News for Patients


Adempas PAH Benefits Extend to SSc

Author: Nancy Walsh
Date Published: July-2016
Source: MedPage Today

Treatment with riociguat (Adempas) increased exercise capacity among patients whose pulmonary arterial hypertension was associated with connective tissue disease (PAH-CTD) in a post-hoc analysis of a phase III clinical trial, researchers reported.

Among PAH-CTD patients randomized to receive riociguat in dosages up to 2.5 mg three times per day, the mean 6-minute walking distance increased by 18 meters at week 12 compared with a decrease of 8 m (about 26 ft.) for those given placebo, for a mean treatment difference of +28 m (95% CI -4 to 61), according to Christopher P. Denton, MD, of University College London, and colleagues.

 

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial

Author: D.P. Tashkin, MD, M.D. Roth, MD, P.J. Clements, MD, D.E. Furst, MD, D. Khanna, MD, E.C. Kleerup, MD, J. Goldin, MD, E. Arriola, PharmD, E.R. Volkmann, MD, et al
Date Published: July-2016
Source: The Lancet

12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide.

 

Hand Impairment in Systemic Sclerosis: Various Manifestations and Currently Available Treatment

Author: Amber Young, Rajaie Namas, Carole Dodge, Dinesh Khanna
Date Published: July-2016
Source: Springer Link

Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud’s phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often coexist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life. However, despite this knowledge, most diagnostic and treatment principles in SSc are focused on visceral manifestations due to known associations with morbidity and mortality. Treatment of inflammatory arthritis is symptom based and involves corticosteroids ≤10 mg daily, methotrexate, tumor necrosis factor inhibitors, tocilizumab, and abatacept. Small joint contractures are managed by principles of occupational hand therapy and rarely surgical procedures.

 

Advanced Echo Detection of Heart Disease in Scleroderma

Author: Johns Hopkins Rheumatology
Date Published: July-2016
Source: Johns Hopkins Medicine

A new imaging technique reveals evidence of heart dysfunction in Scleroderma patients with undiagnosed heart disease. In a team effort between the Johns Hopkins Divisions of Rheumatology, Cardiology, and Pulmonary/Critical Care Medicine, led by Monica Mukherjee, M.D. and Ami A. Shah, M.D., researchers coupled traditional echocardiography (echo) with a new technique called “speckle-tracking” to reveal the presence of right heart dysfunction that was not detected by traditional methods. This new method may identify patients with Scleroderma who are at high risk for developing disability and even death due to severe heart disease.

 

Taking it personally, cutting-edge biotech snags $45 million

Author: Ron Leuty
Date Published: July-2016
Source: San Francisco Business Times

This year-old company is taking on fibrotic diseases — and it's a personal battle.

 

Digital ulcers in systemic sclerosis

Author: Christopher P. Denton
Date Published: July-2016
Source: The Lancet

Systemic sclerosis (scleroderma) is one of the most recalcitrant of the immune-mediated rheumatic diseases because of its clinical impact and the high mortality associated with the internal organ complications that it causes.1 Lung fibrosis has emerged as a major cause of scleroderma-related death, and with better treatments for pulmonary arterial hypertension, the other main lethal lung manifestation of scleroderma, this looks set to continue.

 

Systemic sclerosis: The need for structured care

Author: Kathleen Morrisroe, Tracy Frech, Janine Schniering, Britta Maurer, Mandana Nikpour
Date Published: July-2016
Source: Clinical Rheumatology

Autoimmune connective tissue diseases (CTDs) have a propensity to affect multiple organ systems as well as physical function, quality of life, and survival. Their clinical heterogeneity, multisystem involvement, and low worldwide prevalence present challenges for researchers to establish a study design to help better understand the course and outcomes of CTDs.

Systemic sclerosis (SSc) is a notable example of a CTD, wherein longitudinal cohort studies (LCS) have enabled us to elucidate disease manifestations, disease course, and risk and prognostic factors for clinically important outcomes, by embedding research in clinical practice. Nevertheless, further efforts are needed to better understand SSc especially with regard to recognizing organ involvement early, developing new therapies, optimizing the use of existing therapies, and defining treatment targets.

 

Raynaud’s Symptoms in SSc Seen to Ease with Iloprost and Bosentan Treatment

Author: Magdalena Kegel
Date Published: July-2016
Source: Scleroderma News

Iloprost (brand name, Ventavis) in combination with bosentan (Tracleer) can improve blood flow in microscopic vessels called capillaries in the hands and feet of patients with systemic sclerosis, where poor capillary function often gives rise to Raynaud’s phenomenon.

The study, “Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis,“ recently published in the journal Modern Rheumatology, inspected capillaries at the nail fold of the finger using video microscopy to evaluate if the two drugs improve the workings of these blood vessels, potentially easing Raynaud’s symptoms.

 

Actelion initiates Phase III study to evaluate macitentan (Opsumit) in children with PAH

Author: Magdalena Kegel
Date Published: July-2016
Source: Scleroderma News

Actelion Ltd (ATLN.VX) announced today that it will be initiating a Phase III study to evaluate the effect of macitentan on delaying disease progression in children with PAH using a pediatric formulation of macitentan (Opsumit).

TOMORROW (pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide) is a multicenter, controlled, randomized, open-label event-driven study to assess the efficacy, safety and pharmacokinetics of macitentan versus standard of care in children with PAH.

 

 

Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort

Author: Daniel Rosenberg, Barbara Schwierin and Marco Matucci-Cerinic Yannick Allanore, Christopher P Denton, Thomas Krieg, Peter Cornelisse
Date Published: June-2016
Source: Annals of the Rheumatic Diseases

Digital vasculopathy in systemic sclerosis (SSc) consists of a spectrum of Raynaud’s phenomenon (RP), digital ulcers (DUs), critical digital ischaemia and escalation to gangrene. The complications of severe digital vasculopathy often require hospital-based management with intravenous therapies and surgery.1–3 Although gangrene is not infrequent in the clinic, data on the prevalence and implications of gangrene in patients with SSc are scarce.

 

Actemra may reduce scleroderma skin thickening

Author: Ara Freeman
Date Published: June-2016
Source: Dermatology News Digital Network

The interleukin-6 inhibitor tocilizumab (Actemra) substantially reduced skin thickening in patients with systemic sclerosis in the “proof-of concept” faSScinate trial, the results of which have now been published in the Lancet. The mean change in the primary endpoint of a modified Rodnan skin score at 24 weeks was –3.92 in the tocilizumab group and –1.22 in the placebo group, with an overall difference of –2.70 (95% confidence interval, –5.85-0.45; P = .0915). The effect was sustained at 48 weeks’ follow-up (–6.33 vs. –2.77; 95% CI, –7.2-0.12; P = .0579).

 

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

Author: Dinesh Khanna, Carlo Albera, Aryeh Fischer, Nader Khalidi, Ganesh Raghu, Lorinda Chung, Dan Chen, Elena Schiopu, Margit Tagliaferri, James R. Seiboldand Eduard Gorina
Date Published: June-2016
Source: The Journal of Rheumatology

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc.

 

iBio’s Endostatin-Related Peptides for Fibrosis, Scleroderma Issued US Patent

Author: Magdalena Kegel
Date Published: June-2016
Source: Scleroderma News

The pharmaceutical company iBio, which focuses on the clinical development of drugs for systemic sclerosis and other fibrotic diseases, was recently issued a U.S. patent protecting the company’s drug development attempts using endostatin-related peptides for the treatment of fibrosis.

According to a press release, the patent, US 9,365,616, titled “Use of Endostatin Peptides for the Treatment of Fibrosis,” complements earlier U.S. patents 8,507,441 and 8,716,232 covering this line of drug development. The patent covers both the composition of the drugs and the methods for which endostatin-related peptides might be used.

 

Potential beneficial role for endothelin in scleroderma vasculopathy: inhibition of endothelial apoptosis by type B endothelin-receptor signaling

Author: Yongqing Wang, Nezam Altorok, Bashar Kahaleh
Date Published: June-2016
Source: Scleroderma Journal

Microvascular endothelial cell (MVEC) apoptosis is considered to be a key event in the pathogenesis of systemic sclerosis (SSc), an increased expression of endothelin-1 (ET1) is also well recognized in the disease. ET1 is thought to exert deleterious effects on the vasculature by virtue of its known vasospastic, proliferative and fibrotic effects, yet ET1 can act as a survival factor for a variety of cells, including MVEC. The aim of this study is to investigate if ET1 signaling protects SSc-MVECs from apoptosis.

 

Being Disfigured by Scleroderma Gave Me the Chance to Love Myself

Author: Lisa Goodman-Helfand
Date Published: June-2016
Source: Dr. Oz, The Good Life

Nobody escapes adolescence unscarred by the agony of bullies, peer pressure, acne, and hormones. Along with every survivor of that awkward era, I, too, faced these obstacles. But I had the added bonus of navigating a newly diagnosed autoimmune disease: scleroderma.

I was 10 years old when doctors introduced me to the unknown world of scleroderma. It was 1985, long before Google could tell you every horrifying detail about your illness. I had no idea scleroderma could affect a patient externally, causing the skin to tighten and result in disfigurement and other painful physical abnormalities. Nor did I know that in its worst form, scleroderma attacks one's internal organs and can be fatal. In an effort to shield me from the complexities of scleroderma, my mom told me that my skin was tighter than normal, but that I was perfectly fine otherwise.

 

Scleroderma Patients and Lung Transplantation

Author: John Hansen-Flaschen, MD
Date Published: June-2016
Source: ATS News

Two studies published in the June issue of Annals of the American Thoracic Society look at scleroderma and lung transplantation. Patients with advanced lung disease due to systemic sclerosis (SSC) have long been considered poor candidates for lung transplantation. However, in a retrospective study of lung transplant outcomes over an eight-year period at the University of Pittsburgh, Maria M. Crespo. MD, and colleagues found that one- and five-year survival in patients with scleroderma are similar to pulmonary fibrosis. The results, they wrote, “indicate that lung transplant is a reasonable treatment option in selected patients with scleroderma.”

 

Phase 3 Trial to Begin for Terguride in Diffuse Cutaneous Scleroderma

Author: Magdalena Kegel
Date Published: June-2016
Source: Scleroderma News

The German pharmaceutical company Medac, in August, will begin Phase 3 of a clinical trial to access the therapeutic potential of terguride, a disease-modifying drug for the treatment of diffuse cutaneous systemic sclerosis.

Terguride is a serotonin receptor blocker, acting at two particular serotonin receptors called 5-HT2A and 5-HT2B. Medac is convinced that stopping the nerve signaling in serotonin neurons will block the progression of fibrotic tissue development and blood vessel remodeling in organs affected by diffuse cutaneous systemic sclerosis.

 

Pfizer, Novartis, BMS join $45M round for early fibrotic disease startup

Author: Stacy Lawrence
Date Published: June-2016
Source: Fierce Biotech

A trio of pharmas have bought into the early vision of startup Blade Therapeutics. Pfizer Venture Investments, Novartis Institutes for Biomedical Research and Bristol-Myers Squibb ($BMY) all came in to the $45 million Series B round for the startup, which aims to address novel targets in fibrotic disease. It expects to get into the clinic with this financing.

Founded in the fall of 2015, Blade is based upon technology in-licensed from Johns Hopkins University, in particular, on work from the lab of Dr. Harry Dietz--a professor of genetics and medicine at the university and the company’s founder. His work focuses on the cause of a pair of fibrotic diseases: Marfan Syndrome and Stiff Skin Syndrome, which forms the basis of Blade’s investigation into new biological pathways involved in tissue fibrosis and dysfunction.

 

Progression of Lung Fibrosis in Scleroderma May Be Predicted by Antibody-Specific T-cells

Author: Magdalena Kegel
Date Published: May-2016
Source: Scleroderma News

Immune T-cells induced by the presence of autoantibodies against topoisomerase-I were linked to lung fibrosis and found to predict disease progression in scleroderma patients. The finding may open new avenues of research into treatments that selectively target the various tissue-specific disease manifestations of scleroderma — a substantial improvement to the nonselective immunosuppression used today.

In scleroderma, autoantibodies targeting specific structures are linked to various clinical representations of the disease. One such antibody against the enzyme topoisomerase-I, crucial for the winding and unwinding of DNA molecules during gene expression and cell divisions, is present in 20 percent to 45 percent of scleroderma patients and linked to diffuse skin disease and lung fibrosis. Patients with anti-topoisomerase-I antibodies also have more severe disease.

 

Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial

Author: H. Ghofrani, F. Grimminger, E. Grünig, Y. Huang, et al
Date Published: April-2016
Source: The Lancet

Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment.