Efficacy of Colchicine for the Reduction of Symptoms in Knee Osteoarthritis

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.

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).

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