Effect of Infliximab Dose Increase in Rheumatoid Arthritis at Different Trough Concentrations: A Cohort Study in Clinical Practice Conditions

Chamaida Plasencia, Teresa Jurado, Alejandro Villalba, Diana Peitedado, Maria Teresa López Casla, Laura Nuño, María Gema Bonilla, Ana Martínez-Feito, Emilio Martín-Mola, Dora Pascual-Salcedo, Alejandro Balsa

Evidence supporting treatment intensification in rheumatoid arthritis (RA) is limited and controversial. We explored outcomes of infliximab dose increases and accounted for pre-existing trough levels in patients with active RA. This study was a retrospective study of 42 RA patients who received increased infliximab following an insufficient response (DAS28 >3.2). Serum concentrations of infliximab and antibodies to infliximab (ATI) and DAS28 and EULAR clinical response parameters were recorded for 1 year. Analyses were performed in three patient groups that were defined by infliximab serum concentration prior to treatment enhancement: no detectable, low (<1.1 μg/mL) or high (≥1.1 μg/mL) drug levels. No circulating infliximab was detected in 20 patients (47.6%), but 13 (31%) and 9 (21.4%) patients exhibited low and high levels, respectively. ATI was only detected in patients with no detectable drug levels because the drug interferes with ELISA. DAS28 disease activity globally showed a modest improvement after dose escalation, but this improvement did not persist after 6 and 12 months. Infliximab serum levels increased significantly in the high group (p = 0.016), but no increase was achieved in the low and no detectable groups. The three study groups exhibited similar disease activity over time, and no improvement was observed in the non-responder EULAR rates. These results suggest that the efficacy of an infliximab dose increase is limited, and the response is independent of the infliximab trough serum concentration that is achieved prior to escalation.