Top 10 Scleroderma Stories of 2018

Throughout 2018, Scleroderma News provided daily coverage of treatment developments, clinical trials, risk factors, and non-pharmacological approaches related to scleroderma.

As we look forward to reporting more news to patients, family members, and caregivers dealing with the disease in 2019, here are the 10 most-read articles of 2018, with a brief description of their relevance to the scleroderma community.

No. 10 — “#EULAR2018 – Lenabasum Safe and Effective in Diffuse Scleroderma Patients, One-year Trial Data Show”

A long-term extension of a Phase 2 trial (NCT02465437) showed that one year of treatment with twice-daily lenabasum (20 mg), an investigational treatment developed by Corbus Pharmaceuticals for patients with diffuse cutaneous scleroderma, was safe, well-tolerated, and led to lower scores on disease state and organ damage. In addition, skin thickness and itchy sensations were reduced, while results of global health assessments also showed improvements. Lenabasum is intended to block both pro-inflammatory and pro-fibrotic (scarring) signals by binding to the cannabinoid receptor type 2 (CB2) in activated immune cells and fibroblasts. An international Phase 3 trial (NCT03398837), called RESOLVE-1, is currently recruiting participants.

No. 9 — “Use Immunosuppressants Cautiously in Scleroderma-linked Lung Disease, Study Advises”

A large European study in adults with interstitial lung disease (ILD) associated with scleroderma showed that immunosuppressive therapy should be used carefully and under close monitoring. The results revealed that patients who had received stand-alone or combination immunosuppressive therapy had more severe and active ILD, as well as worse lung function, compared with those who had not. In particular, patients treated with cyclophosphamide had the most severe disease, the worst lung function, and severe skin fibrosis. This finding was in contrast to treatment with methotrexate, which was associated with the best lung function, lowest prevalence of pulmonary hypertension, and shorter disease duration.

No. 8 — “Silica Dust Exposure Linked to Higher Prevalence of Certain Systemic Sclerosis Manifestations, Study Shows”

Inhalation of silica — a naturally found mixture of silicon with two oxygen atoms — is associated with a higher prevalence of diffuse cutaneous scleroderma, along with muscle inflammation and lung scarring. Such was the main finding of a study in 80 scleroderma patients living in the Italian province of Modena, which has a high density of industries and high risk of silica dust inhalation. Exposure to silica dust preceded disease onset. Additionally, abnormally high blood values of worse prognosis markers — C-reactive protein, anti-Scl70 antibodies, and erythrocyte sedimentation rate — correlated with higher levels of silicon.

No. 7 — “Fibrocell Can Begin Clinical Trials of Scleroderma Therapy FCX-013”

In March, we reported that the U.S. Food and Drug Administration allowed Fibrocell Science to start clinical trials testing FCX-013, a gene therapy candidate for moderate to severe localized scleroderma. FCX-013 uses engineered fibroblasts to produce a protein called matrix metalloproteinase 1 (MMP-1), implicated in breaking down collagen, the excessive production of which is a hallmark of scleroderma. The investigational treatment is administered under the skin. MMP-1 production only occurs when patients also take a compound called veledimex, which enables tight control over when this key protein is produced. A Phase 1/2 trial of FCX-013 in this patient population (NCT03740724) — first with adults, then also with children — is currently enrolling participants. The FDA recently granted fast track designation to FCX-013.

No. 6 — “Fat Tissue Cell Therapy Improves Scleroderma Patients’ Hand Function, Trial Shows”

A clinical trial called STAR (NCT02396238) found that implanting some of scleroderma patients’ fat, or adipose, cells under the skin of their fingers improved hand function and overall disability. Cytori Therapeutics’ Habeo cell therapy collects adipose-derived regenerative cells, which have stem cell properties. This approach avoids tissue rejection and spares patients from taking immunosuppressants. The trial revealed the cell therapy improved hand function of 52% of the treated patients after 48 weeks, compared with 16% of those receiving placebo. An overall decrease in disability was especially evident in measurements such as eating and gripping. The cell therapy was safer than placebo, and also led to greater quality of life and lower disease activity.

No. 5 — “Nailfold Capillary Damage a Mortality Predictor in Scleroderma, Study Shows”

Using a widely used technique in the diagnosis of scleroderma called nailfold capillaroscopy, a team from Australia found that nailfold capillary damage is a predictor of mortality in scleroderma patients. The research included 150 patients with either limited, diffuse, or overlap scleroderma, depending on the extent of skin involvement. Patients with the diffuse subtype had significantly greater areas without capillaries, or capillary dropout, later found to be linked with shorter survival. Links between capillary damage and anti-RNAP3 or anti-Scl70 autoantibodies (those targeting the body’s own tissues) were also reported.

No. 4 — “Raynaud’s Association Campaign Aims to Raise Awareness About Disease’s Pain”

In October, which was Raynaud’s Awareness Month, we reported on the Raynaud’s Association’s campaign “Don’t Turn a Cold Shoulder to Painful Fingers” to raise awareness about the pain experienced by patients with Raynaud’s phenomenon. The association invites patients to share their stories via the campaign’s website or the association’s Facebook page. Raynaud’s may be linked with scleroderma and other illnesses, and can cause great discomfort and pain. Patients often face frequent challenges, as doctors, family and friends may dismiss the effects of pain. Most patients also do not seek treatment, which precludes early detection of diseases possibly associated with the condition. The association launched an interactive multichannel news release for the Raynaud’s community, including educational materials and a list of potentially beneficial products.

No. 3 — “Lenabasum Continues to Show Promise for Treatment of Systemic Sclerosis in Extension Study”

Our third most-read article in 2018 provided updated findings from a Phase 2 trial with lenabasum. Specifically, the therapy was shown to ease inflammation in 38% of patients and fibrosis in 43% of patients, which contrasted to only 15% of placebo-treated patients showing such improvements. In line with previously reported results, the therapy led to a 92% improvement in the mean CRISS score, a measure of disease state and organ damage, reduced skin thickness and itchy sensations, and enabled stable lung function. No serious treatment-related adverse events were reported in this open-label extension study.

No. 2 — “Cannabinoid-derived Therapies Slow Fibrosis, Block Inflammation in Scleroderma, Mouse Studies Show”

Two compounds derived from cannabidiol — a natural chemical extracted from the cannabis plant — eased skin and lung fibrosis in a mouse model of scleroderma. Emerald Health’s oral compounds, EHP-101 and VCE-004.3, activate the PPAR-gamma and CB2 receptors, regarded as promising targets to prevent inflammation and fibrosis. Besides lessening fibrosis and normalizing the activity of fibrosis markers, EHP-101 also inhibited the accumulation of collagen, halted signaling via the scleroderma driver TGF-beta, and reduced the infiltration of inflammatory cells. VCE-004.3, which also blocks the CB1 receptor, inhibited collagen production and prevented the transformation of TGF-beta-induced conversion of fibroblasts into collagen-forming myofibroblasts. Similar to EHP-101, this compound decreased the activity of inflammatory and profibrotic factors.

No. 1 — “Arm Exercises May Enhance Blood Circulation in Scleroderma Patients, Study Suggests”

The most-read article of 2018 reported results of a clinical study (NCT03058887) showing that high-intensity arm exercises, or arm cranking, may improve blood circulation in patients with scleroderma. This benefit results from dilating blood vessels (vasodilation) and increasing the amount of oxygen consumed in the muscles. Exercising the legs through cycling was not as effective for vasodilation. The study included 34 patients with limited cutaneous scleroderma. Those in the arm cranking and cycling groups underwent 12-week, twice-weekly programs. Though both programs improved life satisfaction and reduced Raynaud’s-associated pain and discomfort, patients tended to prefer the arm cranking exercise.

At Scleroderma News, we hope these stories and our reporting throughout 2019 contribute to informing and improving the lives of everyone affected by the disease.

We wish all our readers a happy 2019.