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Background: Several recent clinical trials studied treatment adherence to methotrexate (MTX) and placebo in rheumatoid arthritis (RA) cases. However, no real-world studies on treatment adherence focus on phase-1 (P1) treatment with conventional synthetic (cs) disease-modifying anti-rheumatic drug (DMARD) monotherapy. Objectives: We investigated the 2-year continuity of P1 treatment in patients with RA who were DMARD-naïve and examined the factors influencing these retention rates. Methods: We assessed the eligibility of 934 patients with RA visiting our institution between 2013 and 2023. We excluded patients in whom treatment was started by a previous physician (n=520), to clarify the duration of the DMARD intervention, those who were administered the first DMARD in a clinical study(n=5), and those who received treatment deviating from the recommended EULAR management algorithm (n=22). We retrospectively examined continuity using Kaplan-Meier analysis for the MTX (MTX-G) and other csDMARD (DMARD-G) treatment arms performed in P1 for eligible subjects (n=386), with the following two dropout patterns: 1)P1 treatment continuation rates with dropouts for P1 treatment discontinuation for any reason at 2 years. 2)P1 treatment continuation rates with dropouts for transition to phase-2 (P2) treatment at 2 years. Additionally, factors influencing the P2 transition(P1→P2), such as the choice of first treatment, age at intervention, sex, response to treatment from the start of intervention to 13 weeks (early response), and risk factors in P2 (rheumatoid factor (RF), anti-CCP antibody (ACPA), high disease activity (HDA) at the first visit (DAS28ESR>5.1), and bone erosion (ERO) on radiography), were used in the COX regression analysis. Results: Treatment choice in P1 was made by the physician-in-charge, considering the comorbidities. Among the patients enrolled according to eligibility, 300 were in the MTX-G and 86 in the DMARD-G. The MTX-G included patients (n=12, 4.0%) with a history of other DMARD use within 2 weeks. The DMARD-G included the administration of salazosulfapyridine (82.6%), tacrolimus (10.9%), and other csDMARDs (8.8%). Treatment of patients transferred to P2 (n=209) included b/tsDMARD (add-on or switching) in 39.7%, add-on csDMARDs in 52.2%, and switching to csDMARD in 8.1%. Kaplan-Meier analysis showed that the continuation rates for P1 in the MTX-G and DMARD-G were 52.8% and 50.0% at Wk52, and 42.7% and 38.2% at Wk104, respectively, with no statistically significant differences in the initial drug choice. The continuation rates for P1→P2 were 54.0% and 51.5% at Wk52, and 44.4%and 42.9% at Wk104 in the MTX-G and DMARD-G, respectively, without statistically significant differences in the initial treatment choice. Reasons for P1→P2 transition included no response (0.9%), poor response (66.6%), loss of efficacy (21.5%), interstitial pneumonitis (1.4%), reduced eGFR (0.5%), liver dysfunction (1.9%), malignancy (0.5%), and others (10.5%). COX regression analysis of P1→P2 transition with candidate influencing factors as covariates showed a statistically significant difference (OR: 2.361; 95%CI 1.671–3.338, pConclusion: The first DMARD choice in the P1 treatment, considering complications, did not impact treatment continuity. However, MTX therapy has been shown to be more effective than other csDMARD in terms of treatment continuation rates and survival outcomes for P1→P2 patients. Therefore, the policy of recommending the use of MTX in the absence of contraindications, also supported by the EULAR recommendations, is likely to be maintained. As the treatment response up to 3 months after the treatment intervention influences P1→P2 transition, it is suggested that rheumatologists treating RA should follow the treat-to-target concept and appropriately assess disease activity monthly during the first 3 months of the initial treatment. Determining early P2 transition based on treatment response for up to three months may be useful in providing good outcomes for patients with RA. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Takafumi Hagiwara Asahi Kasei Pharma Corporation., Astellas Pharma Inc., AbbVie GK, Eli Lilly Japan K.K., CHUGAI PHARMACEUTICAL Co., LTD. Eisai Co., Ltd, AYUMI Pharmaceutical Corporation., Taisho Pharmaceutical Holdings., UCB Japan Co., Ltd., Mitsubishi Chemical Group Corporation., Japan Blood Products Organization., GlaxoSmithKline K.K., and Sanofi K.K., Yuuya Yano Japan Blood Products Organization., Shintarou Tsumura: None declared, Noriyuki Namura: None declared, Kazuya Kamada: None declared, Satoshi Kashiwagi Astellas Pharma Inc., UCB Japan Co. LtD., Otsuka Pharmaceutical Co., Ltd., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation., Eli Lilly Japan K.K., Asahi Kasei Pharma Corporation., and Mitsubishi Chemical Group Corporation., Tsukasa Matsubara Astellas Pharma Inc., Bristol-Myers Squibb., AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Gilead Sciences K.K., CHUGAI PHARMACEUTICAL CO., LTD. Eisai Co., Ltd, and AYUMI Pharmaceutical Corporation.
Hagiwara et al. (Sat,) studied this question.