Drugs target cell pathways altered in scleroderma
Evidence suggests drugs in scleroderma trials have beneficial effects on skin, lung function and the heart.
Changes in cellular pathways in scleroderma are targeted by drugs currently in clinical trials, a joint UCL and Oxford University Hospital study has found, supporting initial evidence that these drugs will have beneficial effects in people with scleroderma. The three drugs Emma Derrett-Smith and colleagues at UCL and Rachel Hoyles from Oxford University Hospitals looked at in a mouse model of scleroderma were nintedanib, tocilizumab and riociguat.
Nintedanib targets growth factor receptors that are involved in the mechanisms by which scarring in the lungs occurs. The use of nintedanib will be compared with placebo in a trial that is currently recruiting patients with scleroderma-related lung disease.2
Tocilizumab targets a protein called IL-6 and reduces inflammation. A trial of subcutaneous tocilizumab in systemic sclerosis found clinically significant improvement in skin sclerosis and lung function.1
Riociguat is used to treat pulmonary arterial hypertension, as it stimulates soluble guanylate cyclase activity, improves smooth muscle growth, reduces platelet clotting in the blood vessels and leads to relaxation of the blood vessels (vasodilation). Pulmonary arterial hypertension affects up to 12% of people with systemic sclerosis. A study on the use of riociguat in people with diffuse cutaneous systemic sclerosis has finished recruiting and is expected to finish in June 2022.3,4
The study by Dr Derrett-Smith and colleagues found between 50 and 400 genes were altered in scleroderma cells and that there were multiple changes in pathways targeted by riociguat, tocilizumab and nintedanib. The results presented in a poster at the British Society of Rheumatology Conference in Birmingham.
Opportunity to take part
The following UK hospitals are or will be recruiting participants for the nintedanib study: Glasgow Royal Infirmary (Glasgow), Glenfield Hospital (Leicester), Royal Free Hospital (London) and Guy's Hospital (London). If you are interested in taking part, contact Boehringer Ingelheim Call Centre (in the USA) on 1-800-243-0127 or email email@example.com
- Khanna D, Denton SP, Jahreis A et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (fascinate): a phase 2, randomised controlled trial. Lancet 2016;387:2630-40
- Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis, NCT02597933
- Efficacy and Safety of Riociguat in Patients with Systemic Sclerosis, NCT02283762
- Distler O, Pope J, Denton C et al. RISE-SSc: Riociguat in diffuse cutaneous systemic sclerosis. Respir Med 2017;122(Suppl 1):S14-S17