Colchicine: It’s an old drug with a new trick

Colchicines, a venerable drug Hippocrates proposed as gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.

“I’m going out on a limb here: Could colchicines improve osteoarthritis pain and function? I won’t tell you to do it, but there is a couple of studies that say it may be of some value – and they intriguing,” said at the symposium, sponsored by the American College of Rheumatology.

Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added by a rheumatologist at New York University.

Research at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchinine or placebo in a double-blind clinical trial. After three months of prospective follow-up, the colchicinie- treated group showed a mean 11.1 point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1 points improvement in controls.

The colchicines group had 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and 1,621 mg in controls.

The Iranian study recapitulates an earlier double – blind randomized trial by the researchers at King George’s Medical College in Lucknow, India.

They randomized 36 patients on background NSAID therapy for OA of the knee to colchicines at 0.5 mg twice daily or placebo.

The co-primary outcomes were the proportions of patients showing at least a 30-percent improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and Mcmaster Universities) osteoarthritis index and visual analog scale for knee pain.

That threshold was achieved in the WOMAC osteoarthritis index by 58 percent of the colchicine group, compared with 24 percent of control, and on the knee pain score by 53 percent of colchicines – treated patients and 18 percent of controls.

The colchicines has well-established anti-inflammatory effects on neutrophills. It curbs tumor necrosis factor – alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing are common in patients with primary OA, and it has been suggested that they activate the inflammasome, which drives production of interleukin -1(1), a key mediator of cartilage breakdown in OA.

Colchicine inhibits this calcium crystal-induced inflammation.

Researchers at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 level and OA severity, they noted.

They proposed that uric acid is released into diseased joints damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic sub acute IL-1-mediated inflammatory.

Gout and OA are fellow travelers, said Dr. Pillinge, who cited a study by his colleague at NYU, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 controls. All were men over age 65.

Those with gout were twice as likely as were controls to meet American College of Rheumatology criteria for OA, and they were more likely to have bilateral knee OA by x-ray.