title: A randomized, blinded, parallel group, placebo controlled pilot study evaluating the effect of PVAC treatment in patients with diffuse systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a disorder characterized by progressive thickening of the skin; there is no effective therapy. PVAC, a potential therapeutic agent derived from delipidated, deglycolipidated Mycobacterium vaccae, has shown effects on cutaneous disease in animal models of SSc. We evaluated the safety and possible biologic effect of intradermal injections of PVAC in patients with diffuse SSc.
  
  
  METHODS
  Eighteen patients enrolled in this double blind, placebo controlled, randomized, 24 week pilot study. All patients met criteria for diffuse SSc without evidence of significant renal dysfunction, pulmonary fibrosis, pulmonary hypertension, or congestive heart failure. Patients received 8 intradermal injections of 15 microg PVAC, 50 microg PVAC, or placebo at 3 week intervals. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at Week 24. Each of the active drug arms was compared to placebo.
  
  
  RESULTS
  Baseline demographic and disease characteristics were similar across the 3 treatment groups. The median age was 48 years and 14 of 18 (78%) patients were female. The regimens were well tolerated with no reported serious adverse events; however, grade 1 or 2 injection site reactions occurred in the majority of patients receiving PVAC. The MRSS improved by 20.6% in the 15 microg PVAC arm, while it worsened by 29.8% in the placebo arm and by 16.7% in the 50 microg arm. Change in physician and patient global assessments followed similar trends.
  
  
  CONCLUSIONS
  In this pilot study, use of PVAC in patients with SSc appeared safe and was associated with a trend toward improved skin scores in the 15 microg treatment group. Additional evaluation of this therapeutic approach is warranted.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA. genovese@stanford.edu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: Eliza F
authors.initials: EF
authors.lastname: Chakravarty
authors.forename: David L
authors.initials: DL
authors.lastname: Boyle
authors.forename: Zuhre
authors.initials: Z
authors.lastname: Tutuncu
authors.forename: Christine M
authors.initials: CM
authors.lastname: Thorburn
authors.forename: Merita
authors.initials: M
authors.lastname: Halilhodzic
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: Jan
authors.initials: J
authors.lastname: Baughman
authors.forename: Stanford
authors.initials: S
authors.lastname: Stewart
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
mesh_terms: D000328:Adult; D000368:Aged; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D010865:Pilot Projects; D012595:Scleroderma, Systemic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018180:Thrombomodulin / Q000097:blood; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001428:Bacterial Vaccines; D015415:Biomarkers; D019040:E-Selectin; D018180:Thrombomodulin; D015164:Vaccines, Inactivated