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.

Figure 1. Percentage of good and moderate EULAR response rate (%) in RA patients after 6 months of RTX therapy.

Patients were grouped according to the number of fulfilled parameters (corticosteroids therapy, number of circulating lymphocytes <1875/μl, plasma BAFF levels <1011 pg/ml and RF-IgM >52.1 U/ml). Good response was reached in 20.8% of RA patients that fulfilled 0–1 parameter, in 29.2% of subjects that fulfilled 2–3 parameters and in 54.5% of subjects that fulfilled 4 parameters (Fisher's exact test between 4 parameters and 0–3 = 0.08). Moderate-response was reached in 41.7% of RA patients that fulfilled 0–1 parameter, in 54.5% of subjects that fulfilled 2–3 parameters and in 72.7% of subjects that fulfilled 4 parameters (χ2 test = 3.02, df = 2; p = 0.22). *p = 0.046: percentage of good response in patients fulfilling 4 vs 0–1 parameters.