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Competing Interests: The authors declare no conflict of interest.

Objective: The objective of this study was to assess the SARS-CoV-2-specific humoral and T cell response after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA)., Methods: In this observational study, patients with RA who are ≥18 years of age and vaccinated for SARS-CoV-2 according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies (ELISA-COVIDAR test), neutralizing activity (cytotoxicity in VERO cells), and specific T cell response (IFN-γ ELISpot Assay) were assessed after the first and second dose., Results: A total of 120 patients with RA were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), and BBIBP-CorV (22.5%). The most frequent combination was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose, 81.7% presented with anti-SARS-CoV-2 antibodies, 70.0% presented with neutralizing activity, and 65.3% presented with specific T cell response. The use of BBIBP-CorV and treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses. BBIBP-CorV was also associated with the absence of T cell response. The total incidence of adverse events was 357.1 events per 1,000 doses, significantly lower with BBIBP-CorV (166.7 events per 1,000 doses, P < 0.02)., Conclusion: In this RA cohort vaccinated with homologous and heterologous regimens against COVID-19, 2 out of 10 patients did not develop anti-SARS-CoV-2 IgG, 70% presented with neutralizing activity, and 65% presented with specific T cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, whereas treatment with ABA and RTX resulted in an impaired anti-SARS-CoV-2 IgG formation and neutralizing activity., (© 2023 American College of Rheumatology.)

Objective: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses., Methods: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose., Results: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03)., Conclusion: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response., (Copyright © 2022 by the Journal of Rheumatology.)

Objectives: To evaluate the adherence to treatment with Tofacitinib in patients with Rheumatoid Arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to Tofacitinib and to compare the performance of both questionnaires., Material and Methods: A cross-sectional study was carried out. We included patients ≥18 years old, with RA (ACR/EULAR criteria 2010) under treatment with Tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5., Statistical Analysis: Descriptive statistics. t-Test or Mann Whitney to compare the continuous variables, Chi 2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression., Results: We included 52 patients, 82.7% women, with a median (m) age of 57.7 years, disease duration m 16 years, 63.5% had comorbidities. Of the patients, 86.5% were treated with Tofacitinib (5 mg BID) and 48% received Tofacitinib as monotherapy. The median time of Tofacitinib treatment was 13 months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5% and 84.6% had an adherence ≥ 80%. The variables significantly associated with adherence ≥ 80% were the presence of comorbidities (p = .014) and older age (p = .033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment., Conclusions: Treatment adherence to Tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: To evaluate the adherence to treatment with tofacitinib in patients with rheumatoid arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to tofacitinib and to compare the performance of both questionnaires., Material and Methods: A cross-sectional study was carried out. We included patients ≥18years old, with RA (ACR/EULAR criteria 2010) under treatment with tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5., Statistical Analysis: Descriptive statistics. T-test or Mann Whitney to compare the continuous variables, chi 2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression., Results: We included 52 patients, 82.7% women, with a median (m) age of 57.7years, disease duration m 16years, 63.5% had comorbidities. Of the patients, 86.5% were treated with tofacitinib (5mg BID) and 48% received tofacitinib as monotherapy. The median time of tofacitinib treatment was 13months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5%, and 84.6% had an adherence ≥80%. The variables significantly associated with adherence ≥80% were the presence of comorbidities (P=.014) and older age (P=.033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment., Conclusions: Treatment adherence to tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objective: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries., Methods: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs., Results: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016., Conclusion: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) in the CONAART database (Argentine Consortium for Early Arthritis) were assessed for genetic risk factors for RA, specifically for HLA-DRB1 alleles and the PTPN22 rs2476601 polymorphism associated with progression to RA. This is a case-control study. Blood samples were obtained to determine HLA-DRB1 genotypes by PCR-SSO Luminex and PTPN22 (rs2476601) polymorphism by allelic discrimination. A control group of individuals from the general Argentinian population were obtained from the national register of cadaveric organ donors. A total of 1859 individuals were included in this analysis: 399 patients from the CONAART database (347 patients with RA at study end and 52 patients with UA at study end, mean follow-up time 25 ± 18 months) and 1460 individuals from the general Argentinian population. Compared with the controls, the HLA-DRB1*04 and DRB1*09 alleles were more commonly detected in patients with RA diagnosis (OR (95% CI) 2.23 (1.74-2.85) and 1.89 (1.26-2.81)) respectively. Both patients with UA and the general population showed higher frequency of DRB1*07, DRB1*11 and DRB1*15 alleles than patients with RA. PTPN22 rs2476601 polymorphism frequency was higher in RA and UA vs the general population; however, this was significantly different only for RA vs control group (OR [95% CI] = 1.81 [1.10-3.02], P = 0.018. HLA-DRB1 typing and PTPN22 allelic discrimination could distinguish between patients with UA, patients with early RA, and the general population in Argentina. This is the first study of HLA-DRB1 alleles and PTPN22 polymorphism associations with progression to early RA in an Argentinian population.

Objective: The blockade of inflammatory mediators produced by biological therapies is associated with an increased risk of opportunistic infections, as for example Mycobacterium tuberculosis (MT). Given the endemic situation of tuberculosis (TB) in some countries and immunosuppression/anergy of patients with chronic inflammatory arthritis, we wonder whether it is necessary to monitor the MT infection after starting the biological treatment. To evaluate the frequency of the tuberculin skin test (TST) conversion and its association with an active TB infection and other disease variables., Methods: Patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and spondyloarthritis (SpA) receiving treatment with anti-TNF, tocilizumab, and/or abatacept agents were included into the study. Patients had to have a negative TST (<5 mm) at the baseline, and a second TST was performed 2-22 months after the initiation of biologic therapy. The TST conversion was considered as a variation ≥5 mm between the two TSTs performed within an interval between 2 months and 2 years., Results: A total of 85 patients were included into the study, and 78.8% were women, with a median schooling duration of 12 years. A total of 74.1% of patients had RA, 16.5% psoriatic arthritis, and 4.7% AIJ and ankylosing spondylitis. Regarding treatment, 75.3% received anti-TNF therapy (31.8% etanercept, 21.2% adalimumab, 17.6% infliximab, 3.5% golimumab, and 1.2% certolizumab), 15.3% tocilizumab, and 9.4% abatacept. Eight patients (9.4%) developed a TST conversion. The shift was more frequent in men (62.5%) than in women (37.5%) (p=0.009), and in those with a prolonged disease duration (X 226±109 vs X130±105 [p=0.017]). This association remained after adjusting for other variables. All patients who developed a TST conversion received prophylactic isoniazid, and only one patient with other risk factors developed active TB., Conclusion: The frequency of a TST conversion in patients with chronic inflammatory arthritis was low and was associated with male gender and longer disease duration.

The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the "magic bullet".