FRI0080 Glucocorticoids and methotrexate have a synergistic working on decrease of rheumatoid arhtritis disease activity. (23rd January 2014)

• Record Type: Journal Article
• Authors: De Rotte, M. C.; De Jong, P. H.; Quax, R. A.; Den Boer, E.; Pluijm, S. M.; De Jonge, R.; Hazes, J. M.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A396
• Page End: A396
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.1207
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: 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. Objectives: The objectives were to investigate whether MTX concentrations are associated with response and whether this association is modified by CG use. Methods: 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. Results: 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<0.001) and MTX-PG5 (P<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. Conclusions: 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. References: 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. Acknowledgements: tREACH: Unrestricted grant from Pfizer bv. (0881-102217). RDJ: Dutch Arthritis Association (06-02-402 and 09-1-402). Disclosure of Interest: None Declared