Clinical trials: Changing the future of scleroderma

FESCA•Clinical trials and scleroderma•Clinical trials: Changing the future of scleroderma

Clinical trials are essential to help turn new ideas into real treatments and tests for people living with scleroderma.

Without people like you taking part in research we wouldn’t have:

  • Updated clinical guidelines to help doctors give the best possible treatment plans - based on evidence from trials
  • Improved ways to manage tiredness, pain, stiffness and breathlessness
  • Treatments that help protect organs, such as the lungs
  • Better approaches to managing complications with blood vessels, digestion, kidneys, skin, muscles and bones

Why more research is needed

  • We still need to understand what causes the different types of scleroderma – from localised to systemic.
  • We still want more treatments for symptoms – that can be more personalised
  • We still need treatments to slow down disease progression

Clinical trials are increasingly focusing on:

  • Matching treatments to specific disease patterns
  • Using biomarkers - such as antibodies in the blood - to guide therapy
  • Understanding what affects long-term outcomes

Why research projects need you

  1. Scleroderma is rare and complex. Scleroderma is uncommon, affecting between 7 and 44 people in 100,000. This means it can be challenging to find enough people to take part in a trial..
  2. Different types of scleroderma need to be better understood. Researchers are studying the different types of scleroderma (including limited, diffuse, localised and overlap syndromes) because they can affect people in very different ways.
  3. Your unique experience of scleroderma is valuable. Studies may involve people who are newly diagnosed, who are at higher risk, whose disease is stable or in remission, caregivers or family members - every perspective helps to grow understanding.

Why more women are needed in clinical trials for scleroderma

Scleroderma is around four times more common in women than men, especially for diffuse forms of the disease, where the body produces too much collagen that causes thickening, tightening and scarring of the skin and internal organs.

40%

Women have been under-represented in clinical trials for many years. Currently, around 40% of people in randomised controlled trials are female.

So we need more women in scleroderma trials to represent the reality of how many women experience the condition. This supports the development of safer, more reliable and fairer treatment options.

Why more people from diverse ethnic backgrounds are needed in clinical trials for scleroderma

Research shows that scleroderma symptoms and the way the condition progresses can be different in people from diverse ethnic backgrounds.

Large international studies have found differences in:

  • Organ involvement
  • Lung disease risk
  • Blood vessel complications
  • Survival outcomes

Including people from diverse ethnic backgrounds in scleroderma research helps to make sure:

  • that treatment guidelines are fair and accurate
  • health inequalities aren’t widened by evidence gaps.
Sources (25)
  1. Clinical trials: Scleroderma & Raynaud’s UK (SRUK) https://www.sruk.co.uk/research/taking-part-in-research/clinical-trials/“By taking part in or supporting clinical trials, you’ll be helping researchers find the most effective ways to manage the symptoms and impact of scleroderma and Raynaud’s – not just for today, but for the future too.”
  2. 2024 British Society for Rheumatology guideline for management of systemic sclerosis: Rheumatology (Oxford) https://academic.oup.com/rheumatology/article/63/11/2956/7750184“This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives.”
  3. Managing symptoms such as fatigue, pain, stiffness, or breathlessness in systemic sclerosis: RMD Open https://rmdopen.bmj.com/content/11/3/e005776“This review provides an up-to-date synthesis of both current organ-based treatment strategies in major organ domains—skin, ILD, PAH, scleroderma renal crisis, raynaud’s phenomenon and digital ulcers, gastrointestinal and musculoskeletal involvement—and emerging therapies in SSc, with an emphasis on disease-modifying approaches and future directions in personalised care.”
  4. Treatment of systemic sclerosis–associated interstitial lung disease: evidence‑based recommendations: Annals of the American Thoracic Society https://academic.oup.com/annalsats/article/21/1/12/8382072“Summary of: Raghu G, Montesi SB, Silver RM, Hossain T, Macrea M, Herman D, et al. Treatment of systemic sclerosis–associated interstitial lung disease: evidence-based recommendations.”
  5. State‑of‑the‑art evidence in the treatment of systemic sclerosis: Nature Reviews Rheumatology https://www.nature.com/articles/s41584-023-00909-5“Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials.”
  6. Precision medicine and disease subtypes in systemic sclerosis: Nature Reviews Rheumatology https://www.nature.com/articles/s41584-022-00803-6“Increased variability in the natural history of SSc skin disease impedes the identification of treatment-related effects, and strategies for shorter duration trials might improve the separation of treatment effect from variation in disease natural history.”
  7. Biomarkers in systemic sclerosis: Current Opinion in Rheumatology (PMC) https://pmc.ncbi.nlm.nih.gov/articles/PMC7185900/“Several novel biomarkers show promise in improving the assessment of systemic sclerosis (SSc) disease severity, prognosis, and treatment response.”
  8. Predicting the risk of subsequent progression in patients with systemic sclerosis‑associated interstitial lung disease with progression: a multicentre observational cohort study: Lancet Rheumatology https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(25)00026-8/abstract“Systemic sclerosis-associated ILD progression does not predict further ILD progression at the next annual follow-up visit, even in an enriched population, but progression was associated with mortality. These results have implications for clinical practice because they support a paradigm shift in treatment strategy, advocating for initiating therapy in patients at risk of progression.”
  9. Systemic Sclerosis (SSc): European Reference Networks https://reconnet.ern-net.eu/disease-ssc/“The reported prevalence of SSc is 7.2–33.9 and 13.5–44.3 per 100,000 individuals in Europe and North America, respectively. Annual incidence estimates are 0.6–2.3 and 1.4–5.6 per 100,000 individuals in Europe and North America, respectively.”
  10. Clinical trials: Scleroderma & Raynaud’s UK (SRUK) https://www.sruk.co.uk/research/taking-part-in-research/clinical-trials/“By taking part in or supporting clinical trials, you’ll be helping researchers find the most effective ways to manage the symptoms and impact of scleroderma and Raynaud’s – not just for today, but for the future too.”
  11. Systemic Sclerosis: MSD Manual Professional Edition https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/systemic-rheumatic-diseases/systemic-sclerosis“Systemic sclerosis is classified as: Limited cutaneous systemic sclerosis (CREST syndrome); Diffuse cutaneous systemic sclerosis; Systemic sclerosis sine scleroderma.”
  12. Clinical trials: Scleroderma & Raynaud’s UK (SRUK) https://www.sruk.co.uk/research/taking-part-in-research/clinical-trials/“By taking part in or supporting clinical trials, you’ll be helping researchers find the most effective ways to manage the symptoms and impact of scleroderma and Raynaud’s – not just for today, but for the future too.”
  13. Hit Hard and Early. The Effect of High Dose Methylprednisolone on Nailfold Capillary Changes and Biomarkers in Early Systemic Sclerosis: a 12‑week Randomised Explorative Double‑blind Placebo‑controlled Trial: ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03059979?viewType=Table“This is a 12 week double-blind randomized placebo controlled trial in which 30 patients with very early SSc, fulfilling the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) criteria (9) will be randomized in a 2:1 fashion to receive intravenous methylprednisolone or placebo.”
  14. Clinical Trials and Observational Studies: Johns Hopkins Scleroderma Center https://www.hopkinsscleroderma.org/research/clinical-trials/“Utility of Intensive Cancer Screening Strategies in High Risk Scleroderma Patients. This study is testing whether breast MRI and whole body PET/CT scans improve cancer detection in patients who have had scleroderma for less than 3 years and who are positive for an autoantibody associated with increased cancer risk.”
  15. Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY): ClinicalTrials.gov https://www.guidelinecentral.com/insights/may-2025-scleroderma-trials-rundown/“The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic sclerosis.”
  16. Systemic Sclerosis’ Relatives Reflex (RelativReflex): ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04917146“The main purpose of this pilot study is to better understand the particularities of relatives (caregivers) of patients suffering from systemic sclerosis and will allow us to refine our knowledge about the assistance they provide for SSc patients and its impact on family caregivers.”
  17. Clinical trials: Scleroderma & Raynaud’s UK (SRUK) https://www.sruk.co.uk/research/taking-part-in-research/clinical-trials/“By taking part in or supporting clinical trials, you’ll be helping researchers find the most effective ways to manage the symptoms and impact of scleroderma and Raynaud’s – not just for today, but for the future too.”
  18. Hospital for Special Surgery, “New Research Sheds Light on Why Scleroderma Affects Mostly Women and How to Treat It,”: HSS News https://news.hss.edu/new-research-sheds-light-on-why-scleroderma-affects-mostly-women-and-how-to-treat-it/“Women are four times more likely than men to be diagnosed with the disease.”
  19. Diffuse cutaneous systemic sclerosis. Genetic and Rare Diseases Information Center (GARD) https://rarediseases.info.nih.gov/diseases/9751/diffuse-cutaneous-systemic-sclerosis“Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of systemic scleroderma (systemic sclerosis) and is characterized by skin hardening (fibrosis) and problems in many organs of the body.”
  20. One Step Closer to Achieving Gender Representation in Clinical Trials: JAMA Network Open https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2840283“For decades, clinical trials predominantly composed of men.”
  21. Underrepresentation of women in randomised controlled trials: a systematic review and meta-analysis. Trials journal (PMC) https://pmc.ncbi.nlm.nih.gov/articles/PMC9768985/“The overall median enrollment rate of women was 41% (IQR 27 to 54).”
  22. Fostering diversity in clinical trials: need for evidence and implementation to improve representation: BMJ Medicine https://bmjmedicine.bmj.com/content/3/1/e000984“The lack of diversity in clinical trials undermines the generalisability, quality, and external validity of medical research.”
  23. Racial differences in systemic sclerosis disease presentation: a EUSTAR study. Rheumatology (Oxford) https://academic.oup.com/rheumatology/article/59/7/1684/5611468“Racial factors play a significant role in SSc.”
  24. Ethnic variations in systemic sclerosis disease manifestations, internal organ involvement, and mortality: The Journal of Rheumatology https://www.jrheum.org/content/early/2019/02/25/jrheum.180042“There were 1005 subjects evaluated, the majority of whom were European-descent white (n = 745, 74%), Afro-Caribbean (n = 58, 6%), South Asian (n = 70, 7%), and East Asian (n = 80, 8%). Compared to European-descent white subjects, East Asians less frequently had calcinosis (29% vs 9%, p = 0.002) and esophageal dysmotility (88% vs 69%, p = 0.002); Afro-Caribbeans more frequently had interstitial lung disease (31% vs 53%, p = 0.007); and First Nations subjects more frequently had diffuse cutaneous disease (35% vs 56%, p = 0.02) and diabetes (5% vs 33%, p = 0.03). We found no difference in the short-term survival across ethnicities. Hispanic subjects have better longterm survival (81.3%, 95% CI 63–100) compared to European-descent white subjects (55%, 95% CI 51–60). East Asians appear to have the longest median survival time (43.3 yrs) and Arabs the shortest median survival time (15 yrs). There was no significant difference in median survival times between Afro-Caribbean and European-descent white subjects (22.2 vs 22.6 yrs).”
  25. Randomised controlled trial participants – diversity data report: National Institute for Health and Care Research (NIHR) https://www.nihr.ac.uk/about-us/who-we-are/research-inclusion/randomised-controlled-trial-participants-diversity-data-report“To benefit the NHS, public health and social care, research we fund needs to be widely applicable. And this means the people involved in health and care research need to be diverse.”