Nilotinib Tasigna™ in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trialReportar como inadecuado

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Arthritis Research and Therapy

, 17:213

First Online: 18 August 2015Received: 13 January 2015Accepted: 20 July 2015


IntroductionTyrosine kinase inhibitors TKI are medications of interest in the treatment of Systemic Sclerosis SSc because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous dcSSc with the TKI nilotinib Tasigna™.

MethodsTen adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score MRSS after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray.

ResultsPatients had early and active dcSSc with median disease duration of 0.7 years range 0.5, 1.7 and increasing MRSS in the month prior to baseline mean +2.9, p=0.02. Seven out of ten patients completed 6 and 12 months of treatment. Seventy-one adverse events AEs including 2 serious AEs were observed, and 92 % of AEs were grade 1-2. Two patients discontinued the medication due to mild QTc prolongation. MRSS improved by a mean of 4.2 points 16 % at 6 months and by 6.3 points 23 % at 12 months in the 7 completers, p=0.02 and 0.01, respectively. Patients with a decrease in MRSS >20 % from baseline at 12 months classified as improvers had significantly higher expression of transforming growth factor beta receptor TGFBR and platelet-derived growth factor receptor beta PDGFRB signaling genes at baseline than non-improvers, and the expression of these genes significantly decreased in improvers post-treatment.

ConclusionNilotinib was well tolerated by the majority of patients in this study, with tolerability limited primarily by mild QTc-prolongation. Significant MRSS improvement was observed in these early, active patients, but is not conclusive of treatment effect given the open-label study-design and small number of patients in this pilot study. Improvers had higher levels of expression of genes associated with TGFBR and PDGFRB signaling at baseline, and a significant decrease in the expression of these genes occurred only in patients with higher MRSS improvement. The findings of this pilot study warrant more conclusive evaluation.

Trial NCT01166139, July 1, 2010.

AbbreviationsABI1abl-interactor 1

ACTBactin beta

AEadverse event

cAblAbelson murine leukemia viral oncogene homolog

CADcoronary artery disease

CCL2chemokine C-C motif ligand 2

CMLchronic myelogenous leukemia

COL15A1collagen 15a1

dcSScdiffuse cutaneous systemic sclerosis

DLCOdiffusion lung capacity of carbon monoxide

EFejection fraction

EGRearly growth response protein


ESRerythrocyte sedimentation rate

FDRfalse discovery rate

FVCforced vital capacity

GSEAgene set enrichment analysis

HandEhematoxylin and eosin

ICAM1intercellular adhesion molecule 1

IL23Ainterleukin 23A

ILDinterstitial lung disease

lcSSclimited cutaneous systemic sclerosis

MMP14matrix metalloproteinase 14

MRSSmodified Rodnan skin score

NFKBnuclear factor kappa-light-chain-enhancer of activated B cells


PDGFplatelet-derived growth factor

PDGFRplatelet-derived growth factor receptor

PFTpulmonary function test

PGAphysician global assessment


QTccorrected QT interval - referring to an interval on an electrocardiogram

SAEserious adverse event

SF-36short form 36-item health survey

SF-36 MCshort form 36-item health survey mental component

SF-36 PCshort form 36-item health survey physical component

SHAQ-DIscleroderma health assessment questionnaire - disability index

SIGLEC7sialic acid-binding immunoglobulin-type lectin 7

SScsystemic sclerosis


TGFBtransforming growth factor beta

TGFBRtransforming growth factor beta receptor

TKItyrosine kinase inhibitor

αSMAalpha smooth muscle actin

Electronic supplementary materialThe online version of this article doi:10.1186-s13075-015-0721-3 contains supplementary material, which is available to authorized users.

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Autor: Jessica K. Gordon - Viktor Martyanov - Cynthia Magro - Horatio F. Wildman - Tammara A. Wood - Wei-Ti Huang - Mary K. Cr


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