Remission or low disease activity at pregnancy onset are linked to improved foetal outcomes in women with systemic lupus erythematosus: results from a prospective observational study.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients show variably increased risk for pregnancy complications. We analysed pregnancy outcomes (foetal and maternal), patterns of disease activity and use of medications in a contemporary Caucasian SLE population. METHODS: Prospective observational study, involving hospital units and private rheumatologists in Greece, of incident pregnancies (period 2015-2018) in women with SLE. Clinical and obstetrical monitoring was performed at regular intervals up to 9 months post-partum. Regression and mixed model analyses were used to determine predictors for adverse foetal outcomes and flares. RESULTS: We monitored 82 pregnancies in 64 SLE patients. Foetal loss, prematurity and small for gestational age neonate occurred at 15.8%, 34.1% and 8.5%, respectively; 53.7% of pregnancies were complicated with at least one adverse outcome. Patients with antiphospholipid antibodies (aPL) had increased risk (odds ratio [OR] 5.67, p=0.015), whereas those at low disease activity at pregnancy onset were protected (OR 0.20, p=0.024) against foetal complications. Persistent activity and glucocorticoid intake during pregnancy also predicted poor foetal outcomes. SLE patients experienced an average 1.08 mild/moderate and 0.27 severe flares. The latter occurred more frequently post-partum, in patients with alopecia (OR 8.92, p=0.003), hypocomplementaemia (OR 10.34, p=0.038) and nephritis (OR 7.32, p=0.052). Lupusactivity post-labour was paralleled by decreased use of hydroxychloroquine, glucocorticoids and azathioprine. CONCLUSIONS: In SLE women, foetal complications are common especially in the presence of aPL and increased activity, which corroborates the importance of pregnancy planning and tight disease control at pregnancy onset. Flares, mostly mild or moderate, can occur both during and after pregnancy.

In early arthritis patients, high HAQ at baseline and DAS28 at three months predict suboptimal outcomes at two years: a retrospective cohort study.

OBJECTIVES: Early arthritis clinics (EAC) aim to improve rheumatoid arthritis (RA) outcomes by tailoring treatment targeting to remission. Our aim was to analyse disease course and relevant predictors over 2 years in early arthritis; we also assessed the applicability of the "treat-to-target approach" in a real-life EAC. METHODS: Patients with early arthritis recruited at the EAC of the University Hospital of Heraklion were followed prospectively according to a follow-up protocol for two years, without implementing a pre-specified treatment protocol, to capture real-life practices. Early predictors of "suboptimal outcomes" (high disease activity or HAQ>1.0 at 2 years) and biologic DMARD (bDMARD) initiation were evaluated with multivariate logistic regression. Intensification of treatment at 3 and 6 months and subsequent long-term outcome were also assessed. RESULTS: 251 patients [RA (n=188), undifferentiated arthritis (n=63)] were included. Although both DAS28 and HAQ at 2 years improved significantly compared to baseline in RA patients [mean (SD) DAS28 and median (IQR) HAQ 3.70 (1.32) and 0.44 (0.75) at 2 years, p<0.001 for both compared to baseline], 43.7% still had moderate and 18.8% high disease activity. The most powerful predictor of suboptimal outcomes or bDMARD initiation in RA was high disease activity at three months (adjusted odds ratio 2.22 and 2.62, respectively). At three and six months 72.8% and 62.4% of patients with medium/high disease activity received treatment intensification, which resulted in significant decrease in disease activity at 2 years (p<0.001 for ΔDAS28). CONCLUSIONS: DAS28 at three months was the most powerful predictor of suboptimal disease outcome during a 2-year follow-up in early RA. Despite significant DAS reductions, more than 50% of patients have active disease at two years. Failure to fully implement the treat-to-target strategy in our cohort could account for the low remission rates.

Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance.

INTRODUCTION: Prevalence of insulin resistance and the metabolic syndrome has been reported to be high in rheumatoid arthritis (RA) patients. Tumor necrosis factor (TNF), a pro-inflammatory cytokine with a major pathogenetic role in RA, may promote insulin resistance by inducing Ser312 phosphorylation (p-Ser312) of insulin receptor substrate (IRS)-1 and downregulating phosphorylated (p-)AKT. We examined whether anti-TNF therapy improves insulin resistance in RA patients and assessed changes in the insulin signaling cascade. METHODS: Prospective study of RA patients receiving anti-TNF agents (infliximab, n = 49, adalimumab, n = 11, or etanercept, n = 1) due to high disease activity score in 28 joints (DAS28 > 5.1). A complete biochemical profile was obtained at weeks 0 and 12 of treatment. Insulin resistance, insulin sensitivity and pancreatic beta cell function were measured by the Homeostasis Model Assessment (HOMA-IR), the Quantitative Insulin Sensitivity Check Index (QUICKI) and the HOMA-B respectively. Protein extracts from peripheral blood mononuclear cells were assayed by western blot for p-Ser312 IRS-1 and p-AKT. RA patients treated with abatacept (CTLA4.Ig) were used as a control group for insulin signaling studies. RESULTS: At study entry, RA patients with high insulin resistance (HOMA-IR above median) had significantly higher mean DAS28 (P = 0.011), serum triglycerides (P = 0.015), and systolic blood pressure levels (P = 0.024) than patients with low insulin resistance. After 12 weeks of anti-TNF therapy, patients with high insulin resistance demonstrated significant reduction in HOMA-IR (P < 0.001), HOMA-B (P = 0.001), serum triglycerides (P = 0.039), and increase in QUICKI (P < 0.001) and serum HDL-C (P = 0.022). Western blot analysis in seven active RA patients with high insulin resistance showed reduction in p-Ser312 IRS-1 (P = 0.043) and increase in p-AKT (P = 0.001) over the study period. In contrast, the effect of CTLA4.Ig on p-Ser312 IRS-1 and p-AKT levels was variable. CONCLUSIONS: Anti-TNF therapy improved insulin sensitivity and reversed defects in the insulin signaling cascade in RA patients with active disease and high insulin resistance. The impact of these biochemical changes in modifying cardiovascular disease burden in active RA patients remains to be seen.

Metabolic syndrome in rheumatic diseases: epidemiology, pathophysiology, and clinical implications.

Subjects with metabolic syndrome--a constellation of cardiovascular risk factors of which central obesity and insulin resistance are the most characteristic--are at increased risk for developing diabetes mellitus and cardiovascular disease. In these subjects, abdominal adipose tissue is a source of inflammatory cytokines such as tumor necrosis factor-alpha, known to promote insulin resistance. The presence of inflammatory cytokines together with the well-documented increased risk for cardiovascular diseases in patients with inflammatory arthritides and systemic lupus erythematosus has prompted studies to examine the prevalence of the metabolic syndrome in an effort to identify subjects at risk in addition to that conferred by traditional cardiovascular risk factors. These studies have documented a high prevalence of metabolic syndrome which correlates with disease activity and markers of atherosclerosis. The correlation of inflammatory disease activity with metabolic syndrome provides additional evidence for a link between inflammation and metabolic disturbances/vascular morbidity.