Glivec (imatinib mesylate) in systemic sclerosis, a pilot study

Systemic sclerosis is a debilitating generalized autoimmune disorder,
characterized by fibrotic arteriosclerosis of peripheral and visceral
vasculature and variable degrees of extracellular matrix accumulation (mainly
collagen) in both skin and viscera. The disease is associated with specific
autoantibodies. Various subsets of disease with specific clinical features and
variable involvement of internal organs are distinguished.
Involvement of internal organs, including gastrointestinal tract, lungs, heart
and kidneys, accounts for increased morbidity and mortality. No putative
antifibrotic or immunosuppressive agents have yet been shown to be of
unequivocal benefit in placebo-controlled clinical trial. Treatment is for
mostly supportive.
Due to its extensive proliferation and increased collagen synthesis the
fibroblast is regarded as the key effector cell in fibrosis. A host of
mediators has been implicated in the pathogenesis of fibrosis. Platelet derived
growth factor (PDGF) is regarded as a key molecule driving the fibrotic
response. Therefore the PDGF pathway may be considered an attractive pathway
for pharmacological intervention of the fibrotic response in these patients.
PDGF-receptors belong to the so-called receptor tyrosine kinase family.
Recently, several compounds have been developed that block signal transduction
of various tyrosine kinases. In the present study we would like to examine
whether the tyrosine kinase inhibitor Glivec is capable of inhibiting disease
progression patients with systemic sclerosis.

To investigate the efficacy (and the toxicity) of Glivec in systemic sclerosis
by examining clinical outcomes (clinical and laboratory findings).

Open label study. Purpose evaluation of effect on skin score, digital ulcers,
pulmonary and renal function.
Planned treatment: Glivec 1 dd 400 mg
Treatment duration: 12 months

Glivec 1 dd 400 mg

Treatment with Glivec has adverse effects.The presence of adverse effects will
be actively sought and will be recorded on standardised forms. Adverse effects
sufficient to withdraw medication will be determined after discussion with the
trial coordinator (PvD). Intolerance to Glivec is an end-point of the study and
will result in departure from the protocol without withdrawing the patient from
the study.