title: An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis.
abstract: OBJECTIVE
  The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc).
  
  
  METHODS
  A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg/kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed.
  
  
  RESULTS
  There was no significant change in skin score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0.025).
  
  
  CONCLUSIONS
  In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis.
authors.affiliation: Centre for Rheumatology, Royal Free Hospital, Pond Street, London NW3 2QG, UK. c.denton@medsch.ucl.ac.uk
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
authors.forename: M
authors.initials: M
authors.lastname: Engelhart
authors.forename: N
authors.initials: N
authors.lastname: Tvede
authors.forename: H
authors.initials: H
authors.lastname: Wilson
authors.forename: K
authors.initials: K
authors.lastname: Khan
authors.forename: X
authors.initials: X
authors.lastname: Shiwen
authors.forename: P E
authors.initials: PE
authors.lastname: Carreira
authors.forename: F
authors.initials: F
authors.lastname: Diaz Gonzalez
authors.forename: C M
authors.initials: CM
authors.lastname: Black
authors.forename: F H
authors.initials: FH
authors.lastname: van den Hoogen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D045743:Scleroderma, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D024042:Collagen Type I; D003879:Dermatologic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab