RESUMEN
Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0-2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients.
Asunto(s)
Antirreumáticos , Hidroxicloroquina , Cumplimiento de la Medicación , Síndrome de Sjögren , Humanos , Hidroxicloroquina/sangre , Hidroxicloroquina/uso terapéutico , Femenino , Estudios Transversales , Persona de Mediana Edad , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/sangre , Masculino , Antirreumáticos/sangre , Antirreumáticos/uso terapéutico , Adulto , Anciano , Encuestas y CuestionariosRESUMEN
Yellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (â¼5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293;p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas.
RESUMEN
OBJECTIVE: Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). METHODS: Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. RESULTS: There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). CONCLUSIONS: We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.
Asunto(s)
Antirreumáticos , Lupus Eritematoso Sistémico , Nefritis Lúpica , Adulto , Antirreumáticos/uso terapéutico , Cromatografía Liquida , Humanos , Hidroxicloroquina/sangre , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológicoRESUMEN
OBJECTIVE: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). METHODS: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Age- and sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P <3), normal weight (3≤P≤85), overweight (85
97). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariate analyses were performed. RESULTS: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p <0.001), patient's/parent's global assessment of disease activity (PGA) (p=0.020), physician's global assessment of disease activity (PhGA) (p <0.001), erythrocyte sedimentation rate (ESR) (p=0.032) and overall higher JADAS-27 (p <0.001), compared to patients with normal weight, overweight and obesity. In the multivariate regression, underweight persisted significantly associated with higher disease activity, compared to normal weight (B=-9.430, p <0.001), overweight (B=-9.295, p=0.001) and obesity (B=-9.120, p=0.001), when adjusted for age, gender, country, ethnicity, JIA category and therapies used. The diagnosis of RF- (B=3.653, p=0.006) or RF+ polyarticular JIA (B=5.287, p=0.024), the absence of DMARD therapy (B=5.542, p <0.001) and the use of oral GC (B=4.984, p=0.002) were also associated with higher JADAS-27. CONCLUSION: We found an independent association between underweight and higher disease activity in patients with JIA. Further studies are needed to understand the underlying mechanisms of this association.
Asunto(s)
Artritis Juvenil , Artritis Juvenil/complicaciones , Artritis Juvenil/epidemiología , Índice de Masa Corporal , Brasil/epidemiología , Etnicidad , Femenino , Humanos , Masculino , Portugal/epidemiología , Índice de Severidad de la EnfermedadRESUMEN
Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn's disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-alpha) antagonistic agents, which is now available (infliximab, etanercept, and adalimumab). However, a portion of patients persists with active disease, infusion reactions, and relapses even during current biological therapy. One of the reasons for this is the associated immunogenicity to these drugs. The incentive for induction of antibodies against anti-TNF-alpha agent depends mainly on its constitution. Chimerical drugs have a higher capacity of inducing immunogenicity compared to completely human drugs. Among the three anti-TNF-alpha agents, this phenomenon has been studied mainly in patients using infliximab, especially in RA and CD. The prevalence of anti-infliximab antibodies in RA varies from 12% to 44% and seems to be inversely proportional to the level of seric infliximab and therapeutic response. The use of etanercept was associated to the development of anti-etanercept antibodies in 0% to 18% of patients, without apparent effect on effectiveness or adverse events. Studies with RA and CD patients show prevalence of anti-adalimumab antibodies from 1% to 87%. Immunosuppressive drug addiction can reduce the induction of anti-TNF-alpha antibodies.