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PURPOSE: To assess structural (optical coherence tomography, fundus autofluorescence) and functional (contrast sensitivity and visual field) test results which were used for detecting early retinal changes in patients using oral hydroxychloroquine. METHODS: Patients using oral hydroxychloroquine for at least one year were divided into two groups according to the duration of drug use. Groups 1 and 2 consisted of patients with drug use for more than 5 years and 1-5 years, respectively. The drug-using groups were compared with the control group. The mean retinal nerve fiber layer (RNFL), central macular thickness (CMT), ganglion cell-inner plexiform layer (GC-IPL), static 10-2 visual field, fundus autofluorescence (FAF) imaging, and contrast sensitivity tests were performed and statistically compared between groups. RESULTS: Median and temporal quadrant RNFL thicknesses were found to be statistically significantly lower in the drug groups. In the drug groups, the GC-IPL sectoral and mean thicknesses were found to be statistically lower in all quadrants. Central macular thickness was also found to be similar in all three groups. There was no significant difference between the groups in visual field parameters. Macular FAF images were significantly higher in the drug users, but there was no significant difference between the three groups in foveal FAF images. Contrast sensitivity measurements were significantly lower in the drug groups than in the control group at all spatial frequencies except 6 and 18 cycles/degree. CONCLUSIONS: The combined use of structural and functional tests in patients using hydroxychloroquine provides useful information in detecting early retinal changes.
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Antirreumáticos , Sensibilidad de Contraste , Diagnóstico Precoz , Angiografía con Fluoresceína , Hidroxicloroquina , Mácula Lútea , Enfermedades de la Retina , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Campos Visuales , Humanos , Hidroxicloroquina/efectos adversos , Tomografía de Coherencia Óptica/métodos , Femenino , Masculino , Campos Visuales/fisiología , Campos Visuales/efectos de los fármacos , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Mácula Lútea/efectos de los fármacos , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/efectos de los fármacos , Sensibilidad de Contraste/fisiología , Sensibilidad de Contraste/efectos de los fármacos , Angiografía con Fluoresceína/métodos , Adulto , Fibras Nerviosas/patología , Fibras Nerviosas/efectos de los fármacos , Agudeza Visual , Pruebas del Campo Visual/métodos , AncianoRESUMEN
Background: Safety recommendations for Janus kinase inhibitors (JAKi) issued by the European Medical Agency (EMA) in 2023 could potentially influence treatment patterns for rheumatoid arthritis (RA) drugs, but little is known about the impact of these recommendations in routine clinical care. Methods: We retrospectively analyzed the German RHADAR rheumatology database for adult patients with RA and documentation of a new therapy with a JAKi, tumor necrosis factor inhibitor (TNFi), or interleukin-6 receptor inhibitor (IL-6Ri). Data were grouped into half-yearly intervals from quarter (Q)2/2020 to Q3/2023. The period from Q4/2022 to Q1/2023 immediately followed the initial EMA endorsement of Pharmacovigilance Risk Assessment Committee (PRAC) recommendations and Q2/2023-Q3/2023 immediately followed the direct healthcare provider communication (DHPC) containing the new safety JAKi recommendations. Results: Between April 1, 2020 and September 23, 2023, 3008 newly initiated therapies for TNFi (1499 [49.8%]), JAKi (1126 [37.4%]), and IL-6Ri (383 [12.7%]) were documented by the treating physicians. JAKi were increasingly used in the first two half-year periods (from 29.7% of these therapies in Q2/2020-Q3/2020 to 46.7% in Q2/2021-Q3/2021; odds ratio [OR] 2.08; p<0.001). The proportion of initiated JAKi therapies decreased significantly after the PRAC recommendations (32.9%; OR vs peak 0.56; p=0.001) and the DHPC letter (26.1%; OR vs peak 0.40; p<0.001). JAKi were more likely to be used as >3rd-line therapy in later time periods. Conclusions: This exploratory study suggests that EMA safety recommendations for JAKi influenced treatment patterns of RA patients who received JAKi in Germany. Additional studies will be needed to confirm these findings.
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Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Estudios Retrospectivos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Anciano , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Farmacovigilancia , Adulto , Europa (Continente) , AlemaniaRESUMEN
OBJECTIVE: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). METHODS: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. RESULTS: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). CONCLUSION: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
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Antirreumáticos , Artritis Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Metotrexato , Calidad de Vida , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/sangre , Femenino , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , Adulto , Factores de Tiempo , Dimensión del Dolor , Biomarcadores/sangre , Anciano , Mediadores de Inflamación/sangreRESUMEN
OBJECTIVE: To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019. METHODS: A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded. RESULTS: A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief. CONCLUSIONS: This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature.
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Antirreumáticos , Leflunamida , Enfermedades del Sistema Nervioso Periférico , Enfermedades Reumáticas , Humanos , Leflunamida/efectos adversos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Prevalencia , Nueva Zelanda/epidemiología , Anciano , Adulto , Antirreumáticos/efectos adversos , Factores de Riesgo , Factores de Tiempo , Conducción Nerviosa/efectos de los fármacosRESUMEN
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
BACKGROUND: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. METHODS: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. DISCUSSION: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. TRIAL REGISTRATION: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538.
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Adalimumab , Ansiedad , Artritis Psoriásica , Compuestos Heterocíclicos con 3 Anillos , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/psicología , Adalimumab/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/diagnóstico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions. CASE REPORT: We report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient's emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab. CONCLUSIONS: Although tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder.
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Adalimumab , Antirreumáticos , Artritis Juvenil , Trastorno Bipolar , Humanos , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/complicaciones , Masculino , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Niño , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Manía/inducido químicamente , AdolescenteRESUMEN
BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.
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Abatacept , Antirreumáticos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Abatacept/uso terapéutico , Abatacept/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Anciano , Resultado del Tratamiento , Progresión de la Enfermedad , Factores de Tiempo , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Factores de Riesgo , Adulto , República de Corea , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) typically affect women of childbearing age. One of the challenges in treating these women during pregnancy is to manage the disease while minimizing or avoiding the use of disease-modifying antirheumatic drugs (DMARDs) that may increase the risk to the mother or fetus. Biologic therapy has transformed the management of these patients. This study aimed to evaluate the maternal-fetal safety and perinatal outcomes in pregnant women with IMID exposed to biologic DMARDs either preconceptionally or during pregnancy and compare them with women using conventional DMARDs and a group of healthy pregnant women. METHODS: We conducted a retrospective study with prospective follow-up of pregnant women with IMID at a single center. We analyzed baseline maternal demographic characteristics, diseases, DMARDs, and maternal-fetal outcomes. RESULTS: A cohort of 244 pregnancies was studied. One hundred twenty-eight patients met classificatory criteria for rheumatic and musculoskeletal diseases (RMD) or inflammatory bowel disease (IBD), and 116 pregnancies of healthy women were evaluated from the same study period. One hundred and one pregnancies in IMID patients (89.84 %) occurred under immunosuppressive treatment, 78.91 % of IMID pregnancies were under cDMARD (33.59 % exclusive cDMARD), 56.25 % under bDMARD, and 27.34 % under oral glucocorticoids. Anti-TNF was the most frequent (88.88 %) bDMARD and was used in 50.78 % of the IMIDs. There was at least one flare in 37.10 % of the IMID pregnancies, and 9.38 % experienced more than one. Among flares, 43.48 % happened in the first trimester, 34.78 % in the second trimester, and 19.57 % in the third. Flares were more frequent in the RMD patients compared with IBD (p = 0.041; OR 2.15, 95%CI: 1.03-4.52). Flare was associated with discontinuation of bDMARD before the eighth week of gestation (p = 0.016), but especially in the second (p = 0.042) and third trimester (p = 0.012). Maternal infections were an infrequent complication overall (7.66 %), although more frequent in patients with IMIDs (p = 0.004) but were not associated with cDMARD or bDMARD. IMID patients needed assisted reproductive techniques (ART) more often (p = 0.001, OR 2.83, 95%CI: 1.02-7.90). More cesarean sections were performed in gestations under treatment with bDMARD (p = 0.020) and especially in those under treatment with anti-TNF. Aneuploidies calculation risk and fetal malformations were not correlated with DMARDs (cDMARDs, bDMARDs, or its combination) nor with any of the DMARDs individually preconcepcionally or during gestation. Small for gestational age (SGA) newborns were higher in patients with IMIDs however, it was not associated with DMARD use. DISCUSSION: In general, patients with IMIDs who require treatment with bDMARDs have a more severe or refractory disease prior to gestation. In our cohort, we found a higher risk of flare among patients with bDMARDs, especially when those were suspended early. Among maternal outcomes, we found that IMID patients needed ART more often. This is probably, first of all, because of maternal age. Among fetal outcomes, there are no differences in congenital malformations in the IMIDs and healthy patients and were not correlated with DMARDs. CONCLUSION: The use of bDMARDs was effective in disease control and safe from a maternal-fetal point of view, with no increase in prematurity, SGA, malformations, or infections.
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Antirreumáticos , Inmunosupresores , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Productos Biológicos/efectos adversos , Productos Biológicos/uso terapéutico , Resultado del Embarazo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Inflamación/inmunología , Estudios Prospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/inmunología , Estudios de SeguimientoRESUMEN
OBJECTIVE: The purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy. METHODS: Relevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at P<0.05. RESULTS: The meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = -0.03, 95% CI [-0.21, -0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = -0.23, 95% CI [-0.37, -0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P<0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: -0.23, 95% CI: [-0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55). CONCLUSION: Biologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.
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Artritis Reumatoide , Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Enfermedades Cardiovasculares/etiología , Factores Biológicos/uso terapéutico , HDL-Colesterol/sangre , Factores de Riesgo , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversosRESUMEN
OBJECTIVES: This study aimed to evaluate the long-term safety and efficacy profiles of ozoralizumab in patients with rheumatoid arthritis (RA) from the OHZORA, NATSUZORA and HOSHIZORA trials. METHODS: This study conducted an integrated analysis of the three trials. Patients who completed the OHZORA trial with concomitant treatment of ozoralizumab and methotrexate (MTX) or the NATSUZORA trial without MTX were eligible to participate in the long-term extension HOSHIZORA trial. Safety assessment was performed in the safety analysis set, and the incidence rate per 100 person-year (PY) was calculated for a summary of adverse events (AEs) and AEs of special interests (AESIs). The efficacy was analysed in terms of disease activity index response rates and functional remission. RESULTS: The OHZORA and NATSUZORA trials enrolled 521 patients, of whom 401 patients entered the HOSHIZORA trial and 279 completed the long-term extension treatment with a mean treatment duration of 200 weeks and total exposure of 1419.34 PY in all enrolled patients. Of the patients, 96.9% demonstrated ≥1 AEs, which is mostly mild to moderate. One death was observed, but no conspicuous AEs emerged and no specific concerns in AESIs were found through the long-term administration. The efficacy assessment revealed the maintained American College of Rheumatology response rates of 20%, 50%, and 70% during the trials. CONCLUSION: This integrated analysis revealed no new safety concerns, and the efficacy was maintained in patients with RA under long-term ozoralizumab administration. TRIAL REGISTRATION NUMBER: jRCT2080223971, jRCT2080223973, NCT04077567.
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Anticuerpos Monoclonales Humanizados , Antirreumáticos , Artritis Reumatoide , Metotrexato , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Quimioterapia Combinada , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program. METHODS: This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model. RESULTS: A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only. CONCLUSIONS: Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.
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Artritis Reumatoide , Infecciones , Aprendizaje Automático , Piperidinas , Pirimidinas , Pirroles , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Infecciones/inducido químicamente , Infecciones/epidemiología , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Ensayos Clínicos como AsuntoAsunto(s)
Artritis Reumatoide , Herpes Zóster , Inhibidores de las Cinasas Janus , Humanos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Factores de RiesgoAsunto(s)
Arritmias Cardíacas , Enfermedades Autoinmunes , Cloroquina , Hidroxicloroquina , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/epidemiología , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Factores de Riesgo , Medición de Riesgo , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacosRESUMEN
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
OBJECTIVE: The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). METHODS: The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. RESULTS: The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections. CONCLUSION: Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.
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Antirreumáticos , Artritis Juvenil , Etanercept , Humanos , Etanercept/efectos adversos , Etanercept/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Niño , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Adolescente , Resultado del Tratamiento , PreescolarRESUMEN
Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation.
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Artritis Psoriásica , Certolizumab Pegol , Humanos , Certolizumab Pegol/efectos adversos , Certolizumab Pegol/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Masculino , Antirreumáticos/efectos adversos , Sarcoidosis Pulmonar/inducido químicamente , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
Importance: Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. Objective: To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. Design, Setting, and Participants: This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Exposures: Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Main Outcomes and Measures: Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. Results: The SLE cohort included 52â¯883 patients (mean [SD] age, 44.23 [16.09] years; 45â¯255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16â¯892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. Conclusions and Relevance: In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.
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Antirreumáticos , Enfermedades Cardiovasculares , Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/inducido químicamente , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Estudios de Cohortes , Francia/epidemiología , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Factores de Riesgo , AncianoRESUMEN
We present two patients who developed multiple lower limb stress fractures. Potential causes, such as osteoporosis, malignancies and disturbances in calcium metabolism were investigated. This led the physicians to consider whether methotrexate (MTX) exposure posed a risk of atypical fractures.The association between MTX and lower limb fractures has been described in at least 80 cases in the literature. Stress fractures associated with MTX treatment are atypical of osteoporosis and located in the lower extremities, most often the tibia. The limited data suggest that discontinuation of MTX may improve symptoms and chances of fracture healing, while antiresorptive or osteoanabolic therapies have not proven clinically efficient. It seems evident, however, that the benefits of MTX treatment in rheumatological disease clearly outweigh the risk of MTX osteopathy and related fractures.