ABSTRACT
Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient's response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.
ABSTRACT
OBJECTIVES: To describe the methodology, objectives, and initial data of the registry of young adult patients diagnosed with Juvenile Idiopathic Arthritis (JIA), JUVENSER. The main objective of the project is to know the sociodemographic and clinical characteristics, and disease activity of patients with JIA reaching the transition to adulthood. MATERIAL AND METHOD: Longitudinal, prospective, multicentre study, including patients between 16 and 25 years old, with a diagnosis of JIA in any of its categories. The main objective is to determine the characteristics and activity of JIA in the young adult. It includes sociodemographic variables, clinical variables, disease activity and joint damage rates, data on the use of health resources, and treatments used. The total duration of the project will be 3 years. A cohort of 534 young adult patients was obtained. CONCLUSIONS: The JUVENSER registry will constitute a cohort of young adults with JIA, which will allow the evaluation of the clinical characteristics and response to treatment of patients with disease onset in childhood, moving to adult clinics.
Subject(s)
Antirheumatic Agents , Arthritis, Juvenile , Humans , Young Adult , Adolescent , Adult , Arthritis, Juvenile/therapy , Arthritis, Juvenile/drug therapy , Antirheumatic Agents/therapeutic use , Prospective Studies , RegistriesABSTRACT
La dermatomiositis juvenil es el subtipo más frecuente del grupo de las miopatías idiopáticas inflamatorias en la edad pediátrica. Clínicamente se caracteriza por la presencia de debilidad muscular proximal y simétrica con afectación cutánea característica. El diagnóstico clásicamente se ha basado en los criterios de Bohan y Peter (1975). Sin embargo, en 2017, el International Myositis Assessment and Clinical Studies Group (IMACS) ha publicado unos criterios de clasificación de las miopatías idiopáticas inflamatorias donde es posible clasificar a un paciente sin necesidad de biopsia. La patogenia de la enfermedad es compleja y no del todo conocida. Están involucrados el sistema inmune innato y adaptativo, donde juega un papel muy importante el interferón, y donde existen agentes externos como infecciones o factores medioambientales que actuarían como desencadenantes en sujetos genéticamente predispuestos. El tratamiento ha de ser intensivo desde el inicio, con el objetivo de controlar la enfermedad cutánea y muscular de forma precoz, minimizar complicaciones como la calcinosis, más frecuente en niños que en adultos, y mejorar el pronóstico a largo plazo. Presentamos el caso de una niña prepúber en cuyo debut de la enfermedad solo presentaba dolor e impotencia funcional en pierna izquierda, con antecedente de traumatismo de baja energía, sin elevación de enzimas musculares, lesiones cutáneas ni una biopsia muscular típica (AU)
uvenile dermatomyositis is the most common idiopathic inflammatory myopathy subtype in the paediatric age group. Clinically, it is characterized by proximal and symmetrical muscle weakness with characteristic skin lesions. Traditionally, the diagnosis has been based on the Bohan and Peter criteria (1975). However, the International Myositis Assessment and Clinical Studies Group (IMACS) published new classification criteria in 2017 that allow classification of the disease without a biopsy. The pathogenesis of the disease is complex and has not been fully elucidated. It involves innate and adaptive immunity, with interferon playing a key role, and external agents like infections or environmental factors acting as triggers of the disease in genetically predisposed people.Treatment must be intensive from the beginning to achieve early control of cutaneous and muscular disease, reduce complications such as calcinosis, which is more frequent in children than in adults, and improve long-term outcomes.We present the case of a prepubertal girl who had onset with pain and left leg dysfunction and reported a history of low-energy trauma, without muscle enzyme elevation, skin lesions or a typical muscle biopsy. (AU)
Subject(s)
Humans , Female , Child , Dermatomyositis/diagnosis , Methylprednisolone/therapeutic use , Glucocorticoids/therapeutic use , Hydroxychloroquine/therapeutic use , Antirheumatic Agents/therapeutic use , Dermatomyositis/drug therapy , Treatment OutcomeABSTRACT
Graves' orbitopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves' Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.
ABSTRACT
No disponible
