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Anticuerpos Anticitoplasma de Neutrófilos , Anticuerpos Monoclonales , Glomerulonefritis por IGA , Humanos , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Resultado del Tratamiento , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Masculino , Biomarcadores/sangre , Biopsia , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Femenino , Persona de Mediana EdadRESUMEN
A previously healthy man developed pulmonary symptoms 2 weeks after starting treatment with a tumour necrosis factor (TNF) inhibitor. A negative interferon-gamma release assay (IGRA) test was obtained prior to TNF inhibitor exposure, without consideration of the fact that the patient was already immunosuppressed and had a previous positive IGRA test 17 months earlier. The patient was treated for pneumonia twice but did not achieve remission. His physical health progressively deteriorated over the following months. Malignancy was suspected but not found. Eight months after the onset of symptoms, Mycobacterium tuberculosis was found in samples from mediastinal lymph nodes, and the patient was diagnosed with multidrug-resistant tuberculosis (MDR-TB).This case illustrates the diagnostic challenge of TB, the need to raise awareness of the increased risk of TB in patients treated with TNF inhibitors and the need to increase knowledge regarding the effect of immunosuppressive agents on IGRA tests.
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Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Mycobacterium tuberculosis/aislamiento & purificación , Ensayos de Liberación de Interferón gamma , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Diagnóstico Erróneo , Antituberculosos/uso terapéutico , Persona de Mediana Edad , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Huésped InmunocomprometidoRESUMEN
Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.
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Abatacept , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/mortalidad , Artritis Reumatoide/complicaciones , Abatacept/uso terapéutico , Anciano , Adulto , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Hospitalización/estadística & datos numéricosRESUMEN
Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.
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Corticoesteroides , Quimioterapia Combinada , Inhibidores de Puntos de Control Inmunológico , Síndrome de Stevens-Johnson , Inhibidores del Factor de Necrosis Tumoral , Humanos , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/mortalidad , Síndrome de Stevens-Johnson/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Etanercept/efectos adversos , Etanercept/uso terapéutico , Resultado del Tratamiento , Infliximab/uso terapéutico , Infliximab/efectos adversosAsunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Metotrexato , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Metotrexato/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Antirreumáticos/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Reumatólogos , Encuestas y Cuestionarios , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
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.
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Carcinoma de Células de Merkel , Etanercept , Neoplasias Cutáneas , Inhibidores del Factor de Necrosis Tumoral , Humanos , Carcinoma de Células de Merkel/inducido químicamente , Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Etanercept/uso terapéutico , Etanercept/efectos adversos , Anciano , Femenino , Masculino , Infliximab/uso terapéutico , Infliximab/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Adulto , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
TNF inhibitors (TNFi) have revolutionized the therapeutic management of various chronic immune-mediated inflammatory diseases. Despite their known benefits, these therapies are related to paradoxical adverse effects (PAEs), including paradoxical psoriasis (PP). Although the underlying mechanism remains somewhat unclear, some theories suggest that genetic factors, particularly certain single-nucleotide polymorphisms (SNPs), may play an important role. The present review aimed to research and analyze recent findings regarding the pathomechanisms involved in the appearance of PP and the association between various genetic factors and PP in individuals treated with TNFi. We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.
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Polimorfismo de Nucleótido Simple , Psoriasis , Inhibidores del Factor de Necrosis Tumoral , Humanos , Psoriasis/genética , Psoriasis/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Predisposición Genética a la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Anticuerpos Antiproteína Citrulinada , Artritis Reumatoide , Humanos , Artritis Reumatoide/inmunología , Anticuerpos Antiproteína Citrulinada/sangre , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , FemeninoRESUMEN
Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.
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Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Productos Biológicos , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Femenino , Masculino , Persona de Mediana Edad , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Adulto , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/tratamiento farmacológico , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Interleucina-23/inmunología , Interleucina-23/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Prevalencia , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Índice de Severidad de la Enfermedad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
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.
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Adalimumab , Antirreumáticos , Biosimilares Farmacéuticos , Etanercept , Sistema de Registros , Enfermedades Reumáticas , Humanos , Femenino , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Adalimumab/uso terapéutico , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Etanercept/uso terapéutico , Etanercept/administración & dosificación , Adulto , Anciano , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/mortalidad , Estudios Prospectivos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Resultado del Tratamiento , Inyecciones Subcutáneas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , España/epidemiologíaRESUMEN
BACKGROUND: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA. METHODS: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002-2010, 2011-2019) to account for secular trends. RESULTS: Using phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29-0.40) in the cohort overall, and in the two time periods separately. CONCLUSION: In this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed.
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Espondiloartritis Axial , Enfermedades Cardiovasculares , Inhibidores del Factor de Necrosis Tumoral , Humanos , Masculino , Persona de Mediana Edad , Femenino , Enfermedades Cardiovasculares/epidemiología , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Incidencia , Anciano , Espondiloartritis Axial/epidemiología , Espondiloartritis Axial/diagnóstico por imagen , Estados Unidos/epidemiologíaRESUMEN
Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.
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Sistema de Registros , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Edad de Inicio , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND/OBJECTIVE: To assess safety/efficacy of tofacitinib and tumor necrosis factor inhibitors (TNFi) in patients from Latin America (LATAM) in ORAL Surveillance. METHODS: In ORAL Surveillance, 4362 patients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily or TNFi. This post hoc analysis stratified patients by geographical location (LATAM, n = 1202; non-LATAM, n = 3160). Incidence rates (IRs; patients with first event/100 patient-years) and hazard ratios for adverse events of special interest were reported. Efficacy outcomes included Clinical Disease Activity Index and American College of Rheumatology 20/50/70 responses. RESULTS: Risk factors associated with cardiovascular disease and malignancies were less prevalent in the LATAM cohort compared with the non-LATAM cohort. IRs for patients receiving tofacitinib (combined doses) versus TNFi were 0.54 versus 0.28 (LATAM) and 1.14 versus 0.92 (non-LATAM) for major adverse cardiovascular events; 0.58 versus 0.27 (LATAM) and 1.33 versus 0.95 (non-LATAM) for malignancies excluding nonmelanoma skin cancer; and 0.69 versus 0.35 (LATAM) and 0.63 versus 0.33 (non-LATAM) for all-cause death. IRs for nonmelanoma skin cancer and venous thromboembolism were also numerically higher with tofacitinib versus TNFi and in the non-LATAM cohort versus LATAM. Efficacy was similar across treatment groups within each cohort. CONCLUSIONS: Adverse events of special interest were generally less frequent in LATAM versus non-LATAM patients, reflecting differences in baseline characteristics, and higher with tofacitinib versus TNFi in both cohorts, consistent with the overall findings of ORAL Surveillance. Our findings emphasize the importance of assessing individual risk factors to guide benefit/risk assessment and treatment decisions. CLINICAL TRIAL REGISTRATION NUMBER: NCT02092467.
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Artritis Reumatoide , Enfermedades Cardiovasculares , Neoplasias , Piperidinas , Pirimidinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Incidencia , América Latina/epidemiología , Neoplasias/epidemiología , Neoplasias/tratamiento farmacológico , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Pirroles/efectos adversos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/administración & dosificaciónRESUMEN
OBJECTIVE: To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. METHODS: Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression. RESULTS: A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. CONCLUSION: Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
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Antirreumáticos , Artritis Reumatoide , Azetidinas , Purinas , Pirazoles , Sulfonamidas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Medición de Resultados Informados por el Paciente , Purinas/administración & dosificación , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Insuficiencia del Tratamiento , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/efectos adversosAsunto(s)
Adalimumab , Espondiloartritis Axial , Biosimilares Farmacéuticos , Humanos , Adalimumab/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Estudios Retrospectivos , China/epidemiología , Femenino , Masculino , Resultado del Tratamiento , Adulto , Espondiloartritis Axial/diagnóstico , Espondiloartritis Axial/inmunología , Espondiloartritis Axial/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
OBJECTIVES: Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM. METHODS: This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events. RESULTS: In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127-5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170-0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041-6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039-8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539-11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications. CONCLUSIONS: TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.
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Aborto Habitual , Resultado del Embarazo , Factor de Necrosis Tumoral alfa , Humanos , Femenino , Embarazo , Aborto Habitual/etiología , Aborto Habitual/tratamiento farmacológico , Adulto , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Estudios Retrospectivos , China , Nacimiento Vivo , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
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.
Asunto(s)
Adalimumab , Síndrome de Behçet , Humanos , Síndrome de Behçet/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Adulto , Turquía , Persona de Mediana Edad , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Infliximab/uso terapéutico , Infliximab/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Etanercept/uso terapéutico , Etanercept/efectos adversosRESUMEN
BACKGROUND: Although the clinical importance of preeclampsia is widely recognized, few treatment options are available for prevention. TNF-α inhibitors have been hypothesized to potentially prevent the disease. We aimed to examine whether exposure to TNF-α inhibitors during pregnancy reduces the risk of preeclampsia. METHODS: We conducted a population-based pregnancy cohort study using nationwide samples of publicly (Medicaid data, 2000-2018) and commercially (MarketScan Research Database, 2003-2020) insured pregnant women linked to their liveborn infants. Exposure was ascertained based on a filled prescription or administration code for TNF-α inhibitors during the first and second trimester of pregnancy. The outcomes included early-onset preeclampsia, late-onset preeclampsia, and small-for-gestational age. For baseline confounding adjustment, we leveraged propensity score overlap weights to estimate risk ratios (RR). RESULTS: Among 4â315â658 pregnancies in the Medicaid and the MarketScan cohort, 2736 (0.063%) were exposed to TNF-α inhibitors during the first trimester and 1712 (0.040%) during the second trimester. After adjustment, the risk of early-onset preeclampsia was not decreased among mothers exposed during the first trimester compared with unexposed women with treatment indications [RR pooled : 1.25, 95% confidence interval (CI) 0.93-1.67]. Similarly, the risk of late-onset preeclampsia was not decreased among mothers exposed during the second trimester compared with unexposed women (RR pooled : 0.99, 95% CI 0.81-1.22). CONCLUSION: Contrary to the hypothesis, exposure to TNF-α inhibitors during pregnancy did not appear to be associated with a reduced risk of early-onset or late-onset preeclampsia. These findings do not support consideration of the use of TNF-α inhibitors for the prevention of preeclampsia.
Asunto(s)
Preeclampsia , Factor de Necrosis Tumoral alfa , Humanos , Embarazo , Femenino , Preeclampsia/epidemiología , Preeclampsia/prevención & control , Adulto , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Estudios de Cohortes , Adulto Joven , Estados Unidos/epidemiología , Segundo Trimestre del Embarazo , Factores de Riesgo , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Primer Trimestre del EmbarazoRESUMEN
OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.