Treatment for Systemic Sclerosis Well Tolerated by Patients in Initial Studies

Newswise — A new antibody, still under development, that neutralizes transforming growth factor, TGF beta 1, in patients with diffuse cutaneous systemic sclerosis has proven to be well tolerated for the patients who participated in a recent trial, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Antonio, Texas.

Overactivity of TGF beta 1 is implicated as a key driver of fibrosis or scarring in many conditions including systemic sclerosis. This chronic rheumatic disease, which causes degenerative changes and scarring in the skin, joints and internal organs, affects approximately one to two individuals in every 10,000, predominantly women (female: male = 4:1) between the ages of 30 and 60 years. Those affected experience skin tightness, Raynaud's phenomenon, painful joints and, early in the disease, difficulties in swallowing and gastro-oesophageal reflux.

To study patient tolerance to the future use of CAT-192, an antibody designed to neutralize TGF beta 1 and therefore reduce fibrosis, researchers conducted a trial on 45 subjects enrolled in 11 centers in the U.S. and Europe. The patients, all of whom had contracted systemic sclerosis within the past 18 months, were randomly allocated to one of three doses of CAT-192: 10mg/kg, 5mg/kg, 0.5mg/kg or a placebo given by injection on the first day of the study and in weeks six, 12 and 18. Patients were monitored primarily for safety and bodily absorption, distribution, metabolism and excretion of the drug; and secondarily for skin thickness and hardness, overall health assessment, organ-based disease and laboratory test results.

At the end of the study, there was no significant difference in the safety profiles among the different treatment groups. A total of 275 adverse events occurred in 42 of the participants and, of the 13 patients who experienced serious adverse events, two were on placebo. No secondary outcome showed significant change in any of the four treatment groups.

Results indicate that use of CAT 192 in patients with diffuse cutaneous systemic sclerosis was well tolerated in the patients who participated in the trial. In addition, no safety issues were identified in this study. This trial was not powered to determine the efficacy of treatment. No conclusions about the effectiveness of CAT 192 as a therapy can therefore be made at this stage.

"Showing that repeated treatment with an antibody to TGF beta 1 appears to be safe in systemic sclerosis is an important first step in the development of treatments that could inhibit this protein in diseases in which overactivity is implicated as a key driver," said Christopher P. Denton, MD , PhD, Centre for Rheumatology, Royal Free Hospital, London, England, and an investigator in the study.

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.