Treatment for toe bending disease may be ‘mysterious’

Researchers have praised progress in treating a common, incurable disease that causes hand deformities by forcefully bending fingers in the palm of the hand.

A clinical trial at the Universities of Oxford and Edinburgh found that a drug used to treat rheumatoid arthritis appears to push Dupuytren’s disease in the opposite direction when used early, a finding that has been described as a potential ‘mass changer’ for patients.

“We are very keen to follow up on that,” said Professor Jagdeep Nanshahal, the surgeon scientist who led the trial at the Kennedy Institute of Rheumatology in Oxford. “This is a very safe drug and it is important that patients have access to treatment if it is likely to be effective.”

The disease is named after the French surgeon Baron Dupuytren, who obtained the arm of a dead man he had “keeped watching,” as well as claiming the honor of treating Napoleon’s hemorrhoids, not wanting to lose the opportunity to investigate his permanently retracted fingers. Dupuytren’s disease affects around 5 million people in the UK, half of whom have the early stage of progressive disease.

Dupuytren’s disease is largely genetic and is more common in people of Northern European ancestry. Although some call it “Viking disease,” there is no genetic evidence to support its link. It often runs in families, but the exact cause is unclear with factors such as alcohol and tobacco use, diabetes, age and gender appearing to contribute. Men are eight times more likely to have Dupuytren’s disease than women, and in Western countries the prevalence rises from about 12% to 29% between ages 55 and 75.

“The problem for patients with flexed fingers is that they interfere with daily life: putting your hand in your pocket because it’s holding it, wearing gloves, it can be difficult to use the keyboard, even drive,” Nanshall said. Although it was more common in the past, some patients with severe and painful Dupuytren’s condition still required amputation.

The disease is a localized inflammatory disorder that develops when immune cells in the hand prompt the production of fibrous scar tissue. This creates lumps or nodules in the palm of the hand. Sometimes the disease stops there, but it can progress, forming strong cords under the skin that steadily contract and pull one or more fingers into the palm.

The lack of effective treatment for early-stage Dupuytren’s disease means that most patients are asked to wait until their fingers are sufficiently bent to qualify for surgery. While tissue can be cut, there is a risk of nerve and tendon damage, and the disease returns in about a fifth of patients within five years. Another option is to use a needle to puncture the rope and then wrap it, but the ropes usually grow back.

The Oxford group wrote in the Lancet Rheumatology how injecting adalimumab, a drug used for rheumatoid arthritis and Crohn’s disease, into the nodules reduced their size and stiffness compared to an injection of placebo. Volunteers received one injection every three months for a year. Follow-up examinations showed that the lumps continued to shrink for nine months after the final injection. The drug, which costs a £350 injection on the NHS, blocks signals from immune cells that tell myofibroblasts to produce fibrous tissue.

“We know the effect lasts for up to nine months after the last injection, but assuming the nodule begins to grow again at some point, then if approved, the patient will go back for four more injections,” Nanshall said. Similar injections can help reduce recurrence of cord injury after needlestick or surgical treatment.

Nanshahal discusses the data with the Medicines and Healthcare products Regulatory Agency to understand the evidence they need to approve treatment. Ideally, patients would be followed for 10 years to see if adalimumab prevents hand abnormalities, but Nanchahal said this is impractical. “We did our best on patients within a reasonable time frame. We measured everything we could think of,” he said.

Professor Chris Buckley, director of clinical research at the Kennedy Institute, said the drug could be a “game-changer” and prevent the disease from progressing to the point where patients need surgery.

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Professor Neil Millar, an orthopedic surgeon at the University of Glasgow, said the finding “could be very significant” in time. “This is a huge step forward in understanding the disease, but long-term evaluation is required if we are to achieve this as a treatment,” he said.

Professor David Warwick, Dupuytran’s specialist hand surgeon at University Hospital Southampton, said: “Although these are early results, this project is exciting and important as it addresses cell biology.

“The needles are simple and usually effective for a while, but the cord comes back. Usually the surgery is successful but it takes a while to recover and sometimes there are problems. But suppose we can treat Dupuytren before he gets that far by addressing the cell biology? Now that It would truly change Dupuytren’s world.”

2022-05-05 21:22:00

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