Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis.

BACKGROUND: Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. OBJECTIVES: This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. METHODS: This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). RESULTS: A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. CONCLUSIONS: In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.

Pleural fluid cell-free DNA in parapneumonic pleural effusion.

OBJECTIVES: To measure the accuracy of pleural fluid cell-free DNA (cfDNA) concentration for diagnosis of parapneumonic pleural effusions (PPE). DESIGN AND METHODS: We studied pleural fluids obtained by thoracocentesis in patients with pleural effusion. DNA was automatically extracted from pleural fluid using the MagNa Pure Compact instrument (Roche Diagnostics), and was measured by a real-time quantitative PCR assay for the ß-globin gene using a Light-Cycler 480 Real-Time PCR instrument (Roche Diagnostics). Patients were classified into two groups according to the etiology of pleural effusion: PPE and NOT PPE. The diagnostic accuracy was determined using receiver operating characteristic (ROC) techniques by analyzing the area under the ROC curve (AUC). RESULTS: We studied 78 patients with ages between 1 and 86 years old (median=64). Sixteen patients were PPE and 62 were NOT PPE (24 transudative, 30 malignant and 8 other etiology). Pleural fluid cfDNA concentration was higher in patients with PPE (median=46,240 ng/mL) than in those with NOT PPE (median=224 ng/mL). The AUC value was 0.907 (p<0.0001) and the optimal cut-off value was 6740 ng/mL exhibiting 87.5% sensitivity and 80.6% specificity. Also, there were significant differences between transudative and exudative effusions according to pleural fluid cfDNA concentration (p<0.0001). The AUC value was 0.994 and the optimal cut-off value was 162ng/mL exhibiting 100% sensitivity and 96.3% specificity. CONCLUSIONS: Pleural fluid cfDNA concentration showed high accuracy for diagnosis of PPE and to discriminate between transudative and exudative effusions.