Two randomized trials presented at the American College of Rheumatology (ACR) annual meeting have cast doubt on the efficacy of colchicine and a combination of herbal supplements for treating osteoarthritis (OA). The studies found neither treatment to be superior to placebo in relieving pain or improving function in patients with knee and hand OA, respectively.
Colchicine for Knee Osteoarthritis
Jonathan Samuels, MD, of NYU Langone Health, presented findings from the CLOAK trial, which investigated colchicine's potential to alleviate knee OA symptoms. The rationale behind the trial was based on the evolving understanding of OA as a disease involving low-grade chronic inflammation. Colchicine, known for its immunomodulatory effects, including inhibition of macrophages and neutrophils, was hypothesized to target these inflammatory processes.
The CLOAK trial enrolled 120 patients with knee OA, randomizing them to either daily colchicine or placebo for 12 weeks. Patients were required to abstain from NSAIDs, intra-articular injections, supplements, acupuncture, or any other new pain medications during the study. The primary outcome was the change from baseline in the Knee Injury and OA Outcome Score (KOOS).
The results indicated that both groups improved nearly equally, with the placebo group showing a slightly greater numerical advantage. Specifically, the placebo group showed a decrease of about 1.4 points compared with 1.0 in the colchicine group. Subgroup analyses did not identify any group benefitting more from colchicine than placebo. Samuels noted that a limitation was that the drug supplier lost access to the original 0.8-mg dose and had to substitute a dose of 0.6 mg partway through.
Herbal Supplements for Hand Osteoarthritis
Xiaoqian Liu, MD, of the University of Sydney, reported on a trial evaluating a combination of herbal supplements for hand OA. The supplements included curcumin, pine bark extract, methylsulfonylmethane (MSM), and Boswellia serrata extract. Previous low-quality studies had suggested these components might be effective in hand OA.
The study enrolled 106 patients in Australia with hand OA, who were randomized to receive either the supplement cocktail or placebo for 12 weeks. The primary outcome was the change from baseline in a 100-point, patient-reported hand pain scale.
Similar to the colchicine trial, both the active-treatment and placebo groups showed similar degrees of improvement in pain after 12 weeks, with a numerical advantage for placebo (-8.6 points for the supplement cocktail and -14.6 points with placebo) that fell short of statistical significance. Scores on other measures, including the Functional Index of Hand OA, the Patient's Global Assessment, and a quality-of-life scale, all improved to similar degrees in the two study arms.
Liu mentioned that the study, which was largely conducted online, required a good level of technology literacy and skill. The COVID-19 pandemic and a major wildfire affecting many participants might have had both mental and physical consequences for patients.
Implications and Limitations
Both studies faced limitations, including the relatively short 12-week duration, which may not have been sufficient to observe potential benefits, particularly for colchicine's hypothesized effects on disease progression. The COVID-19 pandemic also presented challenges for both trials.
These negative results underscore the ongoing need for effective treatments for osteoarthritis that go beyond simple pain relief and address the underlying disease process. Current medications like NSAIDs and opioids have significant side effects with chronic use, and injectables offer only temporary relief without halting disease progression.
