Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Síndrome de Behçet, para atualização médica.
A newsletter discute a alta prevalência de manifestações cardíacas na Síndrome de Behçet, frequentemente subestimada e associada à atividade sistêmica da doença. O conteúdo também aborda a importância do rastreio de HPV em pacientes imunossuprimidos e apresenta a LBFSS, a primeira escala específica para mensurar a disfunção cognitiva no Lúpus.
A newsletter destaca o estudo RESET-RA, que apresenta a estimulação do nervo vago como uma alternativa promissora para pacientes com Artrite Reumatoide de difícil tratamento. São detalhadas as atualizações das diretrizes EULAR 2025, que reforçam o uso precoce de anti-TNF na Síndrome de Behçet e simplificam o manejo da Artrite Reumatoide após falha ao metotrexato. O conteúdo ainda aborda um caso clínico de tuberculose óssea e revisões rápidas sobre fibromialgia e gota.
Objective To evaluate comparative effectiveness of cyclosporine, interferon alfa‐2a, and adalimumab for the prevention of uveitis relapse in Behçet disease in real‐world settings. Methods We emulated a target trial involving adult patients with Behçet disease uveitis who initiated cyclosporine, interferon alfa‐2a, or adalimumab between April 10, 2008, and August 1, 2024, and were observed up until September 10, 2024. We applied overlap weighting to balance patient characteristics across treatment groups and emulate randomization at baseline. The primary outcome was the annualized relapse rate of uveitis during treatment with study therapy. Results The cohort comprised 716 cyclosporine users, 193 interferon alfa‐2a users, and 103 adalimumab users. The estimated mean annualized relapse rate of uveitis was 0.95 (95% confidence interval [CI] 0.82–1.10) with cyclosporine, 0.52 (95% CI 0.40–0.69) with interferon alfa‐2a, and 0.28 (95% CI 0.19–0.43) with adalimumab. Patients treated with cyclosporine experienced more relapses than those treated with adalimumab (incidence rate ratio [IRR] 3.36 [95% CI 2.23–5.05]; mean difference 0.66 [95% CI 0.48–0.85]; P < 0.001) or interferon alfa‐2a (IRR 1.81 [95% CI 1.37–2.4]; mean difference 0.42 [95% CI 0.22–0.62]; P < 0.001). The relapse rate was higher with interferon alfa‐2a than with adalimumab (IRR 1.86 [95% CI 1.16–2.97]; mean difference 0.24 [95% CI 0.05–0.43]; P = 0.011). Conclusion In Behçet disease, interferon alfa‐2a was associated with a reduction in uveitis relapse compared with cyclosporine, whereas adalimumab demonstrated a stronger association with reduced relapse than interferon alfa‐2a. image
Objective Phenotypic diversity of autoimmune diseases presents an ongoing diagnostic and therapeutic challenge. The discovery of mutations in RELA (encoding RELA/p65) in patients with diverse disease phenotypes suggests heterogeneous pathophysiologic mechanisms are at play, which may explain the observed phenotypic diversity. We identified seven novel/rare RELA variants in patients with autoimmune diseases and examined the functional consequences on immune signaling. Methods Whole‐exome sequencing analysis revealed seven novel/rare RELA variants. Following ectopic expression of wild type (WT) and mutant RELA proteins in HEK293 cells, NF‐ κ B/interferon‐ β (IFNβ) luciferase reporter assays were used to determine transcriptional activity. RELA expression was also assessed in transfected HEK293 cells and in patient peripheral blood mononuclear cells (PBMCs) via Western blot. NF‐ κ B and interferon‐stimulated genes in patient PBMCs were assessed via quantitative polymerase chain reaction following toll‐like receptor (TLR) activation. Results RELA I250V , RELA R295H and RELA E3* displayed a loss in NF‐κB transcriptional activity. RELA I250V and RELA R295H induced hyperactivation of the IFNβ promoter. Comparative to RELA WT , ectopically expressed RELA I250V protein levels were reduced. Collectively, an elevated IFN gene signature was not detected in patient PBMCs following TLR activation, however the patient heterozygous for I250V had elevated IFNβ transcripts after TLR7/8 activation. Conclusion We expand upon the clinical syndromes linked to RELA dysfunction and uncover rare/novel variants that have distinct functional effects on gene transcription downstream of NF‐κB and IFNβ promoter elements. These findings reinforce an important role for RELA in a range of autoimmune and autoinflammatory diseases.
Beneficial results have been reported among patients with familial Mediterranean fever who switched from coated colchicine to compressed colchicine preparations due to inefficacy or intolerance. In this study, we aimed to assess whether this approach is also beneficial in patients with Behçet's syndrome (BS) with mucocutaneous and/or joint involvement who had an inadequate response to or were intolerant of coated colchicine preparations. We conducted a retrospective chart review of BS patients who switched to compressed colchicine preparation between 2017 and 2023. Endpoints were disease activity assessed by Behçet's Disease Current Activity Index (BDCAI), patients' and physicians' global perception of disease activity on a 10 cm visual analogue scale (VAS), and C-reactive protein (CRP) levels. Among the 45 patients [29 women (64.4%), mean age: 39.4 (14.4)], the reason for switch was inadequate response in 33 patients and adverse events in 12. Overall, 30 patients (65.2%) were still on the compressed colchicine preparation during a mean follow-up of 32.2 (27) months. Seven patients had discontinued the drug due to adverse events, and 6 patients due to inefficacy. Patients' global VAS scores [5.8 (2.3) vs 3.7 (3.3); P = 0.008] and physicians' global VAS scores [4.2 (2.1) vs 2.3 (2.7); P = 0.003] were significantly improved at the final visit, and CRP levels [7.2 (10.4) vs 3.6 (5.2); P = 0.039] and mean BDCAI scores [2.6 (1.10) vs 2.04 (1.24); P = 0.006] significantly decreased compared with baseline. Switching between colchicine preparations seems to be a safe and effective option for BS patients, providing good drug survival rates, patient and physician global scores, and activity scores.
Abstract Objectives Refractory manifestations of Behçet’s disease (BD) are commonly treated with TNF-α inhibitors; however, a subset of patients do not respond or are intolerant, prompting the need for alternative therapies. This study aimed to assess the real-life use, efficacy, and safety of non-TNF targeted biologic agents in BD. Methods Data were retrieved from the International AIDA Network Registry for BD. Patients who received any biological agent other than TNF-α inhibitors at any point during follow-up were included in the study. Clinical and demographic characteristics, prior treatments, and treatment responses at 3-, 6-, and 12-month follow-ups were collected. Results In total, 65 patients (36 female/29 male) with a mean age of 45.8 ± 13.3 years were included. Anakinra was the most frequently used agent (n = 31), 34.7% of patients with mucocutaneous, 73.3% with musculoskeletal, and 77.7% with ocular involvement showing a partial or complete response. Canakinumab (n = 11) was effective in mucocutaneous, musculoskeletal, and ocular involvement, including some previously unresponsive to anakinra. Tocilizumab (n = 15) showed favorable outcomes in ocular and neurological involvement (complete response in 5 of 6 patients), while 40% experienced worsening or no response in mucocutaneous manifestations. Secukinumab and ixekizumab were effective in patients with mucocutaneous-articular phenotypes, especially those with axial spondyloarthritis. Ustekinumab (n = 3) and rituximab (n = 5) also demonstrated clinical improvement in selected refractory cases. No new major safety concerns were reported across treatment groups. Conclusion Biologics targeting IL-1, IL-6, IL-17, and IL-12/23 pathways may offer therapeutic alternatives in BD patients unresponsive to TNF-α inhibitors. The treatment efficacy varies across phenotypes, highlighting the need for individualized treatment decisions.
Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation (LPO), is implicated in the pathogenesis of autoimmune diseases (AIDs). However, comprehensive clinical evidence establishing the association between specific LPO biomarkers and AIDs is lacking. To systematically evaluate the clinical evidence for elevated LPO in major AIDs through a meta-analysis, focusing on key biomarkers including malondialdehyde (MDA) and 8-isoprostaglandin F2α (8-isoPGF2α). We searched four databases for studies reporting serum, plasma, or urinary LPO levels in patients with AIDs and healthy controls. Standardized mean differences (SMDs) were pooled using a random-effects model. Across 175 studies (8227 patients; 6866 controls), serum/plasma MDA levels were significantly elevated in all ten investigated AIDs: Rheumatoid arthritis (RA) (SMD = 2.82), systemic sclerosis (SSc) (SMD = 2.08), graves' disease (GD) (SMD = 1.92), Behçet's disease (BD) (SMD = 1.90), Crohn's disease (CD) (SMD = 1.71), multiple sclerosis (MS) (SMD = 1.52), psoriasis (PsO) (SMD = 1.44), ulcerative colitis (UC) (SMD = 1.32), systemic lupus erythematosus (SLE) (SMD = 1.20) and type 1 diabetes (T1DM) (SMD = 1.12). Disease-specific elevations were found for serum/plasma 8-isoPGF2α and 4-hydroxynonenal in RA, urinary 8-isoPGF2α in SSc and T1DM, and serum/plasma oxidized low-density lipoprotein in T1DM. MDA was higher in active or severe subgroups, with significant between-subgroup differences in GD and PsO. This meta-analysis provides robust, large-scale clinical evidence that elevated lipid peroxidation is a common feature across diverse AIDs. These findings solidify the clinical relevance of ferroptosis, positioning LPO products as promising biomarkers and underscoring the therapeutic potential of targeting ferroptosis in autoimmune conditions.
Behçet's disease (BD) is characterized by relapsing mucocutaneous and major organ involvement. Although conventional immunosuppressants and CSs remain the mainstay of therapy, severe or refractory cases often require biologics. TNF-α inhibitors, particularly infliximab (IFX) and adalimumab (ADA), have become central to BD management. We compared the efficacy, safety, and drug retention of IFX and ADA in a real-world single-centre cohort. Eighty-seven BD patients receiving IFX (n = 45) or ADA (n = 42) as their first anti-TNF therapy between April 2020 and 2025 were retrospectively reviewed. Baseline demographics, organ involvement, laboratory parameters, treatment regimens, and outcomes were recorded. Except for a tendency of male predominance in the IFX group, baseline demographics were comparable. Vascular (51.1% vs 26.2%) and neurological (15.6% vs 2.4%) involvement were more frequent in the IFX group, while ocular disease predominated in the ADA group (45.2% vs 28.9%). Complete remission was achieved in 75.6% (IFX) and 78.6% (ADA) initially, increasing to 88.9% and 76.5%, respectively, at the last visit. Concomitant AZA use exceeded 60% in both groups, while pulse glucocorticoids, CYC, and anticoagulants were more common with IFX. Relapses occurred more often and earlier with IFX (37.8% vs 16.7%, median 8 vs 13 months). Drug retention and adverse event rates were comparable (IFX 80% vs ADA 85.7%; ∼16% adverse events). No severe events occurred. Both IFX and ADA were highly effective and well tolerated in severe or refractory BD. ADA provided durable control in mucocutaneous and ocular phenotypes, whereas IFX offered rapid remission in vascular and neurological disease. Phenotype-oriented and individualized treatment strategies may optimize anti-TNF use in BD.
A newsletter discute o potencial do baricitinibe em pacientes com uveíte associada à AIJ refratários a biológicos e destaca como a mudança para equações de função pulmonar neutras em relação à raça altera significativamente a classificação de gravidade na esclerose sistêmica. Além disso, aborda evidências recentes sobre a eficácia do adalimumabe na Síndrome de Behçet e os benefícios metabólicos e inflamatórios dos agonistas de GLP-1 na artrite reumatoide.
Infliximab (IFX) is an immunosuppressive drug widely used for the treatment of patients with Behçet's syndrome (BS) with severe or refractory organ involvements. The aim of this study was to evaluate IFX survival, clinical response and safety profile in a monocentric cohort of BS patients. Patients with BS treated with IFX intravenously across a 20-year period were retrospectively-prospectively examined. Total duration of therapy and drug retention until the end of follow-up were calculated, as well as the reasons of discontinuation, including adverse events. Clinical response, expressed as changes in BDCAF (Behçet's Disease Current Activity Form) indexacross the follow-up period, were evaluated and compared among patients. Sixty patients with BS were treated with IFX over a 20-year period. Overall drug retention was 45%, with survival rates of 78.3% at 1 year, 63.3% at 2 years, and 35% at 5 years (median duration 37 months, IQR 17-72). Most discontinuations occurred after 24 months and were mainly due to loss of efficacy (25%), de novo manifestations (21%), or allergic reactions (18%). Clinical activity improved markedly, with a mean BDCAF reduction of 4 points, ranging from -3.0 in mild to -5.7 in highly active disease. Continuers showed lower BDCAF scores at last follow-up and achieved higher remission and major response rates compared with discontinuers. Younger age and female sex were associated with higher discontinuation risk. Over the two decades, IFX indications shifted from major-organ involvement to predominantly refractory muco-cutaneous disease. IFX showed good safety profile and excellent clinical response in this real-world BS cohort, with a drug survival of 45% within a median treatment duration of 37 months.