Dupuytren’s disease (DD) affects 12% of people over the age of 55 in the Western world,1
and 35-50% of those with early DD nodules progress to developing contractures.2,3
There is currently no approved therapy for treatment for early-stage DD. Studies reporting the efficacy of intranodular injection of steroids or radiotherapy are limited by a lack of quality, with no blinding or randomisation, and the use of subjective outcome measures.4
The cell responsible for deposition of the excessive collagenous matrix and contraction in all fibrotic conditions, including DD, is the myofibroblast, characterised by the expression of α- smooth muscle actin (α-SMA). We found that TNF promoted the development of myofibroblasts. Treatment with anti-TNF resulted in a dose-dependent reduction in contractility, with a concomitant reduction in expression of α-SMA.5
We injected nodules of patients scheduled to undergo surgical excision 2 weeks later with adalimumab or an equal volume of placebo in 3 dose cohorts: 15mg in 0.3ml, 35mg in 0.7ml, 40mg in 0.4ml. The latter resulted in downregulation of myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks.6
These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in 181 patients recruited in 3 centres (Oxford, Edinburgh, Gronigen) with early stage Dupuytren's disease.
References are listed here
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