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Extended report
An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis
  1. C P Denton1,
  2. M Engelhart2,
  3. N Tvede2,
  4. H Wilson1,
  5. K Khan1,
  6. X Shiwen1,
  7. P E Carreira3,
  8. F Diaz Gonzalez4,
  9. C M Black1,
  10. F H van den Hoogen5
  1. 1
    Royal Free Hospital, London, UK
  2. 2
    Herlev University Hospital and Rigshospitalet, Copenhagen, Denmark
  3. 3
    Hospital 12 de Octubre, Madrid, Spain
  4. 4
    University Hospital, Tenerife, Canary Islands
  5. 5
    University Hospital, Nijmegen, The Netherlands
  1. Correspondence to Professor C P Denton, Centre for Rheumatology, Royal Free Hospital, Pond Street, London NW3 2QG, UK; c.denton{at}medsch.ucl.ac.uk

Abstract

Aim: 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).

Conclusion: 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.

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Footnotes

  • Funding This trial was sponsored by Royal Free and University College Medical School. Research in the department is supported by the Arthritis Research Campaign, Raynaud’s and Scleroderma Association and the Scleroderma Society (UK). The authors also obtain support from the Scleroderma Research Foundation (USA).

  • Competing interests Declared. This investigator-initiated study was supported by a research grant from Centocor, Inc, who also provided the study medication.

  • Ethics approval The protocol and patient informed consent forms were approved by the responsible ethics committees at participating sites.

  • Patient consent Obtained.

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