OBJECTIVES:To compare the effectiveness, safety, and retention of rituximab biosimilar (RTX-GP2013) and RTX-originator in RTX-naive Rheumatoid Arthritis (RA) patients in a real-world setting. METHODS:This single-center, longitudinal, observational study included 107 RA patients who initiated RTX therapy between January/2010 and September/2023 (40 RTX-GP2013 and 67 RTX-originator). A convenience sample of consecutive eligible RTX-naïve patients was analyzed. Disease activity, treatment retention, and infusion-related reactions were assessed over six months (6M). Multivariate logistic regression identified predictors of low disease activity (CDAI ≤ 10) at 6M. RESULTS:RTX-GP2013 patients were older (58.3 [53.1-66.4] vs. 54.9 [45.6-60.8], p = 0.029), had longer disease duration (18.4 ± 9.5 vs. 14.7 ± 8.9, p = 0.045), and a greater number of prior biologic therapies (3 [1-5] vs. 1 [0-2], p < 0.001). At 6M, frequency of low disease activity (30.0% vs. 47.8%, p = 0.103), retention rates for a second RTX cycle (77.5% vs. 85.1%, p = 0.433) and mild/moderate infusion-related reactions (17.5% vs. 9.0%, p = 0.231), were comparable between RTX-GP2013 and RTX-originator groups, respectively. Multivariate analysis identified lower baseline disease activity (per 1-point increase in CDAI: OR = 0.93, 95% CI 0.88-0.97, p = 0.003) and fewer prior advanced therapies (OR = 0.56, 95% CI 0.38-0.82, p = 0.003) as predictors of low disease activity at 6M, whereas RTX-GP2013 was not associated with poorer clinical response (OR = 1.85, 95% CI 0.63-5.45, p = 0.265). CONCLUSION:In this real-world study, RTX-GP2013 and RTX-originator demonstrated comparable effectiveness, safety, and treatment retention in RTX-naive RA patients. Baseline disease activity and fewer prior therapies were predictors of clinical response. These findings reinforce the role of biosimilars in expanding access to effective therapies while maintaining clinical outcomes.

The increasing availability of biosimilars has raised important questions regarding their interchangeability with originator biologics in the treatment of immune-mediated rheumatic diseases. Addressing this issue is critical to ensuring patient safety, therapeutic efficacy, and informed clinical decision-making. To present a position statement from the Biotechnology Committee of the Brazilian Society of Rheumatology on the interchangeability between originator and biosimilar biologic drugs in rheumatologic care. A task force of 22 rheumatologists with expertise in immunobiological therapies followed a structured three-phase consensus process: (1) development of five key questions on biosimilar interchangeability; (2) comprehensive literature review using MEDLINE, EMBASE, and LILACS databases; and (3) final review and endorsement by relevant BSR committees. Expert opinion was used when evidence was limited or inconclusive. The position statement comprises five consensus-based recommendations, all unanimously supported by the task force, and supported by current scientific evidence and clinical experience. The Biotechnology Committee of the Brazilian Society of Rheumatology endorses the safe and effective interchangeability of originator and biosimilar biologics when guided by principles that ensure patient safety, therapeutic continuity, and healthcare system sustainability. Not applicable.

PT005 / #801 Topic: AS17 - Miscellaneous POSTER TOUR 01: CLINICAL OUTCOMES IN SLE 22-05-2025 10:00 AM - 10:40 AM Patients with autoimmune rheumatic diseases (ARDs) are at high risk of herpes zoster (HZ) and the new recombinant vaccine against HZ (RZV) offers safety improvements. This study evaluates disease safety, overall safety and humoral immunogenicity of RZV in ARD patients compared to nonvaccinated ARDs and nonimmunosuppressed control group (CG). This prospective double-blind randomized placebo-controlled phase 4 study evaluated ARD patients at high risk of HZ. Participants aged >18 years were randomized into 2 groups: P1 (vaccine) and P2 (placebo), with nonimmunosuppressed individuals serving as CG. Both P1 and CG received 2 intramuscular doses of RZV administered 6 weeks apart (D0 - V1 and D42 - V2), while P2 received placebo. Disease activity was evaluated using specific scores and adverse events (AEs) were assessed through a standardized questionnaire. Blood samples were collected prior to the 1st dose (V1) and 6 weeks following the 2nd dose (V3) with humoral immunogenicity measured via anti-gE antibody serum concentrations (ELISA). A total 1,012 ARD patients (P1:529 and P2:483) and 393 CG completed the study. ARDs included 9 different chronic conditions, mainly rheumatoid arthritis (n = 290) and systemic lupus erythematosus (n = 302). At baseline, treatments included prednisone (39%), hydroxychloroquine (31%), sulfasalazine (6%), immunosuppressive drugs (79%) [mycophenolate mofetil (24%), methotrexate (23%), leflunomide (20%), azathioprine (18%) and cyclosporine (2%), tacrolimus (2%) and cyclophosphamide (3%)], biologic therapy (44%) [TNFi (17%), tocilizumab (8%), rituximab (7%), belimumab (6%), secukinumab (5%) and anifrolumab (1%)] and JAK inhibitors (4%). P1(vaccine) and P2 (placebo) groups were balanced for age [50 (IQR 39.8 - 61) vs 51 (IQR 40 - 61.8) years, p = 0.543], female sex (77% vs 80%, p = 0.314), ARD diagnoses and therapies (p > 0.05), except for lower frequency of mycophenolate mofetil (MMF) in P1 (p = 0.047). The primary endpoint showed comparable flare frequencies in P1 and P2 at V2 (4.1% vs 6.2%, p = 0.142) and V3 (10.2% vs 11.6%, p = 0.506). Secondary endpoints revealed no moderate/severe AEs, but AEs were less frequent in P1 (78% vs 90%, p < 0.0001), including both local (72% vs 85% p < 0.0001) and systemic reactions (50% vs 62%, p = 0.001), mainly headache (24% vs 33%, p=0.005), fatigue (16% vs 24%, p = 0.008), drowsiness (16% vs 23%, p = 0.015), myalgia (16% vs 21%, p = 0.034), chills (15% vs 21%, p = 0.012) and fever (11% vs 19%, p=0.002) after 1st RZV dose. Although humoral response was adequate, it was lower in P1 compared to CG (92% vs 99%, p < 0.0001). Baseline GMT was similar (p = 0.674), but the GMT increase after 2 doses was lower in P1 than in CG [35.09 (95%CI 30.49-40.4) vs 64.52 (95%CI 55.97-74.38); p < 0.001]. Multivariate analysis identified rituximab [OR 0.152 (95%CI 0.059-0.393), p < 0.0001] and MMF [OR 0.0460 (95%CI 0.224-0.946), p = 0.035] as major deleterious factors for reduced vaccine response. No HZ case were confirmed by RT-PCR up to week 12. RVZ demonstrated a strong disease safety profile and adequate short-term immunogenicity in highly immunosuppressed ARD patients, including those with active diseases, with no severe adverse events and no significant impact on disease activity. Our findings highlight MMF and rituximab as key factors impairing vaccine immunogenicity, suggesting that a booster dose may be beneficial for patients on these therapies.

Patients with autoimmune rheumatic diseases (ARDs) are at an increased risk for herpes zoster (HZ). Vaccination is recommended for this population. The aim of this study was to evaluate the safety of vaccination with the recombinant zoster vaccine (Shingrix) in ARD patients, humoral immunogenicity (HI), cellular immunogenicity (CI), and the incidence of HZ. This randomized, double-blind, placebo-controlled phase 4 study involves 1180 ARD patients and a control group (CG) of 393 balanced healthy individuals, aged ≥50 years. ARD patients will be randomly assigned in a blinded manner (1:1 ratio) to 2 groups: vaccine or placebo (on days 0 and 42), administered intramuscularly. Outcomes will be assessed at baseline, 6 weeks, and 12 weeks after vaccination, including disease activity (using specific disease activity scores), HI, and CI. Adverse events will be assessed using a standardized questionnaire after each vaccine dose. Incident HZ cases will be monitored throughout the study. One year following the second dose, the persistence of HI and CI will be evaluated in both ARD patients and CG. HI and CI will be assessed using serum concentrations of anti-gE antibodies and the frequencies of gE-specific CD4+ T cells, respectively. Comparisons of anti-gE titers between ARD patients and CG at different time points will be analyzed using 2-way repeated-measures analysis of variance. Multiple regression analysis will be conducted, with a positive immune response as the dependent variable, and variables with p < 0.2 from univariate analysis as independent variables. This large trial addresses a critical gap by examining disease safety, efficacy, adverse effects, and immunogenicity, considering the impact of diverse therapies following recombinant zoster vaccine administration in ARD patients.

Aim: The use of anti-TNF drugs is well-established for treating axial spondyloarthritis (axSpA). The introduction of biosimilars offers a more accessible alternative, but data on the switching of adalimumab biosimilars in the axSpA population remain somewhat controversial and are limited to SB5 and ABP 501 and to the European population. This study aims to evaluate the clinical efficacy of switching from originator adalimumab to the biosimilar adalimumab-AACF in Latin American axSpA patients over a 12-month period in a real-life analysis. Methods: This observational study included patients with axSpA who had been treated with originator adalimumab for at least three months and switched to the biosimilar. Disease activity parameters and C-reactive protein (CRP) levels were assessed at baseline (T0) and compared at 6 (T6) and 12 months (T12) following the switch. Results: Twenty-eight patients were included, with a mean duration of originator adalimumab use of 87.6 months. Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP remained stable when comparing T0 to T6 [1.56 (± 0.88) vs. 1.50 (± 0.82), P = 0.73] and T12 [1.56 (± 0.88) vs. 1.26 (± 0.86), P = 0.13]. A similar pattern was observed for ASDAS-erythrocyte sedimentation rate (ESR; P > 0.05) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; P > 0.05). The rate of remission/low disease activity was consistent, recorded at 71.4% at baseline, 78.6% at T6 (P = 0.62) and 78.6% at T12 (P = 0.68). CRP levels did not show significant variation (P > 0.05) across time points. Notably, the one-year drug retention rate was 94.6%. Conclusions: This real-world study highlights for the first time the feasibility and efficacy of transitioning from originator adalimumab to biosimilar AACF in axSpA, providing support for its use in long-term management and offering enhanced accessibility without compromising therapeutic outcomes. These results add valuable Latin American data to the body of evidence on biosimilar integration into clinical practice.

Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

BACKGROUND:The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil.AIM:To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database.METHODS:This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence.RESULTS:From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population.CONCLUSIONS:Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

Temporary interruption of methotrexate(MTX) for 2 weeks after vaccination enhances the immunogenicity of influenza and COVID-19 vaccines, especially in older patients.However, the protocol has also been associated with increased flare rates in rheumatoid arthritis(RA).This study aims to investigate the influence of age on the immunogenicity and identify predictors of flare in the 2-week MTX interruption protocol.

Patients with rheumatoid arthritis(RA) are more prone to severe COVID-19 due to immunosuppression and/or comorbidities.We aimed to verify the effectiveness of vaccination in reducing the severity of COVID-19 in a tertiary RA cohort and the profile of infected patients before and after vaccination.