Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Comparative Analysis of Change in Modified Rodnan Skin Score in Patients with Diffuse Systemic Sclerosis Receiving Imatinib Mesylate Suggests Similar Disease Course to Matched Patients Receiving Standard Therapy.

Denton9,  Christopher P., Nihtyanova2,  Svetlana I., Varga5,  John, Distler10,  Oliver, Wigley4,  Fredrick M., Lafyatis1,  Robert A., Distler11,  Jorg H. W.

Boston University School of Medicine, Arlington, MA
University Hospital Zurich, Zurich, Switzerland
University of Erlangen, Erlangen, Germany
University of Florence, Firenze, Italy
Center for Rheumatology and Connective Tissue Diseases, UCL Medical School, London, United Kingdom
Friedrich Alexander Univ, Erlangen, Germany
Johns Hopkins University, Baltimore, MD
Northwestern Univ Feinberg School, Chicago, IL
Novartis Institutes for Biomedical Research, Cambridge, MA
Novartis Institutes for Biomedical Research
Novartis Pharma
Royal Free Hospital, London, United Kingdom

Background and Purpose:

Despite preclinical evidence and anecdotal case reports supporting potential benefit, clinical trials of the selective tyrosine kinase inhibitor imatinib mesylate in systemic sclerosis (SSc) have provided conflicting results with regard to efficacy as assessed by the modified Rodnan Skin score (mRSS). Our aim was to compare the course of mRSS in patients treated with imatinib in a multi-center, open-label, Proof of Concept (PoC) study in diffuse SSc [submitted in parallel to ACR 2010] and in patients receiving standard therapy in a well characterized large single centre cohort.

Methods:

27 cases of diffuse cutaneous SSc were treated with imatinib mesylate in an open-label prospective clinical trial. To develop a comparator cohort to help interpret clinical outcome in this trial, data from a SSc patient database (n>2000) from a large tertiary referral centre for SSc, were analyzed to select dcSSc patients whose main characteristics (disease duration and mRSS at baseline, age, sex, and concomitant diseases) matched those of the patient population in our PoC study. Patients (n=116 selected) in the control group received standard immunomodulatory treatment except for 19 (16 %) patients who received no immunosuppressive treatment. Imatinib was initiated at an oral dose of 200 mg/day for 4 weeks then up-titrated to 400 mg/day for 2 weeks followed by 600 mg/day until Week 24. A data driven descriptive analysis as well as a longitudinal mixed effects model were utilized to compare the changes in mRSS in the imatinib treated group (n=27) and in the control group (n=116).

Results:

In the imatinib group in our PoC study, mean mRSS increased by 9.9 % at Week 24, however, there was a trend towards an improvement in mRSS (-21%) at Week 48, 24 weeks after the end of treatment. As compared to the control group, after an initial increase in mRSS in the imatinib group, the time course of mRSS was similar to that of the control group.

For two patients treated with imatinib who demonstrated a mRSS decrease greater than 25% at week 24, there were matching individuals from the control group with a similar profile.

Conclusions:

Our data suggest that the changes in mRSS after 24 week treatment with imatinib in our PoC study are similar to those observed in cases receiving standard therapy. Such comparative analyses using large databases of well characterized cases may help better interpret results in further Proof of Concept studies of systemic sclerosis where the enrollment of a large number of patients is usually not feasible. Thus we provide a model for future early stage clinical studies in SSc.

To cite this abstract, please use the following information:
Denton, Christopher P., Nihtyanova, Svetlana I., Varga, John, Distler, Oliver, Wigley, Fredrick M., Lafyatis, Robert A., et al; Comparative Analysis of Change in Modified Rodnan Skin Score in Patients with Diffuse Systemic Sclerosis Receiving Imatinib Mesylate Suggests Similar Disease Course to Matched Patients Receiving Standard Therapy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :566
DOI: 10.1002/art.28335

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