Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes

Edwards, Jonathan; Cambridge, G

doi:10.1093/rheumatology/40.2.205

Cited by 470 publications

(294 citation statements)

References 25 publications

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“…The detailed clinical responses in these patients have been reported previously (9,15). The majority of patients showed substantial clinical improvement, which was sustained for up to 33 months and up to 17 months after the return of circulating B lymphocytes.…”

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confidence: 58%

“…Patients were treated in 5 cohorts with a range of doses of rituximab, with or without intravenous cyclophosphamide and/or oral prednisolone, over a 2-4-week period (9,15). Disease-modifying antirheumatic drugs (excluding steroids) were discontinued from day 0.…”

Section: Methodsmentioning

confidence: 99%

“…B lymphocyte depletion has recently been introduced as a therapy for a range of autoantibody-associated disorders, including RA, IgM-associated neuropathies, immune thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, and dermatomyositis (9)(10)(11)(12)(13)(14)(15). Encouraging results have been reported, and a randomized controlled trial of this therapy in RA is currently in progress.…”

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confidence: 99%

“…However, B lymphocyte depletion with rituximab alone is probably incomplete, and in patients with lymphoma, long-term benefit from rituximab is increased by combination with other drugs (20). For these reasons, in the treatment of RA, it has initially been used in combination with cyclophosphamide and corticosteroid (9).…”

mentioning

confidence: 99%

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Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Cambridge¹,

Leandro²,

Edwards³

et al. 2003

Arthritis & Rheumatism

413

259

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Objective. To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA).Methods. B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed.Results. The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change.Conclusion. Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.

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confidence: 58%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Cambridge¹,

Leandro²,

Edwards³

et al. 2003

Arthritis & Rheumatism

413

259

View full text Add to dashboard Cite

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“…The efficacy of anti-CD20 therapy in RA (8,9) confirms that B cells play a pathogenic role and presents new treatment possibilities. The presence of antibodies to CD20 leads to depletion of B cells but not of long-lived plasma cells, and it takes time for the antibody levels to decrease.…”

Section: Conclusion Ides Has Therapeutic Potential In Igg Antibody-mmentioning

confidence: 81%

Blocking of experimental arthritis by cleavage of IgG antibodies in vivo

Nandakumar¹,

Johansson²,

Björck³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis.Methods. Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibodyinduced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed. Results. IdeS efficiently cleaved mouse

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Rituximab for rheumatoid arthritis

Palylyk-Colwell¹,

McGahan²

2008

Cochrane Database of Systematic Reviews

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Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes

Abstract: These findings are consistent with the concept that RA is critically dependent on B lymphocytes and suggest that B-lymphocyte depletion may be a safe and effective therapy.

Cited by 470 publications

References 25 publications

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Blocking of experimental arthritis by cleavage of IgG antibodies in vivo

Rituximab for rheumatoid arthritis

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