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- Hernández-Breijo, Borja, et al.
(författare)
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BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.
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| 2. |
- Hernández-Breijo, Borja, et al.
(författare)
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Low Serum BAFF Concentration Is Associated with Response to TNF Inhibitors in Seropositive Patients with Rheumatoid Arthritis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:17
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Tidskriftsartikel (refereegranskat)abstract
- We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months of treatment was defined according to the EULAR criteria for good responders (GRs). BAFF concentration was measured in serum samples, collected at baseline and at 6 months. Associations with EULAR response were evaluated using univariable and multivariable logistic regression models. ROC analysis was performed to determine the optimal threshold of serum BAFF concentration associated with good EULAR response to treatment. After 6 months of TNFi treatment, 24% of patients were GRs. They had a lower BMI, lower baseline DAS28 and lower baseline serum BAFF concentration than non-responders. After 6 months of TNFi treatment, autoantibody-positive patients who attained GR had significantly lower serum BAFF concentrations compared with patients who did not. Serum BAFF < 968 pg/mL at 6 months represented the concentration likely to best discriminate between GR and non-GR at 6 months of TNFi treatment. Autoantibody-seropositive patients who had serum BAFF < 968 pg/mL at 6 months demonstrated a more than four-fold increased probability to be GRs compared with patients with higher BAFF concentrations. In conclusion, serum BAFF concentrations were associated with response to TNFis in seropositive RA patients, corroborating the importance of the B-cell compartment in RA.
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| 3. |
- Hernandez-Breijo, Borja, et al.
(författare)
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Serum B Cell Activating Factor Reflects Good EULAR Response to TNF Inhibition in Patients with Rheumatoid Arthritis
- 2021
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2586-2588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: The latest breakthroughs in the pathophysiology of rheumatoid arthritis (RA) highlighted the activation of B cells as a trigger of the joint flare initiation and therefore, implicated a central role for B cells in RA pathogenesis. B cell activating factor (BAFF) is essential for B cell activation, differentiation and survival. The main objective of this study was to investigate the role of BAFF in the progression of rheumatoid arthritis during treatment with TNF inhibitors (TNFi) and its association with treatment response.Methods: This was a prospective study including 158 patients with RA initiated at the first TNFi and followed- up for 6 months (m). Disease activity was assessed using the Disease Activity Score 28 (DAS28) at baseline and 6m of treatment. Clinical response at 6m of treatment was defined according to the EULAR criteria for good responders. BAFF concentration was measured in serum samples collected at baseline and 6m. Associations between the EULAR response at 6m and clinical/serological variables were evaluated using univariable and multivariable logistic regression models. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of serum BAFF concentration portending EULAR response at 6m of TNFi treatment, determined as the highest Youden index.Results: After 6m of TNFi treatment, 38/158 (24%) of patients attained good EULAR response (GR). These patients had lower body mass index (BMI) (p=0.02), lower baseline DAS28 (p=0.02) and lower serum BAFF concentration at baseline and at 6m compared with patients who did not attain GR. To further investigate the role of BAFF, the cohort was stratified by anti- citrullinated protein antibody (ACPA) seropositivity. 134 (85%) patients were ACPA positive and 24 (15%) were seronegative. After 6m of TNFi treatment, seropositive patients who attained GR had lower serum BAFF concentration compared with patients who did not attain GR (median [IQR]: 793 [712- 956] pg/mL vs. 955 [808- 1176] pg/mL; p=0.006) (Figure 1). However, there were no differences in ACPA negative patients (Table 1). Therefore, the optimal threshold value for serum BAFF concentration associated with GR at 6m of TNFi treatment was evaluated in seropositive patients. Serum BAFF< 968 pg/mL at 6m represented the concentration likely to best discriminate between GR and non- GR at 6m of TNFi treatment (AUC: 0.67; 95% CI: 0.56- 0.78; p=0.009; sensitivity: 50%, specificity: 81%; PPV: 89%, NPV: 35%), yielding a positive likelihood | 2587ratio of 2.7 (Figure 2). Then, a logistic regression analysis adjusted by patient characteristics with p- value≤0.1 in univariable analysis (disease duration, BMI and baseline DAS28) was performed. We found that a serum BAFF< 968 pg/mL at 6m was significantly and independently associated with GR attainment in seropositive patients (OR: 5.28; 95% CI: 1.72- 16.17; p=0.004).Conclusion: Our results show that serum BAFF concentrations reflect clinical response to TNFi after 6m of treament, mainly in ACPA positive patients. These results suggest that BAFF may be considered a biomarker of clinical re-sponse to TNFi in patients with RA.
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