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FRI0037 Clinical and B Cell Subsets Biomarkers of Response to Tocilizumab in Rheumatoid Arthritis
  1. E. Gremese,
  2. B. Tolusso,
  3. A.L. Fedele,
  4. M. Nowik,
  5. S. Canestri,
  6. G. Ferraccioli
  1. Division Of Rheumatology, Institute Of Rheumatology And Affine Sciences, Catholic University Of The Sacred Heart, Rome, Italy

Abstract

Background Tocilizumab (TCZ) is effective in the treatment of Rheumatoid Arthritis (RA) and it is recognized as a modifier of B cell subsets in vivo, inducing changes over time in the distribution of B cell subpopulation, i.e. regulatory TGF+ B cells and memory B cells.

Objectives To define whether the combination of clinical variables (sex, disease duration, BMI, seropositivity, DAS value) and B cell subsets analysis at baseline could help to define the best responders and to see whether changes after 3 months could predict the occurrence of DAS remission at 3 and 6 months.

Methods 62 consecutive RA patients (75.8% female, average age: 52.9±15.3 years, average disease duration: 8.8±10.4 years, 64.5% ACPA+ and/or IgM-RF+ and 48.4% overweight or obese) who initiated TCZ (8 mg/kg monthly) were recruited. All patients were no responders to conventional disease modifying antirheumatic drugs (DMARDs), including methotrexate, and biologic agents (b-DMARDs; 46.8%). At baseline and every 3 months demographic and immunological data and the ACR/EULAR core data set [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), swollen joint count (SJC), tender joint count (TJC), physician and patient global assessment, pain, health assessment questionnaire (HAQ)] were recorded. At each visit, clinical improvement and remission were evaluated according to DAS (DAS-R). At baseline and at 6-month follow-up visit peripheral blood samples were collected and analyzed by flow cytometry for the distribution of circulating B cell subsets using IgD/CD27 classification.

Results Mean DAS at baseline was 3.7±0.9. A DAS-R was reached in 28.3% of RA patients at 3 months (T3), 39.7% at 6 months (T6) and 51.0% at 12 months (T12) follow-up. Fifty percent of the ERA patients already had DAS-R compared to 20.5% of LSRA (p=0.03) at T3. The percentage of DAS-R at 3 and 6 months FU was lower in female patients (17.8% at T3 and 29.5% at T6) compared to male patients (60% at T3, p=0.002 and 71.4% at T6, p=0.01) but at T12 the difference was not significant (45.0% vs 72.7%, p=0.11). RA patients with baseline DAS<3.7 reached DAS-R at T3 in 40.6% whereas those with DAS>3.7 reached DAS-R in 14.3% (p=0.02). At T12 the percentages were 64.5% vs 36% (p=0.04), respectively. Being RF and/or ACPA seropositive or having a different BMI, did not influence the outcome at T3 as well as at T6 or at T12. Finally, being smokers predicted a better response at T3 than never-smokers (p=0.02). Considering the B cell subsets, a higher frequency of switched-memory B cells (IgD-CD27+; >20.8%) was associated with DAS-R at T3 (p=0.04) and T6 (p=0.11). This finding was confirmed by the inverse correlation between IgD-CD27+ cell percentages at baseline with DAS value at T3 (R=-0.270; P=0.04) and T6 (R=-0.310; P=0.02).

Conclusions In our RA cohort, being male, having DAS<3.7, being ERA represents the best matrix to predict DAS remission at 3 and 6 months.

Disclosure of Interest None declared

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