title: Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial.
abstract: OBJECTIVE
  To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc).
  
  
  METHODS
  In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment.
  
  
  RESULTS
  Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=-4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology.
  
  
  CONCLUSIONS
  Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581.
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. spierar@hss.edu
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spiera
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Gordon
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Mersten
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
authors.forename: Mansi
authors.initials: M
authors.lastname: Mehta
authors.forename: Horatio F
authors.initials: HF
authors.lastname: Wildman
authors.forename: Stacey
authors.initials: S
authors.lastname: Kloiber
authors.forename: Kyriakos A
authors.initials: KA
authors.lastname: Kirou
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyman
authors.forename: Mary K
authors.initials: MK
authors.lastname: Crow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D001706:Biopsy; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000503:physiopathology; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D045743:Scleroderma, Diffuse / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D016896:Treatment Outcome; D014463:Ultrasonography; D014797:Vital Capacity / Q000187:drug effects; D055815:Young Adult
chemical_list: D001549:Benzamides; D003879:Dermatologic Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate