Tuesday, 31 Mar 2020

You are here

Fresolimumab (anti-TGF beta) Improves Systemic Sclerosis

Transforming growth factor (TGF-β) is known to have potent profibrotic activity and has been implicated in the pathogenesis of systemic sclerosis a futile condition with no effective disease modifying treatments. The role of TGF-β in SSc, was put to the test in a trial of 15 SSc patients (with a mean disease duration of 8 months) who were treated with 2 different dosing regimens of fresolimumab (an IgG4 κ monoclonal antibody capable of neutralizing TGF-β).  

Patients received either two doses of 1 mg/kg 4 weeks apart (n=7) or one 5 mg/kg dose (n=8) and were assessed at baseline, weeks 3 or 4, 7, and 24 weeks with modified Rodnan skin scores (mRSS), serial skin biopsies, biomarkers and microarrays.  Among the 11 females and 4 males, 60% had digital ulcers, 93% were ANA+, 27% were SCL-70 Ab positive and they had a mean mRSS of 26.9. Only one patient had pulmonary fibrosis.

Rice and coworkers reported that nearly all patients showed a rapid, significant decrease in skin scores, Expression of the biomarkers thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) rapidly declined at one month and week 7. Skin scores began to reverse after week 11 but COMP and THBS1 expression lagged behind, suggesting repeat dosing may be needed in the future.  

Nevertheless, strong correlations were seen between biopsy site (forearm) scores, mRSS, COMP and THBS1.  When compared to other trials, the degree and rapidity of mRSS improvement suggest these changes were more than the natural regression of skin scores in SSc. This this open-label pilot trial, using a first in class inhibitor of TGF-β, has shown significant clinical and biologic effects in patients with diffuse scleroderma.

Thanks to Dr. Barry Gruber of Long Island for identifying this citation.

The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

In Lupus, Keep BP Below 130/80

Blood pressure should be maintained at a level below 130/80 mm Hg in all patients with lupus to lessen their likelihood of atherosclerotic vascular events, Canadian researchers asserted.

In Vasculitis, Beware of Infection

Risks of infection were strikingly high among patients with antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis, which may relate to both the disease and its treatment, Scottish researchers found.

Malignancies with Giant Cell Arteritis

The Journal of Rheumatology reports the findings of a Swedish population-based cohort study of biopsy-proven giant cell arteritis (GCA) patients showing that the overall risk for cancer was not increased; yet there appears to be an increased risk for leukemia and a decreased risk for breast and upper gastrointestinal tract cancers.   

Hospitalized GPA - Higher morbidity, Mortality and Cost

Rheumatology reports on a study of patients with granulomatosis with polyangiitis (GPA) showing worse outcomes and higher costs when hospitalized with GPA.

GPA patients were identified from the Nationwide Inpatient Sample (NIS) and were compared to those without GPA with regard to demographics, procedures, length of stay, mortality, morbidity and total hospitalization charges (between 2005–2014).

Don't Blame the Weather in Sjogren's

Seasonal variations in symptoms -- commonly reported by patients with rheumatic diseases -- were not observed in a large cohort of patients with primary Sjogren's syndrome, French investigators found.