants in the colchicine arm and 49.1% of participants in the placebo arm met the primary end point at the end of the study (P =.284). When colchicine was compared with placebo, the odds of achieving the primary response were 0.58 (95% CI, 0.27-1.29; P =.184).

In the as-per-protocol analysis (n=97), 41.2% and 56.5% of participants in the colchicine and placebo groups, respectively, met the primary outcome at the end of the study. The odds of achieving the primary response were 0.54 (95% CI, 0.22-1.30; P= .131).

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The investigators did not identify strong treatment differences for the clinical secondary outcomes. Treatment with colchicine was associated with significantly reduced mean levels of serum high-sensitivity C-reactive protein (P =.008) and synovial fluid (SF) C-terminal cross-linked telopeptide of type I collagen (P =.002). Moreover, colchicine therapy reduced the level of certain inflammatory markers (SF interleukin [IL]-6, IL-8, IL-18, tumor necrosis factor alpha, and CD14), but the differences between the 2 groups were not significant.

The investigators concluded that the use of low-dose colchicine was not effective in reducing short-term symptoms of knee OA, suggesting that use of the agent may have slow-acting disease modification potential in OA. Long-term use of colchicine might warrant further consideration regarding its disease-modifying effects in knee OA.

Reference

Leung Y-Y, Haaland B, Huebner JL, et al. Colchicine lack of effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): a randomized controlled trial [published online February 7, 2018]. Osteoarthritis Cartilage. doi: 10.1016/j.joca.2018.01.026