AB0277 ASSOCIATION BETWEEN INTRA-ERYTHROCYTE METHOTREXATE POLYGLUTAMATE CONCENTRATION AND CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS IN PATIENTS TREATED WITH METHOTREXATE INJECTABLE SUBCUTANEOUSLY
Authors: M. Poudret, M. Norman, S. Hodin, A.S. Amouzougan, K. Boussoualim, A. Coassy, T. Neel, T. Thomas, X. Delavenne, H. Marotte
Journal: Annals of the Rheumatic Diseases (2021)

Background: Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA). Due to its short half-life, blood MTX dosage is not performed in current practice. Erythrocyte MTX-polyglutamate (MTX-PG), which penetrates into the red blood cells, would be correlated with the area under the MTX curve and would be more accessible for dosing. When treatment is initiated, its concentration correlates with efficacy and therapeutic adherence. Objectives: To determine the interest of erythrocyte MTX-PG dosage in case of failure of 1 st line MTX treatment. Methods: In this single-centre cross-sectional study, RA patients presenting for consultation at the Saint-Etienne University Hospital, with a stable dose of MTX for more than 3 months at least 15 mg/week subcutaneously with either clinical remission (DAS28&lt;2.6) or active disease (DAS28&gt;3.2) were included between July 2 nd 2018 and May 28 th 2020. In order to assess therapeutic compliance, the patient completed the compliance questionnaire of Rheumatology (CQR) questionnaire. The determination of erythrocytic MTX-PG was performed on a 5 mL blood sample by liquid chromatography method for the determination of the different PG forms. Results: Sixty patients were included, 34 in the active RA group and 26 in the RA group in remission. One patient withdrew his consent. Only 16% of patients were observed with a CQR score &gt; 80%. Patients in remission were leaner with a longer duration of disease and MTX treatment. The sex ratio, RA status, creatinine clearance and MTX dose was not different in both groups. The CQR was better in the remission group than in the active RA group. However, total MTX-PG was not different in the two groups. The same results were observed for the different forms of MTX-PG 1, 2, 3 or 4. In contrast, in the remission PR group, total MTX-PG or MTX-PG2, 3, 4 and 5 correlated inversely with BMI while MTX-PG3 correlated positively with BMI in the active PR group. In the active PR group, MTX-PG5 correlated with MTX dose. Conclusion: MTX-PG dosage is not a biomarker of good response to MTX in our study. However, compliance is a key factor to be considered in RA with active disease in adapting patient management. References: [1]Pasma A, Boer E den, Spijker A van ’t, Timman R, Bemt B van den, Busschbach JJV, et al. Nonadherence to disease modifying antirheumatic drugs in the first year after diagnosis: comparing three adherence measures in early arthritis patients. Rheumatology 2016;55:1812–1819. [2]Haandel L van, Becker ML, Leeder JS, Williams TD, Stobaugh JF. A novel high-performance liquid chromatography/mass spectrometry method for improved selective and sensitive measurement of methotrexate polyglutamation status in human red blood cells. Rapid Commun Mass Spectrom RCM 2009;23:3693–3702. [3]Dervieux T. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005;64:1180–1185. Disclosure of Interests: Marion POUDRET: None declared, Myriam Norman: None declared, Sophie Hodin: None declared, Adamah Stanislas AMOUZOUGAN: None declared, Karima BOUSSOUALIM: None declared, Astrid Coassy: None declared, Tiphany Neel: None declared, THIERRY THOMAS: None declared, Xavier DELAVENNE: None declared, Hubert MAROTTE Speakers bureau: Pfizer, Nordic, Paid instructor for: Amgen, Consultant of: Novartis, Grant/research support from: Nordic