SAT0122 HIGHER DOSES OF METHOTREXATE ASSOCIATED WITH DISCONTINUATION OF ORAL GLUCOCORTICOIDS AFTER INITIATION OF BIOLOGICAL DMARDS: A RETROSPECTIVE OBSERVATIONAL STUDY BASED ON DATA FROM A JAPANESE MULTICENTER REGISTRY STUDY
Authors: M. Suzuki, T. Kojima, N. Takahashi, S. Asai, K. Terabe, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2020)

Background: Glucocorticoids exert anti-inflammatory effects and are important drugs used to treat rheumatoid arthritis(1). We recommend glucocorticoid discontinuation as soon as possible because glucocorticoid caused several side effects, but many patients continue to take oral glucocorticoids long-term in daily clinical practice. The frequency of use of glucocorticoid has gradually declined, and there are several reports on discontinuation of glucocorticoid due to the initiation of biological disease-modifying antirheumatic drugs (bDMARDs)(2). However, there is no report showing the relation between discontinuation of glucocorticoid and MTX dose. Objectives: The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating bDMARDs. Methods: We established the large observational cohort, the Nagoya University orthopedic facility multicenter study (TBCR), and a total of 3119 patients used bDMARD and examined the status of oral glucocorticoid use at 52 weeks after initiating the 1 st bDMARD. In predictive analyses, the outcome variable was glucocorticoid discontinuation at 52 weeks after bDMARD initiation. Factors associated with baseline characteristics at bDMARD initiation were assessed with univariate and stepwise forward multivariate logistic regression analyses. This cohort study was not randomized. Propensity score (PS) matching was used to align patient backgrounds to avoid selection bias. Results: Subjects were 564 patients administered glucocorticoids and methotrexate (MTX) following initiation of the 1 st bDMARD (Figure 1). Mean DAS28-CRP at bDMARD initiation was 4.70 ± 1.16. Percentages of patients with low, moderate, and high disease activity as evaluated by DAS28-CRP at bDMARD initiation were 4.7%, 23.5%, and 71.8%, respectively. By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariate analysis identified age (odds ratio (OR), 0.98), MTX dose (OR, 1.11), and glucocorticoid dose (OR, 0.87) as factors independently associated with glucocorticoid discontinuation at the time of bDMARD initiation (Table 1). After adjusting for baseline characteristics using propensity score matching among patient groups administered MTX ≤ 8 mg/week and MTX &gt; 8 mg/week, 105 pairs remained. Among patients administered MTX &gt; 8 mg/week, 41.0% discontinued glucocorticoids. Among those administered MTX ≤ 8 mg/week, 22.9% discontinued glucocorticoids, with a significant difference between the two groups (Figure 2, P=0.007). Table 1. Factors associated with baseline characteristics at bDMARD initiation Continuation (n=400) Discontinuation (n=164) Univariate Odds ratio (95% CI) Multivariate Odds ratio (95% CI) Age, years 58.4 ± 12.9 54.3 ± 14.3 0.98 (0.97-0.99) * 0.98 (0.97-0.99) * Disease duration, years 9.4 ± 9.4 7.5 ± 8.5 0.98 (0.95-0.99) * – Female, % 80.3 81.1 1.06 (0.67-1.68) – DAS28-CRP 4.78 ± 1.15 4.50 ± 1.16 0.81 (0.69-0.96) * – Seropositivity, % 90.0 86.1 0.69 (0.38-1.25) – MTX dose, mg/week 7.7 ± 2.5 8.8 ± 3.0 1.16 (1.09-1.24) * 1.11 (1.03-1.21) * Glucocorticoid dose, mg/day 4.9 ± 2.1 4.3 ± 2.1 0.86 (0.78-0.95) * 0.87 (0.78-0.97) * TNF inhibitor use, % 88.8 85.4 0.74 (0.43-1.26) - Data are presented as mean ± standard deviation. Conclusion: Data from the TBCR revealed that, from a clinical perspective, glucocorticoid use decreased among RA patients treated with bDMARDs. Higher doses of MTX (&gt; 8 mg/week) at the time of bDMARD initiation were found to be associated with glucocorticoid discontinuation in patients treated with bDMARDs. In addition, we found that aggressive use of MTX was sufficient to fulfill the Treat-to-Target approach, demonstrating that glucocorticoid discontinuation is a viable option. References: [1]Smolen JS. Ann Rheum Dis. 2014;73(3):492-509. [2]Shimizu Y. Mod Rheumatol. 2018;28(3):461-7. Disclosure of Interests: Mochihito Suzuki Speakers bureau: Bristol-Myers Squibb, Eisai, and Asahi Kasei, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Kenya Terabe: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama