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Published on: December 7, 2014
Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind,
Janet Pope1, Donna McBain, Lisa Petrlich
1St. Joseph's Health Care and University of Western Ontario, London, Ontario, Canada. janet.pope@sjhc.london.on.ca
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.
Insights
Imatinib treatment for diffuse cutaneous systemic sclerosis (dcSSc) showed poor tolerability and high adverse event rates, leading to study discontinuation. The small sample size prevented efficacy conclusions for this tyrosine kinase inhibitor in SSc patients.
Area of Science:
- Rheumatology
- Dermatology
- Pharmacology
Background:
- Diffuse cutaneous systemic sclerosis (dcSSc) is a severe autoimmune condition characterized by ত্বক thickening and organ involvement.
- Current treatments for dcSSc have limited efficacy and significant side effects.
- Targeting specific molecular pathways, such as tyrosine kinases, offers a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the feasibility and safety of imatinib, a tyrosine kinase inhibitor, in patients with active diffuse cutaneous systemic sclerosis (dcSSc).
- To assess the preliminary efficacy of imatinib by monitoring skin thickness, patient-reported outcomes, and biomarkers.
Main Methods:
- A 6-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study.
- 10 patients with active dcSSc were enrolled, with a 4:1 randomization to imatinib (200 mg twice daily) or placebo.
- Data collected included safety, modified Rodnan skin thickness scores (MRSS), Health Assessment Questionnaire (HAQ) scores, global assessments, and biomarkers.
Main Results:
- The study was discontinued early due to poor tolerability and high rates of adverse events in patients receiving imatinib.
- No significant difference in MRSS or other efficacy measures was observed between imatinib and placebo groups.
- Common side effects included edema, fatigue, nausea, and anemia, with two hospitalizations due to adverse events.
Conclusions:
- Imatinib demonstrated poor tolerability in patients with active dcSSc, potentially limiting its therapeutic application.
- The study's small size and early termination precluded definitive conclusions regarding imatinib's efficacy in treating dcSSc.
