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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Chamaida
C
Plasencia
Immunology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Teresa
T
Jurado
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Alejandro
A
Villalba
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Diana
D
Peitedado
Immunology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Maria Teresa López
MT
Casla
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Laura
L
Nuño
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
María Gema
MG
Bonilla
Immunology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Ana
A
Martínez-Feito
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Emilio
E
Martín-Mola
Immunology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Dora
D
Pascual-Salcedo
Rheumatology Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) , Madrid , Spain.
Alejandro
A
Balsa
clinical efficacy; dose increase; infliximab; rheumatoid arthritis