THU0099 THE TIME REQUIRED TO ESCALATE THE DOSAGE OF METHOTREXATE TO THERAPEAUTIC LEVELS AFFECTS THE TREATMENT SUCCESS ACHIEVED DURING PHASE I OF THE TREATMENT ALGORITHM FOR RHEUMATOID ARTHRITIS RECOMMENDED BY THE EUROPEAN LEAGUE AGAINST RHEUMATISM
Authors: T. Hagiwara, K. Kamada, N. Namura
Journal: Annals of the Rheumatic Diseases (2020)

Background: In the treatment of rheumatoid arthritis (RA), methotrexate (MTX) monotherapy is undoubtedly the most cost-effective therapy available. However, no clear evidence exists for the adopted method of MTX usage, except for guidelines that have been formulated using empirical knowledge. Objectives: We aimed to retrospectively evaluate the treatment method used to administer MTX in order to identify factors influencing the success rate of MTX treatment in phase I of the European League Against Rheumatism (EULAR) recommendation in the treatment algorithm of RA. Methods: A total of 520 RA patients were considered for inclusion in this study, of whom 183 were eligible as they had been treated with MTX monotherapy from 2013 to 2018. The exclusion criteria included the following: unknown MTX prescription details (200 cases), deviation from the treatment algorithm i.e. use of a combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before MTX therapy (4 cases), and a long duration of MTX escalation that deviated from the treat-to-target concept (133 cases). Patients who received csDMARD monotherapy (including switching between csDMARDs) prior to MTX monotherapy were not excluded. The primary outcome was failed MTX monotherapy with transition to phase II. The escalation time to the required maximum therapeutic dose of MTX and the lower limit of the required maintenance therapeutic dose that resulted in successful MTX monotherapy was determined using the receiver operating characteristic (ROC) curve. Accordingly, previous results obtained from ROC curve analyses were categorized into two groups for regression analysis: patients who tolerated MTX monotherapy and those who failed MTX monotherapy. We performed a regression analysis on the background factors observed during their first visit to our department and two previously identified factors. The background factors included prognostically unfavourable factors related to joint destruction despite RA treatment (i.e. rheumatoid factor [RF] levels, anti-citrullinated peptide antibody [ACPA] levels, acute phase reactant levels, swollen joint counts, joint damage, and disease activity). Results: The background factors that were statistically different were age at onset, RF levels, ACPA levels, current dose and continuity of MTX therapy, glucocorticoid (GC) use, and time until first DMARD use. After this analysis, we determined to exclude GC use from subsequent analyses as it was found to be statistically different between age groups. Using the ROC analysis, we found that the escalation time to the maximum dose of MTX was 2.07 weeks. Further, logistic regression analysis was used to analyse each of the previously reported statistically significant factors. Statistical differences were observed in the age at onset and the escalation time of initial MTX induction therapy. We also performed a backward stepwise logistic regression analysis on the previous two factors and conventional risk factors related to joint destruction with RA treatment. Statistical difference was observed in the escalation time of initial MTX induction therapy. Furthermore, propensity score matching was performed by analysing the previously mentioned influencing factors and prognostically unfavourable factors of joint destruction using a backward stepwise logistic regression analysis. We identified statistical difference in the escalation time of MTX induction therapy (odds ratio: 1.957 [95% confidential interval: 1.036-3.697], p=.039). Conclusion: These results suggest that rapid escalation to the required MTX therapeutic dose, within 2.07 weeks, during initial RA treatment can shorten the time required to achieve the treatment target. By doing this, RA patients on MTX therapy in phase I may achieve a greater treatment responsive. Thus, the short escalation time is an important factor influencing successful MTX monotherapy in the RA treatment algorithm. Disclosure of Interests: None declared