An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

Christopher P Denton ^1*, Merete Engelhart ², Niels Tvede ², Helen Wilson ¹, Korsa Khan ¹, Xu Shiwen ¹, Patricia E Carreira ³, Frederic Diaz Gonzalez ⁴, Carol M Black ¹ and Frank H van den Hoogen ⁵

¹ Centre for Rheumatology, Royal Free Hospital, United Kingdom
² Herlev University Hospital, Copenhagen, Denmark
³ Hospital 12 de Octubre, Madrid, Spain
⁴ University Hospital, Tenerife, Spain
⁵ University Hospital, Nijmegen, Netherlands

^* To whom correspondence should be addressed. E-mail: c.denton{at}medsch.ucl.ac.uk.

Accepted 22 August 2008

Abstract

Aim: We have examined the safety and potential efficacy of a chimaeric anti-TNFÑ monoclonal antibody (infliximab) in diffuse cutaneous SSc.

Methods: This was a 26 week open-label pilot study in which 16 cases of dcSSc received 5 infusions of infliximab (5mg/kg). Clinical assessment included skin sclerosis score, scleroderma-HAQ, self-reported functional score and physician global VAS. Collagen turnover, skin biopsy analysis and full safety evaluation was performed.

Results: There was no significant change in skin score at 26 weeks but a trend for lower MRSS at 22 weeks (17, 6-46) compared with peak value (29, 11-44; p=0.10). Serum amino-terminal propeptide of type III collagen (PIIINP) level was significantly lower at week 26 compared with baseline (p=0.03). Secretion of type I collagen by dermal fibroblast 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 (SUSARs). There were 21 serious adverse events (SAE) that occurred in 7 subjects, mostly attributable to dcSSc. There were 127 distinct adverse events (AE), occurring in 16 subjects. Of these 19 AE (15%) were probably or definitely related to infliximab treatment. 8 (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in 5 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 fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in SSc.