Colchicine eases inflammation, high bone turnover makers in osteoarthritis
Low-dose oral colchicine appears to be effective at controlling knee osteoarthritis (KOA) progression and severity by reducing inflammation and high bone turnover markers, according to a recent Singapore study. On the other hand, it does not improve KOA symptoms in the short term.
“The present study indicates that colchicine is not effective in reducing symptoms of KOA over a 16-week period compared with placebo. Colchicine was associated with significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) and synovial fluid (SF) C-terminal crosslinked telopeptide of type I collagen (CTXI), and nonsignificant reductions in SF proinflammatory biomarkers,” researchers said.
“These results raise the intriguing possibility that colchicine may have slow-acting disease modification potential in OA,” they added.
For the double-blind, placebo-controlled, randomized trial, 109 symptomatic KOA patients were randomized to receive 0.5 mg of oral colchicine twice daily (n=54) or placebo (n=55). A statistically comparable number of participants achieved the primary outcome of ≥30-percent improvement in total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index; 38.9 vs 49.1 percent; p=0.284). [Osteoarthritis Cartilage 2018;doi:10.1016/j.joca.2018.01.026]
Moreover, the odds of achieving the primary outcome by study end was 0.58 (95 percent CI, 0.27–1.29; p=0.184). None of the posthoc subgroup analyses yielded a significant change in the results.
The current findings are in contrast with previous, smaller randomized controlled trials, which report significant symptom alleviation in response to colchicine. The reason for this discrepancy, researchers said, may be the high placebo response relative to treatment.
“The limitations of this study included small sample size and a lower than expected effect size in the treatment arm compared to the placebo arm, and therefore rendering it underpowered to detect differences based on the observed high placebo response,” said researchers.
“Future studies should incorporate measures to minimize the placebo effect in attempts to better assess drug-placebo differences,” they added.
Researchers also collected blood, urine and SF samples to assess the effect of colchicine on biomarker levels. Changes in WOMAC score was also evaluated. The trial was performed at a single tertiary rheumatology centre in Singapore.
The findings for the secondary outcomes show that while colchicine was no better than placebo, WOMAC scores for pain and function showed significant improvements from baseline at 16 weeks (p<0.001).
Notably, colchicine treatment resulted in a significant decrease in mean levels of serum hs-CRP (3.88±5.45 vs 2.92±4.97 mg/L; mean difference in change scores, –3.16; –5.56 to –0.75; p=0.011) and SF CTXI (0.36±0.60 vs 0.27±0.15; mean difference in change scores, 0.13; 0.04–0.22; p=0.004) by week 16 relative to the placebo group.
On the other hand, mean levels of SF interleukin-6, -8 and -18, tumour necrosis factor α, and CD14 were reduced in the colchicine group, but the difference did not reach statistical significance.
“Given the safety of standard clinical doses of colchicine in this and other studies, and the relative contraindication of standard NSAIDs for some patients, long-term colchicine could warrant further consideration for evaluation of disease modifying effects in KOA,” said researchers.