Researchers from the University of Oxford have demonstrated that a drug called adalimumab might hold promise as a treatment for early-stage Dupuytrens after a successful phase 2 clinical trial. They found that the patients receiving adalimumab experienced softening as well as a reduction in the size of the treated nodules on their disease-affected hands. The trial's findings are reported in The Lancet Rheumatology.
"This phase 2b trial represents the clinical translation of our laboratory findings, where we identified [tumor necrosis factor] TNF as a potential therapeutic target followed by a phase 2a dose ranging trial which showed that the highly concentrated formulation injected directly into the diseased tissues was effective in downregulating myofibroblasts, the cells responsible for fibrosis," said Oxford Professor, Jagdeep Nanchahal, in a statement.
Dupuytren's disease (also known as Dupuytren's Contracture) affects more than 8 percent of the global population and is thought to be hereditary as it most commonly runs in families. The disease normally affects men more than women and tends to start in midlife with gradual thickening of the skin on the palm of the hand and at the base of the fingers. Contributing factors, such as smoking or drinking excessive amounts of alcohol can further worsen and accelerate the disease.
During the early stages, patients can normally feel hard nodules or thickened cords developing on the palm of their hands, and as time proceeds, these nodules and cords continue to harden and eventually becomes so stiff that the fingers start to curve inwards and eventually become contracted and unable to straighten anymore. The little and ring fingers are most commonly involved in finger contractures.
There’s currently no cure for the disease, only remedial treatment options such as surgery to help straighten the fingers, but that's normally not offered during the early stages of the disease as there is a high likelihood of the disease returning after surgery. Low levels of radiotherapy may also help during the early-stage Dupuytren's, however, it's not widely offered by healthcare systems. Now, researchers are possibly one step closer to an alternative treatment for early-stage Dupuytren's disease that could prevent the disease from advancing.
In the latest trial, researchers recruited 140 participants with early-stage Dupuytren's disease. The participants were randomized into two groups: both received four injections into the nodules and cords of affected hands every three months, but one group received 40 milligrams adalimumab in 0.4 milliliters, while the other received a saline solution. The outcome of the trial was to assess the hardness of the nodules and cords in the hands after 12 months, and the patients were followed up for 18 months to assess their overall outcomes after the injections ceased.
The drug adalimumab works specifically on cells called myofibroblasts, which are the cells involved in causing the hardened tissue in the hands of patients. The researchers found that injecting the drug directly into the hardened tissue downregulates myofibroblasts and reduces the size of and softens the hardened tissue.
The trial was safe and no serious adverse reactions were reported according to the findings. More noticeably, the researchers saw lasting improvements in the softening of the hardened tissue after the 18-month period follow-up, suggesting it could be a sustained treatment option going forward that could prevent patients' fingers to become contracted.
"This could be a game-changer for patients who suffer from this disabling condition," Professor Chris Buckley, Director of Clinical Research at the Kennedy Institute at Oxford stressed. "Dupuytren's disease is easy to spot at an early stage, so by starting a course of anti-TNF injections could bring long lasting respite and prevent the disease advancing to the stage that surgery is needed."