About This Webinar
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.

The handout for this session is available by clicking the handout icon on the bottom right-hand corner of the video player
Presenter
  • 1609259086-ce1fd4f14551a949
    Professor Jagdeep Nanchahal
    Professor of Hand, Plastic and Reconstructive Surgery, The Kennedy Institute of Rheumatology, University of Oxford

    Jagdeep Nanchahal is a surgeon scientist focussing on defining the molecular mechanisms of common diseases and translating his findings through to early phase clinical trials.

    His research is focussed on promoting tissue regeneration by targeting endogenous stem cells and reducing fibrosis. In 2013 his group identified TNF as a therapeutic target for Dupuytren’s disease. He is currently leading a phase 2b clinical trial funded by the Wellcome Trust and Department of Health to assess the efficacy of local administration of anti-TNF in patients with early stage Dupuytren’s disease. He has also obtained funding from the NIHR to investigate the efficacy of anti-TNF for early-stage frozen shoulder. His group has also identified a novel mechanism for promoting repair and regeneration of multiple tissues by targeting endogenous stem cells.

    He is a proponent of evidence-based medicine and was the only plastic surgery member of the NICE Guidance Development Groups on complex and non-complex fractures (2013-2016).