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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
BACKGROUND: Numerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn's disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia. METHODS: We conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy. RESULTS: Among the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group. CONCLUSIONS: This study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.
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Adalimumab , Enfermedad de Crohn , Infliximab , Inducción de Remisión , Ustekinumab , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Adalimumab/uso terapéutico , Infliximab/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Adulto , Ustekinumab/uso terapéutico , Resultado del Tratamiento , Fármacos Gastrointestinales/uso terapéutico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Hospitalización/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.
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Artritis Psoriásica , Artritis Reumatoide , Tuberculosis Latente , Espondilitis Anquilosante , Prueba de Tuberculina , Factor de Necrosis Tumoral alfa , Humanos , Estudios Retrospectivos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Espondilitis Anquilosante/tratamiento farmacológico , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Anciano , Estudios de Cohortes , Enfermedades Endémicas , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
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
INTRODUCTION: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF. METHODS AND ANALYSIS: The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle. ETHICS AND DISSEMINATION: Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA. TRIAL REGISTRATION NUMBER: NCT03445845 and EudraCT2017-004700-22.
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Antirreumáticos , Espondiloartritis Axial , Insuficiencia del Tratamiento , Humanos , Antirreumáticos/uso terapéutico , Espondiloartritis Axial/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Interleucina-17/antagonistas & inhibidores , Estudios Multicéntricos como Asunto , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
INTRODUCTION: This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA). METHODS: Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May 2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6 months from treatment switch. Fatigue and treatment adherence were measured ≥ 6 months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA. RESULTS: Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111). CONCLUSION: Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.
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Antirreumáticos , Artritis Reumatoide , Compuestos Heterocíclicos con 3 Anillos , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Estudios Transversales , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Anciano , Sustitución de Medicamentos/estadística & datos numéricos , Adulto , Índice de Severidad de la EnfermedadRESUMEN
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
In recent years Janus kinase inhibitors (JAKi) have joined tumor necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors (IL-17i) as approved disease modifying anti-rheumatic drugs (DMARD) for moderate to severe forms of axial spondyloarthritis (axSpA). Drug survival in axSpA patients has not been well studied in a real-world outpatient scenario since the approval of JAKi. We aimed to analyze the three drug classes based on modes of actions (MoA) for their persistence rates among German axSpA outpatients. A retrospective analysis of the RHADAR database for axSpA patients with a new initiation of TNFi, IL-17i, or JAKi treatment between January 2015 and October 2023 was conducted. Analyses included Kaplan-Meier curves and adjusted Cox regressions for drug discontinuation. 1222 new biological DMARD (TNFi [n = 954], IL-17i [n = 190]) or JAKi (n = 78) treatments were reported. The median drug survival was 31 months for TNFi, 25 for IL-17i, and 18 for JAKi. The corresponding 2-year drug survival rate was 79.6%, 72.6%, and 62.8% for TNFi, IL-17i, and JAKi, respectively. The probability for discontinuation for JAKi was significantly higher compared with TNFi (HR 1.91 [95% CI 1.22-2.99]) as well as for IL-17i compared with TNFi (HR 1.43 [95% CI 1.02-2.01]), possibly related to more frequent use of TNFis as first-line therapy. IL-17i and JAKi discontinuation probabilities were similar. Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA.
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Espondiloartritis Axial , Interleucina-17 , Inhibidores de las Cinasas Janus , Inhibidores del Factor de Necrosis Tumoral , Humanos , Estudios Retrospectivos , Interleucina-17/antagonistas & inhibidores , Masculino , Femenino , Adulto , Persona de Mediana Edad , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Espondiloartritis Axial/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Alemania , Factores de Tiempo , Resultado del TratamientoRESUMEN
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos , Células Madre Pluripotentes Inducidas , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Masculino , Adulto , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/citología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/deficiencia , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Femenino , Estallido Respiratorio , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/genética , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/metabolismo , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Interferón gamma/inmunología , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/farmacología , Homocigoto , Receptores Tipo I de Factores de Necrosis Tumoral/deficiencia , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Mycobacterium tuberculosis/inmunologíaRESUMEN
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 adversosRESUMEN
Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.
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Artritis Reumatoide , Interleucina-6 , Polimorfismo de Nucleótido Simple , Receptores Tipo II del Factor de Necrosis Tumoral , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Humanos , Artritis Reumatoide/genética , Artritis Reumatoide/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/genética , Interleucina-6/genética , Interleucina-6/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Anciano , Estudios de Casos y Controles , Antirreumáticos/uso terapéuticoAsunto(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
This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.
Asunto(s)
Abatacept , Antirreumáticos , Artritis Reumatoide , Interleucina-6 , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Masculino , Interleucina-6/antagonistas & inhibidores , Interleucina-6/metabolismo , Persona de Mediana Edad , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Antirreumáticos/farmacología , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Anciano , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Articulación de la Rodilla/efectos de los fármacos , Adulto , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/farmacología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
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.