Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: clues for the pathogenesis.

Abstract

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 TNFα 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.

• Authors: Gianfranco Ferraccioli, Barbara Tolusso, Francesca Bobbio-Pallavicini, Elisa Gremese, Viviana Ravagnani, Maurizio Benucci, Edoardo Podestà, Fabiola Atzeni, Alice Mannocci, Domenico Biasi, Mariangela Manfredi, Piercarlo Sarzi-Puttini, Bruno Laganà, Carlomaurizio Montecucco
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e40362 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22859946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antirheumatic Agents
• Autoantibodies
• B-Cell Activating Factor
• Biomarkers
• IL6 protein, human
• Interleukin-6
• TNFSF13B protein, human
• Rituximab

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Area Under Curve
• Arthritis, Rheumatoid (blood, immunology, therapy)
• Autoantibodies (blood)
• B-Cell Activating Factor (blood)
• B-Lymphocytes
• Biomarkers (blood)
• Female
• Humans
• Interleukin-6 (blood)
• Logistic Models
• Lymphocyte Depletion
• Male
• Middle Aged
• ROC Curve
• Retrospective Studies
• Rituximab
• Severity of Illness Index
• Treatment Outcome