B Cell Profile for Early Identification of Optimal Responders to TNF-inhibitors in Rheumatoid Arthritis

Cristina Sobrino¹, Borja Hernández-Breijo ², Carlota García-Hoz ³, Israel Nieto-Gañán ⁴, Victoria Navarro-Compán ⁵, Ana Martínez-Feito ⁶, javier Bachiller ¹, Gema Bonilla ⁷, Cristina Pijoán-Moratalla ¹, Paloma Lapuente-Suanzes ⁸, Dora Pascual-Salcedo ², Alejandro Balsa ⁷, Garbiñe Roy ⁴, Mónica Vázquez Díaz ¹, Luisa María Villar ⁴, Chamaida Plasencia ⁷ and Eulalia Rodríguez-Martín ⁴, ¹Rheumatology Department, Ramón y Cajal University Hospital & IRYCIS, Madrid, Spain, ²Immuno-Rheumatology Research Group, IdiPAZ. La Paz University Hospital, Madrid, Spain, ³Immunology Department, Ramón y Cajal University Hospital & IRYCIS, Madrid, ⁴Immunology Department, Ramón y Cajal University Hospital & IRYCIS, Madrid, Spain, ⁵University Hospital La Paz, IdiPaz, Madrid, Spain, ⁶Immuno-Rheumatology Research Group, IdiPAZ & Immunology Department. La Paz University Hospital, MADRID, Spain, ⁷Immuno-Rheumatology Research Group, IdiPaz & Rheumatology Department. La Paz University Hospital, Madrid, Spain, ⁸University Hospital Ramón y Cajal, Madrid

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: anti-TNF therapy, biomarkers and remission, Rheumatoid arthritis (RA)

Session Information

Date: Monday, November 11, 2019

Session Title: RA – Treatments Poster II: Established Treatments

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Rheumatoid arthritis (RA) is a chronic, inflammatory and heterogeneous autoimmune disorder of unknown etiology characterized by progressive joint damage. Although TNF inhibitors (TNFi) have contributed to change the natural history of RA, approximately 30-50% of patients do not respond to this therapy and only a maximum of 47% achieved clinical remission. The aim of this study was to investigate whether the blood immunological profile at baseline of patients with RA could contribute to predict clinical remission to TNFi.

Methods: This is a prospective bi-center pilot study including 98 patients with RA that initiated a TNFi therapy. Clinical activity was assessed at baseline and after 6 months of treatment by disease activity score 28 (DAS28), considering optimal response if patients reached remission (DAS28≤2,6). We obtained PBMC before treatment and different leukocyte subsets were evaluated by flow cytometry in a FACSCantoII instrument. Baseline characteristics of the patients included in the study were collected. All the analyses were adjusted by sex, anti-citrullinated peptide antibodies (ACPA), rheumatoid factor (RF), baseline-c reactive protein (CRP) and baseline-DAS28 through univariable and multivariate logistic regression models (odds ratio; 95% CI; p value).

Results: At 6 months of follow-up, 39% of patients reached remission by DAS28 (REM patients). Univariable analyses were performed to investigate the association between clinical remission and baseline variables: a significant association was found for positivity of RF, presence of ACPA, lower CRP and lower baseline DAS28. In the multivariate analysis, only lower baseline DAS28 (OR: 0.32; 95% CI: 0.18-0.56; p< 0.0001) remained independently associated with REM after 6m of treatment. Basal leukocyte profile clearly differentiated between REM versus no-REM patients. REM patients showed higher percentage of B cells (OR=1.19; 95%; CI:1.05-1.35; p=0.007) and naive B cells (Bn; OR=1,32; 95%; CI:1.08-1.61; p=0.007) than no-REM patients at baseline (Figure 1). The other PBMC subsets (monocytes, NK cells, CD4+ and CD8+ T cells subtypes) did not show statistical differences.

Conclusion: Our results suggest that B cell profile would be the group of determinant cells to organize the response to TNFi in patients with RA. Further studies are necessary for a better understanding of the biological meaning of the increase in the naive B cells in REM patients.

figure1

Figure 1. Association between the percentage of PBMC subset before TNFi therapy and the clinical remission. Logistic regression analysis was performed for each PBMC subset. The percentage of total B cells and in naïve B cells were independently associated with the clinical response. No association was found in other PBMC subsets. The analyses were adjusted by sex, ACPA, RF, baseline-CRP and baseline-[DAS28].

Disclosure: C. Sobrino, None; B. Hernández-Breijo, None; C. García-Hoz, None; I. Nieto-Gañán, None; V. Navarro-Compán, AbbVie, 5, 8, Bristol, 8, Bristol, Roche, 8, Eli Lilly and Company, 5, 8, Eli Lilly, Novartis, Abbvie, UCB, MSD, 5, 8, MSD, 5, 8, Novartis, 5, 8, Pfizer, 5, Roche, 8, UCB, 5, 8; A. Martínez-Feito, None; j. Bachiller, None; G. Bonilla, None; C. Pijoán-Moratalla, None; P. Lapuente-Suanzes, None; D. Pascual-Salcedo, PFIZER, 5, ABBVIE, 5, TAKEDA, 5, MENARINI, 5, GRIFOLS, 5; A. Balsa, BMS, 2, Roche Pharma, 2; G. Roy, None; M. Vázquez Díaz, None; L. Villar, None; C. Plasencia, None; E. Rodríguez-Martín, None.

To cite this abstract in AMA style:

Sobrino C, Hernández-Breijo B, García-Hoz C, Nieto-Gañán I, Navarro-Compán V, Martínez-Feito A, Bachiller j, Bonilla G, Pijoán-Moratalla C, Lapuente-Suanzes P, Pascual-Salcedo D, Balsa A, Roy G, Vázquez Díaz M, Villar L, Plasencia C, Rodríguez-Martín E. B Cell Profile for Early Identification of Optimal Responders to TNF-inhibitors in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/b-cell-profile-for-early-identification-of-optimal-responders-to-tnf-inhibitors-in-rheumatoid-arthritis/. Accessed July 2, 2020.

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