Twelve-Year Retention Rate of First-Line Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: Real-Life Data From a Local Registry.

OBJECTIVE: To evaluate the 12-year survival of the first tumor necrosis factor inhibitor (TNFi) treatment in a cohort of rheumatoid arthritis (RA) patients, comparing the between-groups discontinuation rates for infliximab, etanercept, and adalimumab. METHODS: RA patients treated with their first TNFi were investigated from a local registry. Before and after adjusting for propensity scores, overall and by individual TNFi 12-year drug retention was evaluated. Drug survival rates were calculated using the Kaplan-Meier method and compared by the Cox extended model. Subanalyses were performed according to concomitant methotrexate (MTX) and discontinuation reasons. RESULTS: Of 583 patients, 222 were treated with infliximab, 179 with etanercept, and 182 with adalimumab; 33.7% and 26% discontinued the first TNFi because of inefficacy or adverse events, respectively. The overall 12-year drug survival rate for the unmatched population was 23.4%. In the propensity score-adjusted population, the hazard ratio (HR) for treatment discontinuation was significantly greater for adalimumab and infliximab versus etanercept (HR 2.89 [95% confidence interval (95% CI) 2.2-3.78] and HR 2.56 [95% CI 1.92-3.4], respectively), and no difference was found between and for adalimumab versus infliximab (HR 1.16 [95% CI 0.91-1.47]). The incidence of withdrawal due to secondary inefficacy was stable from 3 to 12 years for etanercept, but progressively increased for the monoclonal antibodies. Concomitant MTX significantly increased the survival of both adalimumab and etanercept (HR 1.48 [95% CI 1.18-1.86]). CONCLUSION: The overall 12-year drug survival rate was 23.4%, being significantly higher for etanercept than adalimumab and infliximab. Etanercept discontinuations for inefficacy did not increase from 3 to 12 years. Concomitant MTX increased adalimumab and etanercept drug survival.

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs.

Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease affecting several organs. Although the management of lupus patients has improved in the last years, several aspects still remain challenging. More sensitive and specific biomarkers for an early diagnosis as well as for monitoring disease activity and tissue damage are needed. Genome-wide association and gene mapping studies have supported the genetic background for SLE susceptibility. However, the relatively modest risk association and the studies in twins have suggested a role for environmental and epigenetic factors, as well as genetic-epigenetic interaction. Accordingly, there is evidence that differences in DNA methylation, histone modifications, and miRNA profiling can be found in lupus patients versus normal subjects. Moreover, impaired DNA methylation on the inactive X-chromosome was suggested to explain, at least in part, the female prevalence of the disease. Epigenetic markers may be help in fulfilling the unmet needs for SLE by offering new diagnostic tools, new biomarkers for monitoring disease activity, or to better characterize patients with a silent clinical disease but with an active serology. Anti-DNA, anti-phospholipid, and anti-Ro/SSA autoantibodies are thought to be pathogenic for glomerulonephritis, recurrent thrombosis and miscarriages, and neonatal lupus, respectively. However, tissue damage occurs occasionally or, in some patients, only in spite of the persistent presence of the antibodies. Preliminary studies suggest that epigenetic mechanisms may explain why the damage takes place in some patients only or at a given time.