Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month,
randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a
single center.
Author(s): Pope J, McBain D, Petrlich L, Watson S, Vanderhoek L, de Leon F, Seney S, Summers
K.
Affiliation(s): St. Joseph's Health Care and University of Western Ontario, London, Ontario,
Canada. janet.pope@sjhc.london.on.ca
Publication date & source: 2011, Arthritis Rheum. , 63(11):3547-51
OBJECTIVE: To better understand the feasibility of using imatinib, a tyrosine
kinase inhibitor, to treat active diffuse cutaneous systemic sclerosis (dcSSc).
METHODS: We performed a 6-month, randomized, double-blind, placebo-controlled,
proof-of-concept pilot study of imatinib in patients with active dcSSc. Data on
safety, modified Rodnan skin thickness scores (MRSS), Health Assessment
Questionnaire (HAQ) scores, patient's and physician's global assessments (100-mm
visual analog scale), and biomarkers in serum and skin biopsy samples were
collected. We used a 4:1 randomization strategy (imatinib 200 mg administered
twice a day versus placebo), stratifying according to current use of
methotrexate. The plan was to enroll 20 dcSSc patients.
RESULTS: After enrolling 10 patients (9 receiving active drug and 1 receiving
placebo), we found poor tolerability and high rates of adverse events with
imatinib, and study enrollment was discontinued. There was no significant
difference in the mean MRSS in all patients who took imatinib (31.1 at baseline
versus 29.4 at 6 months) or in only those who completed 6 months of imatinib
(31.0 at baseline versus 30.3 at 6 months), and there was no difference in the
C-reactive protein level, erythrocyte sedimentation rate, physician's global
assessment, patient's global assessment, response to the Health Transition query,
or the HAQ scores between those who did and those who did not complete 6 months
of therapy. Side effects were edema, fluid retention, fatigue, nausea,
cramps/myalgias, diarrhea, alopecia, and anemia. Most side effects occurred
within the first week of treatment, and even when imatinib was reintroduced at a
lower dosage (200 mg daily), it was poorly tolerated. Two patients were
hospitalized because of side effects of the medication. In general, biomarker
levels in plasma and skin did not change.
CONCLUSION: Imatinib was poorly tolerated, and this could limit its application
in SSc. The study was too small to form conclusions about the efficacy of
imatinib in SSc.
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