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Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study

Paolo Fraticelli1, Barbara Gabrielli1, Giovanni Pomponio1, Gabriele Valentini2, Silvia Bosello3, Piersandro Riboldi4, Maria Gerosa5, Paola Faggioli6, Roberto Giacomelli7, Nicoletta Del Papa8, Roberto Gerli9, Claudio Lunardi10, Stefano Bombardieri11, Walter Malorni12, Angelo Corvetta13, Gianluca Moroncini114, Armando Gabrielli114* and on behalf of Imatinib in Scleroderma Italian Study Group

Author Affiliations

1 Clinica Medica, Department of Internal Medicine, Ospedali Riuniti Ancona, Via Conca 71, 60020 Ancona, Italy

2 Rheumatology unit, Second University of Naples, Via Pansini, 5 80131 Naples, Italy

3 Division of Rheumatology, Catholic University, Via G. Moscati, 31 - Rome, 00168, Italy

4 Allergy, Clinical Immunology & Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Department of Internal Medicine, University of Milan, Piazzale Brescia, 20, 20149 Milan, Italy

5 Department of Clinical Sciences and Community Health, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy

6 Internal Medicine, Ospedale Nuovo di Legnano, Via Papa Giovanni Paolo II, 20010 Legnano, Italy

7 Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, University of L'Aquila, Piazzale Salvatore Tommasi 1, 67100 Coppito, L'Aquila, Italy

8 Rheumatology Unit, Ospedale “G. Pini”, Piazza Cardinale Andrea Ferrari, 1, 20122 Milan, Italy

9 Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo - padiglione X, 06122 Perugia, Italy

10 Clinical Immunology and Rheumatology, Department of Medicine, University of Verona, P. le L.A. Scuro 10, 37134 Verona, Italy

11 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy

12 Department of Drug Therapy and Medicine Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy

13 Internal Medicine and Rheumatology, Ospedale degli Infermi, Viale Luigi Settembrini, 2, 47923 Rimini, Italy

14 Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Via Tronto 10/A, 60100 Ancona, Italy

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Arthritis Research & Therapy 2014, 16:R144  doi:10.1186/ar4606

Published: 8 July 2014



Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.


Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A “good response” was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DLCO) >15% and PaO2 > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.


Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.


Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics.

Trial registration NCT00573326. Registered 13 December 2007.