PMID- 21769849
OWN - NLM
STAT- MEDLINE
DCOM- 20130125
LR  - 20220309
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 63
IP  - 11
DP  - 2011 Nov
TI  - A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the 
      treatment of systemic sclerosis-associated active interstitial lung disease.
PG  - 3540-6
LID - 10.1002/art.30548 [doi]
AB  - OBJECTIVE: Transforming growth factor beta (TGFbeta) and platelet-derived growth factor 
      (PDGF) may play a critical role in systemic sclerosis (SSc)-related interstitial 
      lung disease (ILD), and imatinib is a potent inhibitor of TGFbeta and PDGF 
      production. In this 1-year, phase I/IIa open-label pilot study of imatinib in 
      patients with SSc-related active ILD, our primary aim was to assess the safety of 
      imatinib; we also explored its efficacy. METHODS: We recruited 20 SSc patients 
      with a forced vital capacity (FVC) of <85% predicted, dyspnea on exertion, and 
      presence of a ground-glass appearance on high-resolution computed tomography. 
      Patients received oral therapy with imatinib (up to 600 mg/day) for a period of 1 
      year. Adverse events were recorded, pulmonary function was tested, and the 
      modified Rodnan skin thickness score (MRSS) was assessed every 3 months. The 
      course of changes in lung function, the Health Assessment Questionnaire (HAQ) 
      disability index (DI), and the MRSS were modeled over the period of study to 
      explore treatment efficacy. RESULTS: The majority of patients were female (65%), 
      Caucasian (75%), and had diffuse cutaneous SSc (70%). At baseline, the mean +/- SD 
      FVC % predicted was 65.2 +/- 14.0 and the mean +/- SD MRSS was 18.7 +/- 10.1. The mean 
      +/- SD dosage of imatinib was 445 +/- 125 mg/day. Of the 20 SSc patients, 12 
      completed the study, 7 discontinued because of adverse events (AEs), and 1 
      patient was lost to followup. Common AEs (>/=20%) included fatigue, facial/lower 
      extremity edema, nausea and vomiting, diarrhea, generalized rash, and new-onset 
      proteinuria. Treatment with imatinib showed a trend toward improvement in the FVC 
      % predicted (1.74%; P not significant) and the MRSS (3.9 units; P < 0.001). 
      CONCLUSION: Use of high-dose daily therapy with imatinib (600 mg/day) in SSc 
      patients with ILD was associated with a large number of AEs. Our experience with 
      AEs suggests that dosages of imatinib lower than 600 mg/day may be appropriate 
      and that further dose ranging analysis is needed in order to understand the 
      therapeutic index of imatinib in SSc.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Khanna, Dinesh
AU  - Khanna D
AD  - David Geffen School of Medicine, University of California, Los Angeles, USA. 
      khannad@med.umich.edu
FAU - Saggar, Rajeev
AU  - Saggar R
FAU - Mayes, Maureen D
AU  - Mayes MD
FAU - Abtin, Fereidoun
AU  - Abtin F
FAU - Clements, Philip J
AU  - Clements PJ
FAU - Maranian, Paul
AU  - Maranian P
FAU - Assassi, Shervin
AU  - Assassi S
FAU - Saggar, Rajan
AU  - Saggar R
FAU - Singh, Ram R
AU  - Singh RR
FAU - Furst, Daniel E
AU  - Furst DE
LA  - eng
SI  - ClinicalTrials.gov/NCT00512902
GR  - K23 AR053858/AR/NIAMS NIH HHS/United States
GR  - K23 AR053858-04/AR/NIAMS NIH HHS/United States
GR  - R01 AI080778/AI/NIAID NIH HHS/United States
GR  - K23-AR-053858-04/AR/NIAMS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
CIN - Arthritis Rheum. 2011 Nov;63(11):3199-203. PMID: 21769846
MH  - Adult
MH  - Benzamides
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate
MH  - Lung Diseases, Interstitial/*drug therapy/etiology
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Piperazines/adverse effects/*therapeutic use
MH  - Prospective Studies
MH  - Protein Kinase Inhibitors/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Scleroderma, Systemic/*complications
MH  - Treatment Outcome
PMC - PMC3205223
MID - NIHMS310356
EDAT- 2011/07/20 06:00
MHDA- 2013/01/26 06:00
PMCR- 2012/11/01
CRDT- 2011/07/20 06:00
PHST- 2011/07/20 06:00 [entrez]
PHST- 2011/07/20 06:00 [pubmed]
PHST- 2013/01/26 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - 10.1002/art.30548 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2011 Nov;63(11):3540-6. doi: 10.1002/art.30548.