Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. / Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018.

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Factors predictive of high disease activity early in the course of SLE in patients from a Latin-American cohort.

AIMS: To determine the factors predictive of disease activity early in the course of SLE (baseline visit). METHODS: Patients from GLADEL, a multi-national, multi-ethnic, Latin-American lupus cohort were included. Disease activity was evaluated at baseline with the SLEDAI score. Demographic characteristics (age at diagnosis, gender, ethnicity, marital status, educational level, medical coverage and socioeconomic status) were assessed. Disease duration was defined as the time between the fourth ACR criterion and baseline. Time to criteria accrual was defined as the interval between the first and fourth ACR criterion. Use of glucocorticoids was recorded as the highest dose received before the baseline visit. Antimalarials and immunosuppressive drugs were recorded as use or not use. Univariable and multivariable analysis were performed. Model selection was based on backward elimination. RESULTS: One thousand two hundred sixty-eight patients were included; 1136 (89.6%) of them were female. Mean age at diagnosis was 29.2 (SD: 12.3) years. Five hundred sixty-five (44.6%) were Mestizo, 539 (42.5%) were Caucasians and 164 (12.9%) were African-Latin-Americans. The mean SLEDAI at baseline was 10.9 (SD: 8.4). Longer time between first and fourth ACR criterion, medical coverage, a dose of prednisone between 15 and 60mg/d, and the use of antimalarials were factors protective of disease activity, while Mestizo and African-Latin-American ethnicities were predictive factors. CONCLUSIONS: Mestizo and African-Latin-American ethnicities were predictive whereas antimalarial use, medical coverage, and longer time to criteria accrual were protective of higher disease activity early in the disease course.

A randomized, double-blind, multicenter, controlled clinical trial of cyclosporine plus chloroquine vs. cyclosporine plus placebo in early-onset rheumatoid arthritis.

BACKGROUND: Our objective was to assess the efficacy and safety of cyclosporine-A (CsA) plus chloroquine (Clq) in early-onset rheumatoid arthritis (RA) compared to CsA plus placebo. METHODS: We conducted a prospective, 12-month follow-up, multicenter, double-blind, placebo-controlled study of CsA (2.5-5 mg/kg/day[d]) plus Clq (150 mg/d) vs. CsA plus placebo in active RA of <2 years of evolution. RESULTS: A total of 149 patients were included; 111 patients (74.4%) completed the 12-month follow-up period. Evaluation at 6 and 12 months showed improvement for all clinical disease parameters. In both groups there was a decrease in tender joint count, swollen joint count, pain, assessment of efficacy by both investigator and patient, functional assessment, and morning stiffness, all differences statistically significant. With an intention-to-treat analysis, there was 64% in the CsA plus Clq group (CsA/Clq) and 63% in the CsA plus placebo group (CsA/Plac) at 12 months in the American College of Rheumatology (ACR)-20 criteria of improvement. Response rate for ACR-50 was 48 and 47%, and for ACR-70 it was 29% in both groups; the difference was not statistically significant between study groups. Gastrointestinal complaints were common in both groups. Four patients in CsA/Clq group and five patients in CsA/placebo group increased creatinine levels; two patients in each group discontinued treatment due to this reason. CONCLUSIONS: There was no advantage to adding chloroquine to cyclosporine in patients with RA.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Longitudinal study of antinuclear and anticardiolipin antibodies in pregnant women with systemic lupus erythematosus and antiphospholipid syndrome.

The objective of this study was to perform a longitudinal follow-up of antinuclear antibodies (ANAs) and anticardiolipin antibodies titers (aCL) throughout pregnancy in a group of patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients during their therapy for the prevention of fetal loss and to examine their relationship with pregnancy outcome. Thirty patients and 15 controls were followed in the study. Fifteen patients had SLE (group I) and 15 had APS (group II, of which seven patients had primary APS and eight had APS secondary to SLE). All patients were receiving therapy for the prevention of fetal loss with prednisone and aspirin as part of an ongoing clinical trial in lupus pregnancy. If there was a history of previous thrombosis, heparin was added. Blood samples were taken at the 1st, 2nd, and 3rd trimesters (T) of pregnancy in order to assess the presence of IgG and IgM aCL antibodies (ELISA), anti-dsDNA ( C. luciliae) ANAs (HEp-2 cells), and immunospecific antibodies (antiextractable nuclear antigens). We collected 90 samples from patients and 45 samples from healthy controls. Group I (SLE) ANAs were positive in 100% during the 1st T, 67% in the 2nd T, and 67% in the 3rd T, with various immunofluorescence patterns. In five patients, aCL antibodies were detected without a history of APS (one in 1st T, three in 2nd T, and one in 3rd T). Fetal loss was observed in two patients, in one of whom it was associated with nephritis, high titers of ANAs, and anti-dsDNA. Another patient had pulmonary hemorrhage with anti-dsDNA and aCL. In group II, all but one patient with primary APS were negative to ANAs. In secondary APS, by contrast, 6/8 patients (75%) had positive ANAs at least during the 1st T. All seven patients with primary APS and 6/8 with secondary APS had aCL during pregnancy. In 9/15 (60%) patients from the APS group with a history of previous fetal loss, aCL became negative during pregnancy and they had live births. The disappearance of aCL was associated with improved fetal survival (relative risk, or RR, 0.67). ANAs in the control group were positive in 7% at low titers, and all of them were negative for aCL. Despite treatment, ANAs are prevalent during pregnancy in SLE patients and APS secondary to SLE. During pregnancy in SLE, aCL titers may appear. Decreasing titers and/or disappearance of aCL correlated with improved fetal prognosis in a subset of patients with APS.

Bloqueo cardiaco completo secundario a intoxicación por cloroquina: informe de dos casos / Secondary complete cardiac block due to chloroquine intoxication: report of two cases

Se presentan dos casos, uno de cuarenta y otro de sesenta y cuatro años de edad con historia de artritis reumatoides seropositiva, quienes después de recibir tratamiento con 150 mg al día de cloroquina durante uno y cinco años respectivamente, desarrollaron bloqueo cardiaco completo que revirtió a ritmo sinusal entre 72 a 96 horas después de que el medicamento fue descontinuado. Dos monitores de Holter de 24 horas al primer y al tercer mes de seguimiento no mostraron alteraciones electrocardiográficas subsecuentes.

Importancia de las lesiones vasculares microangiopáticas en pacientes con nefritis lúpica / Lesions vascular microangiopathy in patients with systemic lupus erithematosus

Este reporte comprende el estudio histológico de 140 biopsias renales tomadas de 122 pacientes (109 mujeres y 13 varones) en quienes el diagnóstico de lupus eritematoso sistémico (LES) se estableció de acuerdo con los criterios del American College of Rheumatology (ACR) y el tiempo de evolución promedio fue de 3.5 años. En 103 se encontraron lesiones vasculares renales de uno o más tipos: necrosis, trombosis, leucocitoclasia, fibrosis, microangiopatía trombótica (MAT) y vasculitis necrosante. Se presenta la distribución por clase histológica y se analizan aquellos en quienes se encontró MAT. Se discute la importancia de la microangiopatía trombótica en LES como factor pronóstico y la posible relación clínica con anticuerpos anticardiolipina