Smoking, higher BMI linked to more fatigue; older age, being male to less
by Andrea Lobo, PhD | December 3, 2024

​Fatigue levels in people with scleroderma, also known as systemic sclerosis or SSc, are tied to several social, demographic, lifestyle, and disease-related factors, according to a study by a multinational team of researchers.

Smoking, higher body mass index (BMI) -- a measure of body fat based on height and weight -- pain, gastrointestinal involvement, and lung disease were among the factors associated with more fatigue. In contrast, older age and male sex were linked to lower fatigue scores.

“Some factors that we have identified may be modifiable using generic interventions, including BMI and current smoking; as with any patients, people with SSc should be advised and supported to maintain a healthy lifestyle,” the researchers wrote, noting, however, that “in people with SSc, fatigue scores were substantially higher than in the general population.”

The team also called on clinicians to focus on pain when treating scleroderma patients, and seek ways to lessen its impact.

“Given the substantial association of pain with fatigue in our study, healthcare professionals should work with patients to identify aspects of [the] disease that are causing pain and attempt to address them,” the researchers wrote.
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The study, “Fatigue levels and associated factors in systemic sclerosis: a cross-sectional study of 2385 SPIN Cohort participants,” was published in the journal Rheumatology.

Therapy also being developed for other autoimmune diseases, cancer by Steve Bryson, PhD | November 26, 2024

​Soquelitinib, Corvus Pharmaceuticals’ immune-modulating investigational oral treatment for autoimmune diseases and certain cancers, reduced the signs and symptoms of lung disease caused by systemic sclerosis (SSc), according to new preclinical data.

Designed to selectively block ITK, an enzyme predominantly found in immune T-cells, soquelitinib suppresses Th2 cells — a type of immune helper T-cells whose activation drives the development of many autoimmune and allergic diseases. At the same time, ITK inhibition promotes the growth of Th1-type helper T-cells, which are required for immunity to infections and tumors.

The treatment’s goal is to prevent lung damage, inflammation, and high blood pressure related to SSc. It’s also being investigated in other autoimmune diseases and cancers associated with T-cells.

“We continue to build evidence that selective ITK inhibition can modulate immune responses for a wide range of immune diseases,” Richard A. Miller, MD, co-founder, president, and CEO of Corvus, said in a company press release.
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Yannick Allanore, MD, PhD, a professor of rheumatology at Université Paris Cité in France, presented the preclinical data as a poster at the American College of Rheumatology Convergence 2024, held in earlier this month in Washington, D.C.

Researchers sequence lung fibroblasts to test hypothesis by Steve Bryson, PhD | November 19, 2024

​Cells derived from people with systemic sclerosis (SSc) had widespread DNA mutations compared with healthy cells, which may explain the higher risk of cancer in this patient population, according to a study.

Changes included mutational patterns found solely in the genomes of certain cancers, as well as changes in one or two DNA building blocks, insertions and deletions of DNA segments, and alterations in whole chromosomes.

The study, “Widespread mutagenesis and chromosomal instability shape somatic genomes in systemic sclerosis,” was published in Nature Communications.

SSc, or scleroderma, is an autoimmune disorder that affects the skin and connective tissue. It’s marked by the build-up of scar tissue in the skin and potentially various organs, including the heart and blood vessels, as well as the lungs, stomach, and kidneys.
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Studies suggest that the incidence of cancer in people with SSc is higher than in the general population, with up to about one in five patients developing cancer. Because the abnormal immune response in SSc can damage a wide range of tissues, it’s been suspected that this damage may extend to DNA, thus giving rise to cancer-causing mutations.

Certain autoantibodies tied to lungs and kidneys, study finds by Andrea Lobo, PhD | November 12, 2024

The specific self-reactive antibodies (autoantibodies) of people with systemic sclerosis (SSc) overlap syndrome — a condition in which SSc patients have clinical signs and autoantibodies related to other connective tissue diseases — are tied to organ damage and SSc prognosis, according to a single-center study in China.

Patients with anti-Scl-70 antibodies were more likely to have lung and kidney involvement, while anti-centromere antibodies (ACA) were tied to a lower risk of lung involvement, the study found.

“Rheumatologists may pay more attention on autoantibodies in the clinical practice, so as to provide evidence for further accurate disease assessment and treatment,” the researchers wrote.
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The study, “Autoantibodies in systemic sclerosis overlap syndrome and their correlation with organ damage and survival,” was published in Rheumatology.
SSc is an autoimmune disease characterized by the accumulation of scar tissue in the skin and potentially internal organs, including the heart, kidney, lungs, and digestive tract. SSc overlap syndrome patients have clinical features or autoantibodies related to connective tissue disorders such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) — the most common form of lupus — and Sjögren’s disease.

Developer planning to launch Phase 2 trials in fibrotic diseases in 2025
by Patricia Inácio, PhD | October 29, 2024

CAL101, a therapy candidate for fibrosis (scarring) in scleroderma and related disorders, was found to be safe and well tolerated in a Phase 1 clinical trial, according to new data from the study.

Developed by Calluna Pharma, CAL101 is a first-in-class antibody that targets S100A4, a protein previously associated with SSc and idiopathic, or of unknown cause, pulmonary fibrosis.

Calluna expects to test the investigational therapy in Phase 2 trials of fibrotic and fibrotic-inflammatory-related disorders in 2025, the company said in a press release.
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“We are encouraged by the findings from the Phase 1 study. These results are an important step forward in the development of our lead asset, CAL101, particularly for fibrotic and fibro-inflammatory diseases where there remains a critical need for innovative therapeutic options,” said Jonas Hallén, MD, PhD, co-founder and chief medical officer of Calluna. “We are excited as we now move into the next phase of clinical development.”

NMR spectroscopy compared fat profiles of SSC, healthy blood samples by Margarida Maia, PhD | October 22, 2024

Low levels of high-density lipoprotein (HDL), the so-called “good” cholesterol, are linked to more severe symptoms of systemic sclerosis (SSc) with interstitial lung disease (ILD), a study finds, suggesting that profiling fats in the blood could aid in planning more personalized treatments for the disease.

The study, “Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with interstitial lung disease,” was published in Respiratory Medicine by researchers in Germany.

In SSc, also called scleroderma, overly active immune cells lead to thickened patches of hardened skin and sometimes to scarring in internal organs. When scarring builds up in the lungs, it can cause ILD, where the air sacs and the tissue around them become damaged, making it difficult to breathe.
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What triggers SSc isn’t clear, but circulating fats such as cholesterol may play a role in how the disease develops. Cholesterol is carried in the bloodstream in particles called lipoproteins. One such lipoprotein, HDL, helps remove unused cholesterol from the body. It also protects small blood vessels from damage and prevents blood clots from forming.

Muscle mass, bone density shown to be significant pretransplant predictors
by Steve Bryson, PhD | October 15, 2024

A chest CT scan taken before a lung transplant can help predict survival after the transplant in people with systemic sclerosis (SSc), a new U.S. study suggests.

Muscle mass, bone density, and the volume of the heart and blood vessels were among the “novel image features” of the pretransplant CT that best predicted a patient’s survival, according to the researchers.

Adding CT data to demographic and clinical characteristics improved the accuracy of survival prediction, but CT scans alone could also accurately predict posttransplant survival, the study found.

“Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis,” the scientists wrote.

Their study, “Predicting post-lung transplant survival in systemic sclerosis using CT-derived features from preoperative chest CT scans,” was published in the journal European Radiology.

Investigating a CT scan of the chest as a possible prediction tool
In SSc, also called scleroderma, a mistaken self-directed immune response drives inflammation and scar tissue buildup, or fibrosis, in the skin and potentially the internal organs.

When the lungs are affected, the scarring makes it more difficult to breathe and can increase the risk of mortality, or death. In severe cases, a lung transplant may be indicated when other therapies have proven to be ineffective.

Lung transplant in SSc accounts for about 0.9% to 1.2% of all lung transplants. This may be due to the disease’s complex, multiorgan nature, which limits the number of clinical centers performing transplants in this patient population.
As such, “there is a pressing need for additional research to understand post-[lung transplant] survival factors and identify those who are suitable for this procedure,” the researchers wrote.
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A CT scan of the chest is routinely performed before a lung transplant to assess the patient’s condition and disease and to monitor the individual’s health status. According to the team, such scans may also contain valuable information that may predict posttransplant complications and survival.

Outcomes differ for patients of different races, meaning antibodies play a role
by Marisa Wexler, MS | September 17, 2024

Some types of disease-specific antibodies are more common in Black patients with scleroderma than white patients, a study shows.

Differences in antibody profiles may help explain why clinical outcomes tend to differ for patients of different races, but the data suggest these variations can’t fully account for all the clinical differences between races, meaning other factors must also factor in.

“Distinct autoantibody types are enriched in Black [scleroderma] patients compared with those observed in white patients; these specificities associate with more aggressive clinical manifestations of the disease. However, differences in autoantibody distributions explain only a fraction of the racial effects on clinical outcomes,” the researchers wrote.

The study, “Racial variability in immune responses only partially explains differential systemic sclerosis disease severity,” was published in the Annals of the Rheumatic Diseases.
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Scleroderma, also called systemic sclerosis, or SSc, is marked by uncontrolled fibrosis (scarring) that can affect various organs. Several specific types of autoantibodies, that is, antibodies that attack healthy tissue and are thought to be a main driver of the disease, have been linked to the disease. The biological consequences of individual autoantibody types are poorly understood, however.

Calcium channel blocker seen to ease SSc symptoms such as Raynaud's
by Margarida Maia, PhD | September 10, 2024

The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Aisa Pharma’s Profervia (cilnidipine), an investigational oral calcium channel blocker also known as AISA-021, for the treatment of systemic sclerosis (SSc).

In its request package for the designation, the company included data from an ongoing Phase 2 clinical study called RECONNOITER (ACTRN12621000459820) in which Profervia is showing benefits in easing symptoms of SSc. Among the symptoms reduced is Raynaud’s phenomenon, which causes pain and tingling in the hands and fingers.

“We hope this designation will accelerate our development program for AISA-021, which is designed to provide a once-daily, well-tolerated, and economical treatment that we hope can improve the lives of patients with SSc,” Andrew Sternlicht, MD, Aisa’s CEO and founder, said in a company press release.
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The granting of orphan drug status provides an incentive for companies to develop products for rare diseases. The designation’s benefits include tax credits and a potential seven years of market exclusivity should the treatment ultimately be approved. According to Sternlicht, the company believes this is “the first time” a calcium channel blocker has been granted such a designation for an autoimmune disease.

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.