Biomarkers of Good EULAR Response to the B Cell Depletion Therapy in All Seropositive Rheumatoid Arthritis Patients: Clues for the Pathogenesis

被引:31
作者
Ferraccioli, Gianfranco [1 ]
Tolusso, Barbara [1 ]
Bobbio-Pallavicini, Francesca [2 ]
Gremese, Elisa [1 ]
Ravagnani, Viviana [3 ]
Benucci, Maurizio [4 ]
Podesta, Edoardo [5 ]
Atzeni, Fabiola [6 ]
Mannocci, Alice [7 ]
Biasi, Domenico [3 ]
Manfredi, Mariangela [4 ]
Sarzi-Puttini, Piercarlo [6 ]
Lagana, Bruno [5 ]
Montecucco, Carlomaurizio [2 ]
机构
[1] Univ Cattolica Sacro Cuore, Div Rheumatol, I-00168 Rome, Italy
[2] Univ Pavia, IRCCS S Matteo Fdn, Div Rheumatol, I-27100 Pavia, Italy
[3] Univ Verona, Sect Rheumatol & Internal Med, Dept Clin & Expt Med, I-37100 Verona, Italy
[4] Osped S Giovanni di Dio, Dept Internal Med, Rheumatol Unit, Florence, Italy
[5] Univ Roma La Sapienza, S Andrea Univ Hosp, Sch Med 2, Div Clin Immunol & Rheumatol, Rome, Italy
[6] Univ Hosp L Sacco, Rheumatol Unit, Milan, Italy
[7] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Unit Hyg, Rome, Italy
关键词
RITUXIMAB TREATMENT; DISEASE-ACTIVITY; TNF AGENTS; REMISSION; STEP; METHOTREXATE; MONOTHERAPY; MEDICINE; EFFICACY; CRITERIA;
D O I
10.1371/journal.pone.0040362
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Objective: To find out whether a high number of auto-antibodies can increase the probability of a "good-EULAR response'' and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT). Patients and Methods: One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNF alpha blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined. Results: At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count, <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count. Discussion: The number of AABs increased the chances of being a "good-EULAR'' responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables - no steroids and lymphocyte count - and two laboratory assays - IgG-RF and BAFF.
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