RESUMO
OBJECTIVE: We aimed to evaluate the clinical features, disease course, and associated factors for outcome in severe/refractory BD patients receiving TNF-i treatment. MATERIAL AND METHODS: This retrospective study was conducted by reviewing medical records from a tertiary referral center in Van province in Eastern Turkey. Data were obtained from patients' charts followed up between June 2019 and June 2022. RESULTS: We included 469 BD patients (59.3% male) whose 80 patients (17%) received TNF-i treatment in the study. The mean ± standard deviation of the patient age was 36.7 ± 10.1 years and the median (IQR) disease duration was 12 (12) years. IFX and ADAwere initiated in 67.5% (n = 54) and 32.5% (n = 26) patients, respectively. Overall and first-line retention rates of TNF-i were 84.7% and 92.6% for IFX and 83.3% and 80.8% for ADA, respectively. IFX was discontinued in 9 patients which were in 2 patients due to allergic reaction and tuberculosis, 3 patients for inefficacy, one patient for heart failure, and one patient for orbital zona. Although no serious adverse event was observed with ADA, 5 patients switched to IFX due to inefficacy. Overall, 72 patients (90%) resumed TNF-i at the end of the study; TNF-i was discontinued in 3 patients (3.8%) due to severe adverse events and in 5 patients (6.2%) with prolonged remission. CONCLUSION: In our study, no case of death was observed in TNF-i receiving patients. Most patients achieved attack-free and CS-free disease and retained TNF-i treatment. TNF inhibitors appear to be safe and effective in patients with severe/refractory Behçet's disease.
Assuntos
Adalimumab , Síndrome de Behçet , Humanos , Síndrome de Behçet/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Turquia , Pessoa de Meia-Idade , Adalimumab/uso terapêutico , Adalimumab/efeitos adversos , Infliximab/uso terapêutico , Infliximab/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Etanercepte/uso terapêutico , Etanercepte/efeitos adversosRESUMO
OBJECTIVES: Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs. METHODS: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis. RESULTS: A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses. CONCLUSION: This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.
Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Etanercepte/uso terapêutico , Estudos Longitudinais , Estudos Prospectivos , Proteômica , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Antirreumáticos/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Resultado do TratamentoRESUMO
OBJECTIVE: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907].
Assuntos
Espondiloartrite Axial , Etanercepte , Imageamento por Ressonância Magnética , Radiografia , Articulação Sacroilíaca , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Masculino , Espondiloartrite Axial/diagnóstico por imagem , Espondiloartrite Axial/tratamento farmacológico , Etanercepte/uso terapêutico , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.
Assuntos
Adalimumab , Antirreumáticos , Medicamentos Biossimilares , Etanercepte , Sistema de Registros , Doenças Reumáticas , Humanos , Feminino , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/administração & dosagem , Masculino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Adalimumab/uso terapêutico , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Etanercepte/uso terapêutico , Etanercepte/administração & dosagem , Adulto , Idoso , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/mortalidade , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Resultado do Tratamento , Injeções Subcutâneas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Espanha/epidemiologiaRESUMO
BACKGROUND: Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures. OBJECTIVES: To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. METHODS: Data from patients in the UK and the Republic of Ireland registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥ 50â years at treatment initiation were classified into early-onset psoriasis (EOP) (presenting in patients ≤ 40â years of age) and late-onset psoriasis (LOP) (presenting in patients > 40â years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02- or HLA-C*06:02 + . Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates. RESULTS: Final analytical cohorts included 4250 patients in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02- (48%)]. There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02-, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42-0.75). CONCLUSIONS: HLA-C*06:02, but not age at psoriasis onset, is a predictive biomarker for biologic survival in patients with psoriasis. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage patients with psoriasis.
Assuntos
Produtos Biológicos , Psoríase , Humanos , Adulto , Estudos de Coortes , Ustekinumab/uso terapêutico , Antígenos HLA-C , Dermatologistas , Sistema de Registros , Fatores Biológicos/uso terapêutico , Adalimumab/uso terapêutico , Psoríase/tratamento farmacológico , Etanercepte/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. METHODS: In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. RESULTS: 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). CONCLUSIONS: Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.
Assuntos
Adalimumab , Artrite Juvenil , Etanercepte , Uveíte , Humanos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/diagnóstico , Feminino , Masculino , Criança , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/etiologia , Estudos Retrospectivos , Itália/epidemiologia , Adolescente , Pré-Escolar , Etanercepte/efeitos adversos , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Adalimumab/uso terapêutico , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Lactente , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Fatores de Risco , Recidiva , Fatores de Tempo , Resultado do Tratamento , Exacerbação dos Sintomas , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.
Assuntos
Diabetes Mellitus , Transplante das Ilhotas Pancreáticas , Humanos , Etanercepte/uso terapêutico , Autoenxertos , Transplante Autólogo , Insulina , Inflamação , Citocinas , DNA , Pancreatectomia , Resultado do TratamentoRESUMO
Cystic white matter injury is highly associated with severe neurodevelopmental disability and cerebral palsy in preterm infants, yet its pathogenesis remains poorly understood and there is no established treatment. In the present study, we tested the hypothesis that slowly evolving cystic white matter injury after hypoxia-ischaemia is mediated by programmed necrosis initiated by tumour necrosis factor. Tumour necrosis factor blockade was begun 3 days after hypoxia-ischaemia to target the tertiary phase of injury, when most secondary cell death is thought to be complete. Chronically instrumented preterm foetal sheep (0.7 gestation) received 25 min of hypoxia-ischaemia induced by complete umbilical cord occlusion or sham-umbilical cord occlusion (controls, n = 10), followed by intracerebroventricular infusion of the soluble TNF inhibitor, Etanercept, at 3, 8 and 13 days after umbilical cord occlusion (n = 9) or vehicle (n = 9). Foetal brains were processed for histology at 21 days after umbilical cord occlusion. Umbilical cord occlusion with vehicle was associated with a spectrum of macroscopic white matter degeneration, including white matter atrophy, ventriculomegaly and overt temporal lobe cystic white matter injury. Oligodendrocyte maturational arrest and impaired labelling of myelin proteins, characteristic of diffuse white matter injury, was observed in the parietal lobe and surrounding the cystic lesions in the temporal lobe. Etanercept markedly attenuated cystic white matter injury on the side of the intracerebroventricular infusion, with partial contralateral protection. Further, Etanercept improved oligodendrocyte maturation and labelling of myelin proteins in the temporal and parietal lobes. The present study shows that cystic white matter injury reflects late-onset tertiary cell death mediated by delayed neuroinflammation through the tumour necrosis factor pathway. Delayed tumour necrosis factor blockade markedly attenuated cystic white matter injury and restored oligodendrocyte maturation and deficits in myelin protein expression. These data suggest that delayed tumour necrosis factor blockade may represent a viable therapeutic strategy to reduce the risk of cystic and diffuse white matter injury and potentially cerebral palsy after preterm birth, with a surprisingly wide therapeutic window.
Assuntos
Lesões Encefálicas , Paralisia Cerebral , Hipóxia-Isquemia Encefálica , Nascimento Prematuro , Substância Branca , Recém-Nascido , Humanos , Feminino , Ovinos , Animais , Substância Branca/patologia , Asfixia/complicações , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Etanercepte/metabolismo , Recém-Nascido Prematuro , Hipóxia-Isquemia Encefálica/patologia , Lesões Encefálicas/patologia , Fatores de Necrose Tumoral/metabolismoRESUMO
Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.
Assuntos
Anticorpos Monoclonais Humanizados , Artrite Psoriásica , Colite , Etanercepte , Interleucina-17 , Humanos , Feminino , Etanercepte/uso terapêutico , Etanercepte/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Pessoa de Meia-Idade , Interleucina-17/antagonistas & inibidores , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. OBJECTIVES: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. The aim of this study was to systematically evaluate the efficacy and safety of secukinumab for the treatment of moderate and severe plaque psoriasis and provide an evidence-based reference for clinical practice. METHODS: PubMed, Google Scholar, Cochrane Library, and Clinical Trials databases were searched. Pivotal phase III clinical trials were analysed. RevMan was used for the statistical analysis of the data. RESULTS: Seven pivotal phase III clinical trials were analysed. All trials evaluated secukinumab in moderate-to-severe plaque psoriasis and had two common primary end points: the proportion of respondents to the Psoriasis Area and Severity Index (PASI) and the proportion of respondents to the Investigator's Global Assessment (IGA). The total response ratios of PASI and IGA respondents in the secukinumab group were 82.8 and 71.3%, respectively, compared to placebo. Secukinumab was superior to etanercept, with risk ratios of 1.7 and 2.1, respectively. Secukinumab was generally well tolerated during the 1-year trial period. However, adverse events also occurred. CONCLUSION: Secukinumab was found to be more effective than etanercept and had an acceptable safety profile. Since psoriasis is an autoimmune disease that requires lifelong treatment, attention should be paid to its adverse effects.
Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Psoríase , Humanos , Anticorpos Monoclonais/efeitos adversos , Etanercepte/uso terapêutico , Interleucina-17 , Imunoglobulina A/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Método Duplo-Cego , Ensaios Clínicos Fase III como AssuntoRESUMO
In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague-Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)-α and interleukin (IL)-1ß, using an enzyme-linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti-IL-1ß and anti-TNF-α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF-α and IL-1ß. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.
Assuntos
Antirreumáticos , Artrite Reumatoide , Oxigenoterapia Hiperbárica , Interleucina-1beta , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa , Animais , Oxigenoterapia Hiperbárica/métodos , Masculino , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Artrite Reumatoide/terapia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Ratos , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Etanercepte/uso terapêutico , Etanercepte/farmacologia , Artrite Experimental/terapia , Artrite Experimental/patologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Leflunomida/uso terapêutico , Leflunomida/farmacologiaRESUMO
BACKGROUND: Psoriasis is a chronic skin condition, for which the approval of several biologics has made a dramatic impact. Despite their initial treatment effectiveness, the challenge lies in understanding the long-term responses, as they may diminish over time. Limitations of drug survival analysis warrant the application of additional outcomes to fully capture the performance of a biologic. OBJECTIVES: To provide a broader perspective on the global landscape of biologic agents' persistence in positive clinical response by comparing innovative therapies over a 5-year period through a systematic review and network meta-analysis. METHODS: We comprehensively identified studies in PubMed, Embase, Scopus and ClinicalTrials.gov. We defined two outcomes: (i) 'persistence at optimal response' (POR) or 'clinical remission', and (ii) 'persistence at suboptimal response' (PSR) or 'low disease activity'. Outcomes were measured as the proportions of patients with continuous exposure to a biologic who achieved ≥ 90% or 100% improvement in Psoriasis Area and Severity Index at the end of the predefined 5-year follow-up period. RESULTS: Eleven publications, comprising 18 randomized controlled trials and 11 202 patients, met the inclusion criteria and were included in the network meta-analysis. In the ranking analysis, guselkumab exhibited the highest cumulative probability of POR (0.84), followed by ixekizumab (0.82) and risankizumab (0.76). Conversely, etanercept (0.42), brodalumab (0.36), apremilast (0.25) and placebo (0.026) showed the lowest cumulative probabilities of POR. For PSR, guselkumab (0.86), ixekizumab (0.75) and risankizumab (0.71) also ranked highest, while brodalumab (0.42), secukinumab (0.23), etanercept (0.19) and placebo (0.019) presented the lowest PSR probabilities. CONCLUSIONS: The highest rates of persistence with clear or almost clear skin can be expected with guselkumab, ixekizumab and risankizumab compared with other biologics. The proposed proxy definitions of long-term persistence (POR and PSR) are reliable measures of patients being successfully treated that warrant further exploration and validation.
Assuntos
Produtos Biológicos , Fármacos Dermatológicos , Psoríase , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Etanercepte/uso terapêutico , Metanálise em Rede , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004-2020. Kaplan-Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation. Long-term disease activity trajectories were identified by latent class growth models using DAS28-ESR or ASDAS-CRP as outcome for RA and AxSpA respectively. We assessed 711 patients (450 RA, 178 AxSpA and 83 PerSpA) with a median (IQR) follow-up of 12 (5-32) months. At 5 years, 22%, 30% and 21% of RA, AxSpA and PerSpA patients, respectively, remained on therapy. Etanercept discontinuation was independent of the diagnosis and was predicted by gender and obesity in both RA and SpA groups. Four disease activity (DA) trajectories were identified from 6th month of treatment in both RA and AxSpA. RA patients in remission-low DA groups (33.7%) were younger, had shorter disease duration, fewer comorbidities and lower baseline disease activity compared to moderate (40.6%) & high DA (25.7%) groups. In AxSpA 74% were in inactive-low DA and they were more often males, non-obese and had lower number of comorbidities compared to higher ASDAS-CRP trajectories. In RA and AxSpA patients, disease activity trajectories revealed heterogeneity of TNFi treatment responses and prognosis. Male gender, lower baseline disease activity and fewer comorbidities, characterize a favourable outcome in terms of disease burden accrual and TNFi survival.
Assuntos
Antirreumáticos , Artrite Reumatoide , Espondiloartrite Axial , Espondilartrite , Humanos , Masculino , Etanercepte/uso terapêutico , Antirreumáticos/uso terapêutico , Estudos Prospectivos , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Fator de Necrose Tumoral alfaRESUMO
Vitamin D plays an important role in psoriasis, but its involvement in pathogenesis remains unclear. This study aimed to evaluate vitamin D receptor (VDR) expression on peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and healthy controls and to study the effects of the Etanercept treatment on VDR expression on PBMCs in patients with psoriasis. Twenty patients with moderate to severe psoriasis received treatment with Etanercept for 24 weeks. The age- and sex-matched controls did not receive any intervention. VDR expression on CD3+ lymphocytes and CD14+ monocytes, and serum levels of total and free 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) were analyzed at baseline, after 10-12 weeks, and after 24 weeks in both groups. VDR expression was analyzed using flow cytometry. We observed higher expression of the VDR on CD14+ monocytes in psoriasis patients compared to healthy controls at baseline. This difference was no longer significant after 24 weeks of the Etanercept treatment. The patients with psoriasis improved clinically. However, VDR expression was unaltered during the Etanercept treatment, and there was no correlation between VDR expression and disease severity.
Assuntos
Etanercepte , Leucócitos Mononucleares , Psoríase , Receptores de Calcitriol , Vitamina D , Humanos , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/genética , Masculino , Feminino , Leucócitos Mononucleares/metabolismo , Adulto , Pessoa de Meia-Idade , Etanercepte/uso terapêutico , Etanercepte/farmacologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Monócitos/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Estudos de Casos e ControlesRESUMO
A rare neuroendocrine skin cancer called Merkel cell carcinoma (MCC) primarily affects elderly people. The objective of this study is to comprehensively review the impact of immunosuppressive medications, particularly TNF inhibitors, on the emergence of MCC. METHODS: PubMed, Web of Science, Science Direct, and Cochrane Library were searched. Study articles were screened by title and abstract at Rayyan Qatar Computing Research Institute, then a full-text assessment was implemented. RESULTS: A total of eight case reports with 9 patients were included. Of the total population, seven were women and only two were men. Their age ranged from 31 to 73 years. More than half the population (5 cases) were being treated for rheumatoid arthritis. All received TNF inhibitors that were associated with the induction of MCC. CONCLUSION: We found that it is essential for physicians to explain potential cancer risks to patients before starting long-term immunosuppressive therapy and to conduct routine checks for MCC and other side effects. TNF inhibitors (infliximab, adalimumab, etanercept, and golimumab) were all associated with MCC development. Women constituted the majority of cases and most were elderly.
Assuntos
Carcinoma de Célula de Merkel , Etanercepte , Neoplasias Cutâneas , Inibidores do Fator de Necrose Tumoral , Humanos , Carcinoma de Célula de Merkel/induzido quimicamente , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Etanercepte/uso terapêutico , Etanercepte/efeitos adversos , Idoso , Feminino , Masculino , Infliximab/uso terapêutico , Infliximab/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Adalimumab/uso terapêutico , Adalimumab/efeitos adversos , Adulto , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.
Assuntos
Artrite Juvenil , Fibrose Endomiocárdica , Etanercepte , Humanos , Feminino , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/complicações , Fibrose Endomiocárdica/tratamento farmacológico , Fibrose Endomiocárdica/etiologia , Adulto Jovem , Etanercepte/uso terapêutico , Etanercepte/efeitos adversos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico , EcocardiografiaRESUMO
OBJECTIVES: To assess the usefulness and onset of nocebo effects after switching from the original etanercept (ETN) to a biosimilar (BS) in routine clinical practice at rheumatology clinics in Japan (13 sites). METHODS: A total of 165 patients (87.0% women, age = 57.88 ± 15.07 years, and disease duration = 10.32 ± 7.71 years), whose low disease activity was maintained with the original ETN for ≥12 weeks, and who agreed to switch treatment to its BS, were included. The end-points were disease activity score 28 (DAS28)-C-reactive protein and DAS28-erythrocyte sedimentation rate. RESULTS: No significant difference was observed between the changes in DAS28-C-reactive protein and DAS28-erythrocyte sedimentation rate >12 weeks before switching and >12 weeks after switching (P = 0.132 and 0.334, respectively). The treatment continuation rate during the 52 weeks after switching to BS was 97.3%. During this period, BS was discontinued in only four patients, and no nocebo effects were suspected in these four patients. CONCLUSION: Switching from ETN to BS was effective even in routine clinical practice at rheumatology clinics in Japan, and no nocebo effects were observed. Sufficient explanations to patients by rheumatologists and the additional payment for drug costs between patients at hospital visits effectively improved the continuation rate without any nocebo effect.
Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Etanercepte/uso terapêutico , Antirreumáticos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Efeito Nocebo , Japão , Proteína C-Reativa , Resultado do Tratamento , Artrite Reumatoide/tratamento farmacológicoRESUMO
OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.
Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Etanercepte , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Etanercepte/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Idoso , Resultado do Tratamento , Japão , Estudos de Coortes , AdultoRESUMO
OBJECTIVE: We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). METHODS: We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (<65, ≥65 and <75, and ≥75 years). RESULTS: Of 5506 patients, 2265 (41.1%) were <65 years, 1709 (31.0%) were 65-74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24-4.61); adalimumab, 1.90 (0.75-4.83); golimumab, 1.21 (0.66-2.23); and abatacept, 0.89 (0.49-1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11-0.85). CONCLUSION: In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.
Assuntos
Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Adulto , Idoso , Humanos , Antirreumáticos/efeitos adversos , Etanercepte/uso terapêutico , Japão/epidemiologia , Estudos Retrospectivos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Abatacepte/uso terapêutico , Produtos Biológicos/efeitos adversosRESUMO
This case report describes an uncommon overlap syndrome between ankylosing spondylitis (AS) and amyotrophic lateral sclerosis (ALS). Initially, the patient was diagnosed with AS, for which he received various specific treatments, including TNF-α inhibitors. After five years of treatment with TNF-α inhibitor etanercept, the patient was referred for a full neurological assessment after he reported balance disturbances, postural instability, muscle weakness, and other neurological symptoms that indicated the presence of a neurological disorder. After a thorough investigation, the patient was diagnosed with ALS. This case report aims to contribute to the limited literature by providing a detailed case study regarding the crosstalk between AS and ALS while also exploring the potential underlying mechanisms and the possible link between TNF-α inhibitors therapy and ALS.