title: Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy.
abstract: Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty-six patients with established erosive RA non-responding to combination treatment with DMARDs and TNF-alpha inhibitors were treated with anti-CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin-producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12-58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow-up, B cells returned to circulation in 86% of patients. Fifty-three percent of the patients were successfully retreated with rituximab or re-started with anti-TNF-alpha treatment. Of the 11 non-responders, five were retreated with anti-CD20 within 2 months, four of them with success, four patients received TNF-alpha inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF-alpha inhibitors may be effectively treated with anti-CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Göteborg, Sweden. maria.bokarewa@rheuma.gu.se
authors.forename: M
authors.initials: M
authors.lastname: Bokarewa
authors.forename: C
authors.initials: C
authors.lastname: Lindholm
authors.forename: K
authors.initials: K
authors.lastname: Zendjanchi
authors.forename: M
authors.initials: M
authors.lastname: Nadali
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D018771:Arthralgia / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001799:Blood Sedimentation / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D004351:Drug Resistance; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D010976:Platelet Count; D012213:Rheumatic Fever / Q000097:blood / Q000276:immunology* / Q000628:therapy; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D006454:Hemoglobins; D007136:Immunoglobulins; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D008727:Methotrexate