EXTENDED REPORT

Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion

M J Leandro, J C W Edwards, G Cambridge

Centre for Rheumatology, University College London, UK

Correspondence to:
Correspondence to:
Professor J C W Edwards, Centre for Rheumatology, Arthur Stanley House, 40–50 Tottenham Street, London W1T 4NJ, UK;
jo.edwards{at}ucl.ac.uk

Objectives: To obtain evidence for dose response and to extend evidence of safety and efficacy for B lymphocyte depletion in rheumatoid arthritis.

Methods: Twenty two patients with rheumatoid arthritis received a total of 29 treatments with five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or high dose prednisolone (PR) on an open basis as follows; cohort I: RTX 1400 mg/m², CP 750x2+PR; cohort II: RTX 300–700 mg/m², -CP±PR); cohort III: RTX 600–700 mg/m², CP 750x2+PR; cohort IV: RTX 1200 mg/m², CP 750x2-PR; cohort V: RTX 500 mg/m², CP 750x2+PR. American College of Rheumatology (ACR) criteria of improvement at six months were chosen as the primary outcome measure. Disease activity scores and total duration of improvement and of B cytopenia were also recorded.

Results: No major adverse events attributable to treatment were seen. ACR grades of improvement at six months were as follows: cohort I: ACR70x3, ACR50x2; cohort II: ACR20x1, ACR0x3; cohort III: ACR70x6, ACR50x2, ACR20x2; cohort IV: ACR70x2, ACR50x2, ACR20x1, ACR0x1; cohort V: ACR0x4.

Conclusions: B lymphocyte depletion in rheumatoid arthritis has so far proved to be safe and associated with major improvement with protocols including RTX 600 mg/m² or more and CP, but not with more limited protocols. These observations provide an initial basis for the design of formal trials of B cell depletion and other B cell directed treatments, including a phase II controlled trial now in progress.

Keywords: rituximab; anti-CD20; rheumatoid arthritis; autoimmunity

Abbreviations: ACR, American College of Rheumatology; DMARDs, disease modifying antirheumatic drugs; RA, rheumatoid arthritis; RF, rheumatoid factor; TNF, tumour necrosis factor

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