Colchicine for Knee Osteoarthritis — Biomarkers Improved, Pain Did Not

Colchicine changed several inflammatory biomarkers, but after three months it did not reduce pain, improve function or reduce knee effusion more than placebo. This is an important negative clinical result: a favourable laboratory signal does not necessarily translate into a benefit that patients can feel.

Why is this study interesting?

Synovitis and innate immune activation are involved in the pathophysiology of knee osteoarthritis, making colchicine a plausible drug-repurposing candidate. It affects several inflammatory pathways and is well established in gout and pericarditis, yet previous osteoarthritis studies have been inconsistent.

The CLOAK trial, published online on 23 August 2026 in Seminars in Arthritis and Rheumatism, assessed not only pain and function but also ultrasound-detected effusion and a panel of biological markers. This allowed the investigators to compare clinical outcomes with biochemical effects.

Question and methods

The trial included 120 people with symptomatic Kellgren–Lawrence grade 2 or 3 knee osteoarthritis. Participants were randomly assigned to daily colchicine or placebo for three months. The study used double blinding, and concomitant non-steroidal anti-inflammatory drugs were not permitted.

The primary endpoint was the between-group difference in change in visual analogue scale pain in the index knee. Secondary outcomes included KOOS, ultrasound-measured effusion depth, paracetamol use and changes in markers associated with inflammation and osteoarthritis.

Results

At three months, colchicine was not superior to placebo for pain reduction. There was also no advantage in KOOS or ultrasound-detected effusion. No clinically meaningful difference emerged in subgroup analyses of participants with greater pain, more advanced radiographic disease, higher hsCRP or higher uric acid.

At the same time, the colchicine group showed favourable changes in some biomarkers. Statistically significant between-group differences included hsCRP and beta-NGF. For several additional markers the authors reported only trends; these signals should not be treated as proof of clinical benefit.

Clinical interpretation for an orthopaedic surgeon

The most important finding is the absence of improvement in outcomes that matter directly to patients. A biomarker shift may indicate biological activity, but it is not enough to justify treatment when pain, function and effusion do not improve.

The study does not support starting colchicine solely to treat symptomatic knee osteoarthritis. For a patient taking colchicine for another recognised indication, these results of course do not imply that the drug should be stopped; the trial addresses its effectiveness as a treatment for knee osteoarthritis.

Limitations

• A three-month follow-up cannot assess long-term effects or structural progression.
• A sample of 120 may miss small treatment effects and uncommon adverse events.
• Exclusion of concomitant NSAID use limits direct generalisation to some routine clinical settings.
• Multiple biomarker analyses increase the chance of false-positive findings.
• Biochemical change remains a surrogate outcome, not evidence of patient benefit.

What might this change in practice — and what does it not prove?

The findings strengthen the case against routine colchicine use for symptomatic knee osteoarthritis outside another accepted indication or a clinical trial. They also reinforce an important hierarchy of evidence: pain, function and safety should carry more weight in treatment decisions than improvement in an isolated biomarker.

The trial does not prove that colchicine has no anti-inflammatory biological effect or that longer treatment could never produce benefit. It does show that there is currently no clinical basis for waiting for such an effect at the expense of better-supported care. Appropriate exercise and loading, education, weight management, analgesic strategies that respect contraindications, and surgery for properly selected patients remain central to practice.

Source

Samuels J, Tse K, Wei D, et al. CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study. Semin Arthritis Rheum. 2026;153066. DOI: 10.1016/j.semarthrit.2026.153066. PubMed.

Polish version · Research Updates, Literature and Evidence-Based Medicine

Content prepared by: Tomasz Poboży - orthopaedic surgeon.