FRI0080 Glucocorticoids and methotrexate have a synergistic working on decrease of rheumatoid arhtritis disease activity
Authors: M. C. De Rotte, P. H. De Jong, R. A. Quax, E. Den Boer, S. M. Pluijm, R. De Jonge, J. M. Hazes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent research has shown that response to glucocorticoids (GC) predicts the effectiveness of DMARD induction therapy including methotrexate (MTX).[1] Moreover, GC use has been associated with higher intracellular concentrations of methotrexate-polyglutamates (MTX-PG),[2] and higher MTX-PG concentrations were associated with lower disease activity in rheumatoid arthritis (RA).[3] If GC use is associated with higher MTX-PG concentrations, the association between MTX-PG concentrations and non-response may be modified by GC use. <h3>Objectives</h3> The objectives were to investigate whether MTX concentrations are associated with response and whether this association is modified by CG use. <h3>Methods</h3> This study included combined data of RA patients treated with MTX from 2 longitudinal cohorts: 285 from the tREACH study and 102 from the MTX-R study. We measured MTX with a tail of 1,2,3,4 and 5 glutamates in erythrocytes after 3 months of therapy using an LC-MS/MS assay. GC use was defined as use of oral or intramuscular GC therapy at start of treatment. As outcome measure for MTX response we defined disease activity score (DAS) 28 at 3 months. GC use, MTX-PG concentrations and their interaction terms (CGuse*MTX-PG concentrations) were tested for associations with DAS28 with an ANCOVA analysis. The analysis was corrected for gender, age, MTX-dose, baseline DAS28, and other DMARD use. <h3>Results</h3> Mean DAS28 decreased from 4.76 (SD=1.26) to 3.07 (SD=1.20) after 3 months. 49% of patients used glucocorticosteroids at baseline and the median total MTX-PG was 54 nmol/l (IR=42-70). MTX-PG1 (p=0.012), MTX-PG2 (p=0.001), MTX-PG3 (p=0.006) and total MTX-PG were negatively associated with DAS28. GC use was not associated with DAS28 (p=0.450). Patients with GC use had higher concentrations of MTX-PG3 (p=0.005), MTX-PG4 (p&lt;0.001) and MTX-PG5 (P&lt;0.001) than patients without GC treatment. The interactions between GC use and total MTX-PG was significantly associated with DAS28 (p=0.049). When data were stratified by CG use lower MTX-PG1 (p=0.004), MTX-PG2 (p=0.005) and total MTX-PG (p=0.008) were associated with non-response only in patients who did not use corticosteroids at baseline. In persons who used CGs no association was shown. <h3>Conclusions</h3> This study shows that MTX-PG concentrations were related to a lower DAS28. Furthermore we showed that GC use increases the accumulation speed of MTX-PG concentrations and thereby possibly potentiating the efficacy of MTX, resulting in a lower DAS28. The association between MTX-PGs and DAS28 depends on CG use. <h3>References</h3> de Jong PH, et al. Ann Rheum Dis. 2012 Oct 31; Stamp LK, et al. Arthritis Rheum. 2009 Aug;60(8):2248-56; Dervieux T, et al. Ann Rheum Dis. 2005 Aug;64(8):1180-5. <h3>Acknowledgements</h3> tREACH: Unrestricted grant from Pfizer bv. (0881-102217). RDJ: Dutch Arthritis Association (06-02-402 and 09-1-402). <h3>Disclosure of Interest</h3> None Declared