RESUMEN
OBJECTIVES: To investigate genotype-phenotype correlation and gene-environment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients. METHODS: An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-environment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI). RESULTS: PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001]. Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-environment interaction was detected. CONCLUSION: These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA.
Asunto(s)
Artritis Reumatoide/genética , Ambiente , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Biomarcadores/sangre , Estudios de Cohortes , Terapia de Reemplazo de Estrógeno , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Fenotipo , Proteína Tirosina Fosfatasa no Receptora Tipo 22/metabolismo , Factor Reumatoide/sangre , Factores de RiesgoRESUMEN
OBJECTIVE: Rituximab has been shown to be effective in refractory rheumatoid arthritis (RA) in randomized controlled trials, allowing approval by health agencies. Our aim was to assess in routine care the effects of rituximab in patients with RA who had experienced an inadequate response to anti-tumor necrosis factor-alpha (TNF-alpha) agents or had a contraindication to these drugs. METHODS: An observational retrospective study was conducted. Rituximab (1000 mg intravenous infusion on Days 1 and 15) was administered with concomitant methotrexate therapy. Responses defined according to the European League Against Rheumatism (EULAR criteria) were assessed at Week 24. RESULTS: Fifty patients were included: 30 had inadequate response to anti-TNF-alpha and 20 had contraindication to anti-TNF-a drugs. EULAR response was observed in 82%, good response in 36% (including remission in 12%), moderate response in 46%, and no response in 18%. One infusion-related reaction and 2 pulmonary infections occurred. Eleven of the 50 patients (22%) experienced flare and received retreatment with rituximab at 6 months. Thirty additional patients had flare after 6 months and the median delay for retreatment among the 41 responders was 9 (range 6 24) months. No difference regarding efficacy or tolerance of rituximab was observed according to previous inadequate response or contraindication to anti-TNF. CONCLUSION: A single cycle of rituximab, in combination with continued methotrexate, provided significant improvement in disease activity at Week 24, with good tolerance, in patients with severe and active RA despite anti-TNF-alpha agents and/or with contraindication to these drugs, in this daily practice study.