Background:A definition of difficult-to-treat rheumatoid arthritis (D2T RA) was recently proposed by the European League Against Rheumatism (EULAR) [1]. However, information on the incidence rates of D2T RA in real-world clinical practice is lacking.Objectives:The aim of this retrospective cross-sectional study was to evaluate the incidence rates of D2T RA in clinical practice in Japan.Methods:Data from the Toyohashi RA database (TRAD) was used. The TRAD is a collection of single-center retrospective data. Patients with RA who fulfilled the following three requirements were included in this study: (1) had been treated with >1 biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD); (2) >1 year had passed since b/tsDMARD treatment was initiated; and (3) regularly visited our institute at the time of investigation. The number of targeted patients was 363. The criteria of D2T RA used in this study were modified from the EULAR definition for simplification of the investigation as follows: (a) ≥2 b/t DMARDs with different mechanisms of action had been administered; (b) at least moderate disease activity (DAS28-ESR > 3.2 or clinical disease activity index [CDAI] > 10) at the time of investigation; and (c) 7.5-mg/day of prednisolone (PSL) or more was administered at the time of investigation. In this study, D2T RA was defined as criteria (a) + (b) or (a) + (c) or (a) + (b) + (c). The 363 patients were categorized into four groups as follows: group A, DT2 RA; group B, patients with RA who had been treated with ≥2 b/tsDMARDs and did not fulfill the D2T RA definition; group C, RA patients who had been treated with one kind of b/tsDMARD with the same mechanism of action (e.g., two kinds of tumor necrosis factor inhibitors) and fulfilled either or both criteria (b) and (c); and group D, patients with RA who had been treated with one kind of b/tsDMARD with the same mechanism of action (e.g., a tumor necrosis factor inhibitors or two interleukin 6 inhibitors) and did not fulfill either or both criteria (b) and (c). The incidence rates of D2T RA were calculated, and the patients’ characteristics at the time of initiation of the b/tsDMARD treatment were compared between the groups.Results:The number of patients in groups A, B, C, and D were 34, 53, 94, and 182, respectively. Of all the patients included in this study, 9.4% were categorized into group A, those with D2T RA, and 39.1% were treated with ≥2 b/tsDMARDs and categorized into group A (Fig 1). The patients’ characteristics were as follows (group A/B/C/D): mean age (57.1/54.3/61.4/56.2 years), RA duration (10.0/6.7/13.8/8.2 years), %Steinbrocker stage III+IV (%; 84.0/60.0/77.3/54.3), %Steinbrocker class 3 + 4 (%; 68.0/33.3/43.4/23.0), methotrexate (MTX) concomitant rate (%; 79.4/92.5/74.5/91.8), PSL concomitant rate (%; 91.2/52.8/55.3/43.4), DAS28-ESR score (5.5/5.0/5.5/4.7), and CDAI score (12.3/13.7/22.7/16.9). There were statistically significant differences in RA duration, %stage III+IV, %class 3 + 4 and PSL concomitant rate between group A and B.Conclusion:D2T RA occurred in 9.4% of patients treated with b/tsDMARDs. Incidence rate was increased to 39.1% after the treatment with ≥2 b/tsDMARDs. The patients with D2T RA tended to be older, have a long RA duration, be treated without concomitant MTX, be treated with concomitant PSL, and have higher disease activity at the time of starting the b/tsDMARD treatment. The baseline patient characteristics in group C were similar to those in group A. In the future, we suggest that patients with D2T RA be included in group C.References:[1]Nagy et al. Ann Rheum Dis 2021; 80: 31-35.Disclosure of Interests:None declared
Head-to-head comparison of the safety of tocilizumab and tumor necrosis factor inhibitors in rheumatoid arthritis patients (RA) in clinical practice: results from the registry of Japanese RA patients on biologics for long-term safety (REAL) registry