Early treatment could benefit at-risk patients, researchers say by Margarida Maia, PhD | August 20, 2024

Long-term treatment with Volibris (ambrisentan), marketed as Letairis in the U.S., may help prevent mild pulmonary vascular disease from developing into pulmonary arterial hypertension (PAH) in people with scleroderma, a study suggested.

“Early treatment and close follow-up could be beneficial in this high-risk group,” wrote the researchers from Germany and the U.K., who collaborated on the EDITA Phase 2 study (NCT02290613) and its long-term follow-up, EDITA-ON.

The study, “Effect of ambrisentan in patients with systemic sclerosis and mild pulmonary arterial hypertension: long-term follow-up data from EDITA study,” was published in Arthritis Research & Therapy.
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Scleroderma, or systemic sclerosis, occurs when the immune system attacks the body’s own healthy tissues, and potentially affects the lungs. This can cause complications such as pulmonary vascular disease, a term for any disease that affects the blood vessels leading to or branching from the lungs.
Patients with pulmonary vascular disease are at risk of developing PAH, which causes high blood pressure in the blood vessels taking blood from the heart to the lungs, making physical activity more difficult.

Therapy particularly effective as add-on treatment by Patricia Inácio, PhD | August 13, 2024

Intravenous immunoglobulin (IVIG) eases skin, muscle and digestive symptoms in people with scleroderma (SSc), particularly when used as an add-on therapy, according to a recent review study.

While no improvements were seen in respiratory function, IVIG still led to stabilization of these symptoms.

The findings “suggest that IVIG may be effective in treating a range of organ-specific manifestations with minimal side effects, thus making it a potentially attractive therapeutic option for SSc,” the researchers wrote.

The review, “Role of intravenous immunoglobulins in systemic sclerosis (SSc): A systematic literature review,” was published in Seminars in Arthritis and Rheumatism.
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Scleroderma, also called systemic sclerosis, is an autoimmune disease that causes the hardening and fibrosis — thickening or scarring — of the skin. Often, scleroderma also affects internal organs, posing a risk of more severe outcomes.

25% of patients saw side effects months after treatment by Patricia Inácio, PhD | August 6, 2024

Scleroderma patients who have cancer may be treated with radiotherapy without a notable risk of skin and pulmonary worsening, a review study suggests, but around 25% of patients saw severe acute and late toxicities, that is, side effects months after radiation therapy.

As such, “individualized assessment, close collaboration between radiation oncologists and rheumatologists, use of high precision radiotherapy techniques to minimize dose to organs at risk, and vigilant monitoring are key to optimizing the risk-benefit balance,” scientists wrote in the review, “Effects of Radiotherapy for Malignancy in Systemic Sclerosis. A Systematic Review,” in The Journal of Rheumatology.

Studies have shown that having scleroderma increases the risk for developing cancer, especially lung, blood and head and neck cancers.

While radiotherapy is a cornerstone of cancer treatment, its use in scleroderma patients has raised concerns about causing severe skin thickening and localized scleroderma in people without prior disease. In fact, the American College of Radiology considers scleroderma and related disorders as contraindications for treatment to remove an area of cancer from the breast.
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Evidence in scleroderma is scarce, however, leading researchers from Canada and Saudi Arabia to review 26 studies published across four databases to better understand safety and outcomes of radiotherapy in scleroderma. Half the studies analyzed were case reports and most were from the U.S. The studies were published between 1987 and 2021, and taken together they reported on 121 scleroderma patients treated with radiotherapy. The patients’ mean age was 56.4 and 83.3% were female.

Analysis IDs over 1,000 genes with different expression vs. controls 
by Patricia Inácio, PhD | July 30, 2024

Cells present along the walls of small blood vessels in the lungs, called pericytes, have distinct gene activity in people with systemic sclerosis (SSc)-associated pulmonary fibrosis (PF), according to a new study.

Pericytes from SSc patients showed an increased expression, or activity, of genes involved in lung fibrosis (scarring), blood vessel formation, and extracellular matrix organization. The extracellular matrix is a network of molecules that maintain cell structure.

The study, “Transcriptomic characterization of lung pericytes in systemic sclerosis-associated pulmonary fibrosis,” was published in the journal iScience.
Pulmonary fibrosis is a type of interstitial lung disease, a group of disorders marked by inflammation and fibrosis. SSc-associated PF is the leading cause of death in SSc patients.

Pericytes are key cells for the maintenance of blood vessels in the lungs. These cells establish communication routes with other cells types, via a direct interaction or the release of growth factors.
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However, the role of pericytes in SSc-PF is still far from understood. Studies have suggested that they may contribute to the transition of fibroblasts into myofibroblasts, a normal process in wound healing. However, the persistent presence of myofibroblasts is key in driving tissue fibrosis.

Designation grants developer 7 years market exclusivity if therapy is approved
by Patricia Inácio, PhD | July 23, 2024

The European Medicines Agency (EMA) has granted orphan drug status to FT011, an oral therapy candidate that Certa Therapeutics is developing for systemic sclerosis (SSc).

The U.S. Food and Drug Administration (FDA) awarded the therapy a similar status last year, followed by fast track designation this year.

Orphan drug status is given by both agencies to medicines designed for the treatment of serious or life-threatening rare diseases — those affecting fewer than five in 10,000 people in the European Union or fewer than 200,000 individuals in the U.S. Among its benefits is a period of marketing exclusivity should the therapy be approved; that period is seven years in the U.S. and 10 years in Europe.

“With limited treatment options available for patients with SSc, the EMA orphan drug designation and FDA orphan drug and fast track designations reflect the potential for FT011 to address a critical need for people living with this debilitating and life-threatening condition,” Darren Kelly, PhD, founder and CEO of Certa, said in a company press release.
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“These are significant validations for the company and highlight the unmet need for novel medicines to reduce inflammation and scarring in chronic fibrotic diseases, which are often progressive and can have a poor prognosis,” Kelly added.