OBJECTIVE: To determine the safety of rituximab, to provide preliminary data regarding the potential efficacy of rituximab, and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Fifteen patients with dcSSc, all of whom experienced their first non-Raynaud's disease-associated disease manifestation within 18 months of trial entry, were recruited to receive 2 intravenous doses of rituximab (1,000 mg), administered 2 weeks apart. Safety, clinical, and exploratory outcomes were evaluated at baseline and at 6 months. The primary outcome was the change in the modified Rodnan skin thickness score (MRSS) at 6 months compared with baseline. RESULTS: Adverse events included frequent infusion reactions and rare infections (urinary tract infection and dental abscess occurred in 1 patient each). The mean change in the MRSS between baseline and 6 months was not significant. Results of pulmonary function tests and other measures of major organ involvement were stable. The modest B cell infiltrates that were present in most skin biopsy specimens at baseline were completely depleted at 6 months in most patients. Autoantibody titers showed only modest and variable changes after treatment. CONCLUSION: In this pilot study, treatment with rituximab appeared to be safe and well tolerated among patients with dcSSc. Rituximab treatment resulted in both depletion of circulating B cells and depletion of dermal B cells but had little effect on the levels of SSc-associated autoantibodies. Rituximab treatment did not appear to result in a significant beneficial effect on skin disease. The potential efficacy of rituximab in other organs such as the lung could not be clearly evaluated in this small open-label trial.
OBJECTIVE: To determine the safety of rituximab, to provide preliminary data regarding the potential efficacy of rituximab, and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Fifteen patients with dcSSc, all of whom experienced their first non-Raynaud's disease-associated disease manifestation within 18 months of trial entry, were recruited to receive 2 intravenous doses of rituximab (1,000 mg), administered 2 weeks apart. Safety, clinical, and exploratory outcomes were evaluated at baseline and at 6 months. The primary outcome was the change in the modified Rodnan skin thickness score (MRSS) at 6 months compared with baseline. RESULTS: Adverse events included frequent infusion reactions and rare infections (urinary tract infection and dental abscess occurred in 1 patient each). The mean change in the MRSS between baseline and 6 months was not significant. Results of pulmonary function tests and other measures of major organ involvement were stable. The modest B cell infiltrates that were present in most skin biopsy specimens at baseline were completely depleted at 6 months in most patients. Autoantibody titers showed only modest and variable changes after treatment. CONCLUSION: In this pilot study, treatment with rituximab appeared to be safe and well tolerated among patients with dcSSc. Rituximab treatment resulted in both depletion of circulating B cells and depletion of dermal B cells but had little effect on the levels of SSc-associated autoantibodies. Rituximab treatment did not appear to result in a significant beneficial effect on skin disease. The potential efficacy of rituximab in other organs such as the lung could not be clearly evaluated in this small open-label trial.
Authors: J R Seibold; J H Korn; R Simms; P J Clements; L W Moreland; M D Mayes; D E Furst; N Rothfield; V Steen; M Weisman; D Collier; F M Wigley; P A Merkel; M E Csuka; V Hsu; S Rocco; M Erikson; J Hannigan; W S Harkonen; M E Sanders Journal: Ann Intern Med Date: 2000-06-06 Impact factor: 25.391
Authors: Donald P Tashkin; Robert Elashoff; Philip J Clements; Jonathan Goldin; Michael D Roth; Daniel E Furst; Edgar Arriola; Richard Silver; Charlie Strange; Marcy Bolster; James R Seibold; David J Riley; Vivien M Hsu; John Varga; Dean E Schraufnagel; Arthur Theodore; Robert Simms; Robert Wise; Fredrick Wigley; Barbara White; Virginia Steen; Charles Read; Maureen Mayes; Ed Parsley; Kamal Mubarak; M Kari Connolly; Jeffrey Golden; Mitchell Olman; Barri Fessler; Naomi Rothfield; Mark Metersky Journal: N Engl J Med Date: 2006-06-22 Impact factor: 91.245
Authors: Eugene Y Kissin; Aileen M Schiller; Rondi B Gelbard; Jennifer J Anderson; Vincent Falanga; Robert W Simms; Joseph H Korn; Peter A Merkel Journal: Arthritis Rheum Date: 2006-08-15
Authors: Christopher P Denton; Peter A Merkel; Daniel E Furst; Dinesh Khanna; Paul Emery; Vivien M Hsu; Nancy Silliman; James Streisand; John Powell; Anita Akesson; John Coppock; Frank van den Hoogen; Ariane Herrick; Maureen D Mayes; Douglas Veale; Joanna Haas; Stephen Ledbetter; Joseph H Korn; Carol M Black; James R Seibold Journal: Arthritis Rheum Date: 2007-01
Authors: P J Clements; D E Furst; W K Wong; M Mayes; B White; F Wigley; M H Weisman; W Barr; L W Moreland; T A Medsger; V Steen; R W Martin; D Collier; A Weinstein; E Lally; J Varga; S Weiner; B Andrews; M Abeles; J R Seibold Journal: Arthritis Rheum Date: 1999-06
Authors: Michael L Whitfield; Deborah R Finlay; John Isaac Murray; Olga G Troyanskaya; Jen-Tsan Chi; Alexander Pergamenschikov; Timothy H McCalmont; Patrick O Brown; David Botstein; M Kari Connolly Journal: Proc Natl Acad Sci U S A Date: 2003-10-06 Impact factor: 11.205
Authors: Dimitrios Daoussis; Stamatis-Nick C Liossis; Athanassios C Tsamandas; Christina Kalogeropoulou; Alexandra Kazantzi; Chaido Sirinian; Maria Karampetsou; Georgios Yiannopoulos; Andrew P Andonopoulos Journal: Rheumatology (Oxford) Date: 2009-05-15 Impact factor: 7.580