RESUMEN
Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.
Asunto(s)
Adamantano/análogos & derivados , Artritis Reumatoide/tratamiento farmacológico , Niacinamida/análogos & derivados , Adamantano/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Quinasas Janus/antagonistas & inhibidores , Niacinamida/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.
RESUMEN
The CD40 pathway is involved in the development and pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) in the CD40 gene, rs1883832 and rs4810485, are associated with susceptibility to inflammatory and autoimmune diseases and are thought to alter CD40 expression at the mRNA and protein level. This study assessed for the first time the association of these SNPs with RA and CD40 mRNA levels in a western Mexican population. A total of 278 RA patients and 318 control subjects were included. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and CD40 mRNA expression was determined by real-time quantitative PCR. No significant differences in genotype and allele frequencies were identified between the RA patients and controls. When stratified by genotype, these SNPs were not found to be associated with the presence of autoantibodies or the clinical activity of the disease. CD40 mRNA levels were elevated 1.5-fold in RA patients compared to control subjects; however, no clear tendencies were observed following stratification by genotype. These results suggest that the CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression.
Asunto(s)
Artritis Reumatoide/genética , Antígenos CD40/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Adulto , Anciano , Artritis Reumatoide/patología , Antígenos CD40/biosíntesis , Femenino , Regulación de la Expresión Génica , Genotipo , Humanos , Masculino , México , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Mensajero/biosíntesis , ARN Mensajero/genéticaRESUMEN
A traditional infectious disease vaccine is a preparation of live attenuated, inactivated or killed pathogen that stimulates immunity. Vaccine immunologic adjuvants are compounds incorporated into vaccines to enhance immunogenicity. Adjuvants have recently been implicated in the new syndrome named ASIA autoimmune/inflammatory syndrome induced by adjuvants. The objective describes the frequencies of post-vaccination clinical syndrome induced by adjuvants. We performed a cross-sectional study; adverse event following immunization was defined as any untoward medical occurrence that follows immunization 54 days prior to the event. Data on vaccinations and other risk factors were obtained from daily epidemiologic surveillance. Descriptive statistics were done using means and standard deviation, and odds ratio adjusted for potential confounding variables was calculated with SPSS 17 software. Forty-three out of 120 patients with moderate or severe manifestations following immunization were hospitalized from 2008 to 2011. All patients fulfilled at least 2 major and 1 minor criteria suggested by Shoenfeld and Agmon-Levin for ASIA diagnosis. The most frequent clinical findings were pyrexia 68%, arthralgias 47%, cutaneous disorders 33%, muscle weakness 16% and myalgias 14%. Three patients had diagnosis of Guillain-Barre syndrome, one patient had Adult-Still's disease 3 days after vaccination. A total of 76% of the events occurred in the first 3 days post-vaccination. Two patients with previous autoimmune disease showed severe adverse reactions with the reactivation of their illness. Minor local reactions were present in 49% of patients. Vaccines containing adjuvants may be associated with an increased risk of autoimmune/inflammatory adverse events following immunization.
Asunto(s)
Adyuvantes Farmacéuticos/efectos adversos , Diabetes Mellitus Tipo 1/epidemiología , Vacunas/efectos adversos , Anomalías Múltiples/epidemiología , Adyuvantes Farmacéuticos/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artralgia/epidemiología , Autoinmunidad/efectos de los fármacos , Niño , Preescolar , Estudios Transversales , Femenino , Fiebre/epidemiología , Estudios de Seguimiento , Síndrome de Guillain-Barré/epidemiología , Humanos , Incidencia , Lactante , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Enfermedades de la Piel/epidemiología , Síndrome , Vacunación/efectos adversos , Vacunas/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVE: To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS: Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy. CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Inhibidores de la Ciclooxigenasa/efectos adversos , Diclofenaco/efectos adversos , Lactonas/efectos adversos , Misoprostol/efectos adversos , Osteoartritis/tratamiento farmacológico , Dolor Abdominal/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Diarrea/inducido químicamente , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/fisiopatología , Índice de Severidad de la Enfermedad , Sulfonas , Resultado del TratamientoRESUMEN
The increasing prevalence of complementary and alternative medicine usage by the general population and rheumatic patients worldwide is reviewed. The many potential concerns about this type of therapy are addressed, ranging from toxicity issues to changes in behavioral attitudes. Finally, the authors speculate on some major socioeconomic outcomes associated with these therapies.
Asunto(s)
Terapias Complementarias/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Enfermedades Reumáticas/terapia , Reumatología/tendencias , Salud Global , HumanosRESUMEN
OBJECTIVE: To investigate the prevalence of anticardiolipin antibodies (aCL) and isotype distribution and their clinical associations with the features of the antiphospholipid syndrome (APS) in 3 different ethnic groups of patients with systemic lupus erythematosus (SLE). METHODS: The study population consisted of 152 African-American, 136 Afro-Caribbean (Jamaican), and 163 Hispanic (Colombian) unselected patients with SLE. Serum samples were studied for the prevalence of aCL and isotype distribution. All aCL measurements were performed in the same laboratory by ELISA. RESULTS: Positive results for 1 of the 3 aCL isotypes were found in 42 African-Americans (28%), 28 Afro-Caribbeans (21%), and 43 Hispanics (26%). IgG aCL was the dominant isotype in Hispanic and African-American patients, while IgA was the dominant isotype in Afro-Caribbeans. Of note, IgA aCL was found in all Afro-Caribbean patients who were aCL positive, while only 3 patients in this group had IgG aCL and 2 had IgM aCL. Clinical features of the APS were found to correlate better in Hispanics than in African-Americans and Afro-Caribbean patients with aCL isotypes. CONCLUSION: Our data suggest the existence of ethnic differences in the prevalence and isotype distribution of aCL as well as in their clinical relevance in patients with SLE. Further studies of the role of genetic and/or environmental factors in the observed differences are required.
Asunto(s)
Anticuerpos Anticardiolipina/análisis , Isotipos de Inmunoglobulinas/análisis , Lupus Eritematoso Sistémico/etnología , Lupus Eritematoso Sistémico/inmunología , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/etnología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Niño , Preescolar , Colombia/etnología , Ensayo de Inmunoadsorción Enzimática , Etnicidad , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Jamaica/etnología , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Estados Unidos/etnologíaRESUMEN
In a study of 222 patients with vasculitis, we identified 11 who had an associated neoplasia. Seven had hematological neoplasia and 4 had solid malignant tumors. In 4 patients vasculitis gave the first evidence of the neoplasia or of its recurrence. Nine of our patients had cutaneous vasculitis. The other 2 had vasculitis involving the intestine and resulted in acute abdomens. These 2 patients needed prednisone treatment for the vasculitis. Neoplasia should be considered in patients with vasculitis without an apparent cause.