Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

Silverman, Gregg J.; Weisman, Stuart

doi:10.1002/art.10947

Cited by 343 publications

(212 citation statements)

References 51 publications

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…Initial data have shown rituximab to be efficacious and relatively safe in the treatment of systemic diseases such as RA, Wegener's granulomatosis, and SLE (7,9,23). Although SS is considered to be a T cell-mediated disease, its systemic complications are associated with increased B cell activity.…”

Section: Discussionmentioning

confidence: 99%

“…The MFI is a 20-item self-report scale, which has been validated for SS (20) and is designed to objectively measure fatigue, including the following dimensions: 1) general fatigue, 2) physical fatigue, 3) mental fatigue, 4) reduced motivation, and 5) reduced activity. A higher score (possible range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] indicates a higher level of fatigue. The SF-36 questionnaire, which has been used for measuring subjective well-being, has also been validated for SS (21).…”

Section: Methodsmentioning

confidence: 99%

“…Rituximab, a chimeric murine/human anti-CD20 monoclonal antibody that binds to the B cell surface antigen CD20, is currently used in the treatment of B cell lymphomas (4)(5)(6). It is also considered a promising agent for treatment of various autoimmune disorders, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (7)(8)(9). It has been hypothesized that because B cells appear to be involved in the pathogenesis of SS, B cell depletion may lead to a decrease of disease activity.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study

Pijpe

Imhoff²,

Spijkervet

et al. 2005

Arthritis & Rheumatism

447

300

View full text Add to dashboard Cite

Objective. To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosaassociated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS).Methods. Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/ primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m 2 ) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/ lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.Results. Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human antichimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.Conclusion. Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study

Pijpe

Imhoff²,

Spijkervet

et al. 2005

Arthritis & Rheumatism

447

300

View full text Add to dashboard Cite

show abstract

“…It induces 98% depletion of peripheral blood B cells, but only 40-70% of lymph node B cells are depleted [3]. The death of B cells appears as a result from the induction of complement-mediated events, through antibody-mediated apoptosis and antibodydependent cellular cytotoxicity [8].…”

Section: Introductionmentioning

confidence: 99%

Off‐Trial Evaluation of the B cell–Targeting Treatment in the Refractory Cases of Antineutrophil Cytoplasmic Antibodies (ANCA)‐Associated Vasculitis: Long‐Term Follow‐Up from a Single Centre

et al. 2012

View full text Add to dashboard Cite

The aim of the study was to evaluate long‐term clinical and immunological effects of anti‐B cell treatment in patients with antineutrophil cytoplasmic antibodies (ANCA)‐associated vasculitis refractory to conventional immunosuppressive treatment. Rituximab (RTX) was added to the ongoing immunosuppressive treatment in 29 patients with refractory ANCA‐associated vasculitis. The disease activity was measured using Birmingham Vasculitis Activity Score/Wegener’s granulomatosis (BVAS/WG score), and clinical laboratory variables were recorded. The median BVAS/WG score before treatment was 6 (IQR 3–8), and 28 patients (97%) had disease flare classified either severe (62%) or limited (34%). Six of 29 patients (21%) achieved a complete remission, and 12 (41%) had a treatment response with ≥50% decrease in BVAS/WG score at 6 months. Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow‐up period. Three patients had renal flare and were successfully re‐treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea‐subglottic granulomatous disease. RTX is a potent therapeutic option for ANCA‐associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations.

show abstract

“…Furthermore, the discordance between the ability of rituximab to mediate rapid B cell depletion in vivo (7,8) (hours to days) and the delay in maximal treatment effect (weeks to months) implies that downstream effects of B cell loss likely contribute to clinical improvement (9). Based on these observations, recent studies have tested the hypothesis that the use of rituximab in combination with other immunomodulatory agents may provide additive or synergistic therapeutic benefit (10).…”

mentioning

confidence: 99%

Anti-CD20 Antibody with Multimerized Fc Domains: A Novel Strategy To Deplete B Cells and Augment Treatment of Autoimmune Disease

Zhang

Olsen

Chen

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

We developed a fully recombinant anti-CD20 protein derived from cDNA encoding one Fab domain, two IgG1 Fc regions, the IgG2 hinge, and an isoleucine zipper. This protein, called GB4542, contained both the homodimer and higher-order multimers. Binding studies revealed that GB4542 preferentially bound CD20+ cells yet also recognized CD20−FcγR+ PBMC. In contrast, a control mAb containing the identical Fab region, GB4500, failed to bind CD20−FcγR+ PBMC. Consistent with these findings, interactions between GB4542 and the canonical FcγRs had substantially lower KD values than correlate interfaces between GB4500 and these receptors. At low concentrations, GB4542 showed enhanced Ab-dependent cellular cytotoxicity, Ab-dependent cellular phagocytosis, and complement-dependent cytotoxicity compared with GB4500. However, at higher concentrations, an Fc analog of GB4542 inhibited anti-CD20 mAb–mediated B cell clearance through direct blocking of both Fc–FcγR interactions and C1q deposition on target cells. Furthermore, the higher-order multimer fraction of GB4542 demonstrated greater binding avidity with the canonical FcγRs and was associated with inhibitory effects observed in Ab-dependent cellular phagocytosis and complement-dependent cytotoxicity assays. These data suggest that GB4542 might have utility in the treatment of autoimmune diseases by combining both mAb-mediated B cell depletion and multimerized Fc-mediated tolerogenic effects.

show abstract

Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

Cited by 343 publications

References 51 publications

Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study

Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study

Off‐Trial Evaluation of the B cell–Targeting Treatment in the Refractory Cases of Antineutrophil Cytoplasmic Antibodies (ANCA)‐Associated Vasculitis: Long‐Term Follow‐Up from a Single Centre

Anti-CD20 Antibody with Multimerized Fc Domains: A Novel Strategy To Deplete B Cells and Augment Treatment of Autoimmune Disease

Contact Info

Product

Resources

About