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Tasigna showed tolerability, mRSS improvement in pilot study of patients with SSc
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In a pilot study of patients with diffuse cutaneous systemic sclerosis who were treated with Tasigna, the majority tolerated the treatment and some showed improvements in modified Rodnan Skin Scores, according to the results from the open-label, pilot study.
Ten patients with early systemic sclerosis (SSc) who met the 1980 American College of Rheumatology were recruited between November 2010 and December 2011 into an investigator-initiated, open-label, single-center pilot study. Patients were a mean age of 46 years, 80% women, presented with diffuse cutaneous SSc (dcSSc) and had a median disease duration of 0.7 years. Nine patients were anti-nuclear antibody-positive while three were anti-Scl-positive and five were RNA polymerase III-positive. The mean modified Rodnan Skin Score (mRSS) was 30.1 at baseline and greater than 16 in all patients.
Patients were excluded in the presence of a baseline corrected QT (QTc) interval on EKG of 450 msec or above, treatment with immunosuppressants within 3 months prior to enrollment, pregnancy, another serious medical condition, diffusion capacity of carbon monoxide (DLCO) up to 30% predicted or ejection fraction (EF) up to 50%.
Patients received 200mg Tasigna (nilotinib, Novartis), a tyrosine kinase inhibitor, daily for 1 week which was titrated to 200mg twice daily for 3 weeks before increasing the dose to 400mg twice daily. A 12-lead EKG was used to measure the QTc interval of each patient 1 week after each change in dosage.
Punch biopsies of forearm skin were collected and analyzed at baseline and biopsies after treatment were collected at 1 cm distance from the previous biopsy site.
During the 12-month treatment cycle, 71 adverse events were observed, 75% of which were considered to have a possible relationship with treatment with nilotinib. Most (92%) were grade 1 or grade 2 and included grade 1, asymptomatic, abnormal liver function tests observed in 50% of patients. In 60% of patients, grade 1 or 2 QTc prolongation was observed, resulting in the discontinuation of two patients. Four patients had normalized QTc following additional EKG monitoring or dosage reduction.
The mRSS improved by 23% from a mean of 26.9 to 20.6 in the seven patients who completed 12 months of treatment. No statistical difference from baseline was seen in mean skin thickness at 6 or 12 months. – by Shirley Pulawski
Disclosure: Gordon reports support from a New Investigator Grant from the Scleroderma Foundation and by the Clinician Scientist Development Award through the Kellen Foundation at the Hospital for Special Surgery. Please see the full study for a list of all other authors’ relevant financial disclosures.
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