A phase-2b trial has shown the effectiveness of an anti-tumour necrosis factor drug for treating the disease at an early stage
Results of a phase-2b trial led by researchers at Oxford University’s Kennedy Institute have shown that the anti-tumour necrosis factor (TNF) drug adalimumab is effective for treating early stage Dupuytren’s disease.
Dupuytren’s disease is a progressive condition of the palmar fascia, the layer of fibrous tissue underneath the skin on the palm of the hand. It affects around 5% of the UK population. The disease usually presents with small lumps or nodules on the palm. As the fascia thickens over time, it shortens, causing fingers to contract inwards, interfering with hand function.
There is currently no approved treatment for early stage disease, and patients typically have to wait until the condition has progressed to contractures before surgery can be performed.
The latest trial results showed that patients with early stage disease who received intranodular injections of adalimumab experienced softening and reduction in the size of their nodules. Beneficial effects continued to be seen 9 months after the last injection, indicating a sustained treatment effect.
‘This could be a game changer for patients who suffer from this disabling condition,’ said Professor Chris Buckley, Director of Clinical Research at the Kennedy Institute.
‘Dupuytren’s disease is easy to spot at an early stage, so starting a course of anti-TNF injections could bring long-lasting respite and prevent the disease advancing to the stage that surgery is needed.’
RIDD trial results
Earlier research by the Oxford team leading the study found that myofibroblasts, the cells that produce the excess fibrous tissue responsible for the nodules and contractures in Dupuytren’s disease, are dependent on TNF.
In 2018, a phase-2a trial in patients scheduled to undergo surgery for Dupuytren’s disease indicated that concentrated formulations of adalimumab injected directly into nodules could downregulate the myofibroblast phenotype (as shown by reduced concentrations of alpha smooth muscle actin and procollagen type I proteins).
In this latest phase-2b trial (RIDD; Repurposing Anti-TNF for Treating Dupuytren’s Disease), 140 participants with early stage disease were randomised to receive four intranodular injections at 3-monthly intervals with either adalimumab (40 mg in 0.4 ml) or saline.
The primary outcome was nodule hardness (measured using an instrument called a durometer) at 12 months. A secondary measure of success was a decrease in nodule size on ultrasound. Patients were followed up for a total of 18 months.
The study observed statistically significant decreases in both the hardness and size of nodules in patients receiving adalimumab compared with those receiving a placebo. There were no related serious adverse events; the most common adverse events were minor injection site reactions.
And most significantly, although adalimumab has a mean half-life of only 2 weeks, the researchers saw continued effects for 9 months after the last injections.
‘This suggests a biological effect,’ explained Professor Jagdeep Nanchahal, the study’s lead author. ‘It is quite profound.’
The study authors suggested that, even if nodules were to reactivate, intermittent local injections may be sufficient to control ongoing progression: ‘We would envisage that, following completion of a course of four injections, nodule development could be followed expectantly, and the treatment repeated in the event of reactivation of the disease.’
This article was originally published on Medscape, part of the Medscape Professional Network.
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