Abstract
Background:Despite remarkable progress in therapy, not a few patients with rheumatoid arthritis (RA) have not achieved treatment target. Various factors can be ascribed to difficult-to-treat RA, however, little is known about their characteristics.Objectives:To clarify characteristics of patients with difficult-to-treat RA in real-world.Methods:We reviewed all consecutive RA patients in Keio University Hospital between 2016 and 2017 and collected medical information. We defined patients in moderate disease activity and high disease activity according to disease activity score for 28 joints (DAS28) at the last visit despite more than one year treatment for RA as difficult-to-treat RA and analyzed their clinical characteristics.Results:A total of 1693 patients with RA were enrolled in the analysis. The mean age at the last visit was 64 years old, female was 83%, and the mean disease duration was 11.9 years. Rheumatoid factor and anti-cyclic citrullinated peptide were positive for 76% and 75% of the patients, respectively. The current treatment were conventional synthetic disease modifying anti-rheumatic drugs in 73%, biologic agents or janus kinase (JAK) inhibitors in 57%, and glucocorticoids in 13%. Disease activity according to DAS28 was remission in 65%, low disease activity in 21%, and moderate/high disease activity in 14%, which was defined as difficult-to-treat RA. Characteristics of difficult-to-treat RA were the mean age of 70 years old, female of 89%, and the mean disease duration of 14.8 years. The current treatments were conventional synthetic disease modifying anti-rheumatic drugs alone in 40.7%, biologic agents or JAK inhibitors in 55.8%, and glucocorticoids in 29.0%. The causes of difficult-to-treat RA were unresponsiveness to several biologic agents and/or JAK inhibitors in 22.9%, comorbidities in 33.8%, and personal reasons in 39.8% (costs in 35.9%, low adherence in 4.3%, concerns about possible adverse reaction of drugs in 54.3% and high patient global assessment in 5.4%). Patient characteristics were significantly different between the causes; age at RA onset (51 vs 61 vs 51 years, p<0.001), current age (65 vs 77 vs 66 years, p<0.001), estimated glomerular filtration rate (75 vs 61 vs 73 mL/min/1.73m2, p<0.001), tender joint count (3.4 vs 1.6 vs 2.1, p=0.005), swollen joint count (3.1 vs 1.6 vs 2.9, p=0.003), evaluator global assessment (21 vs 14 vs 16 mm, p=0.03), health assessment questionnaire-disability index (1.3 vs 1.3 vs 0.9, p=0.005), a history of serious infection (28 vs 41 vs 13%, p<0.001) and rheumatic disease comorbidity index (1.2 vs 2.2 vs 0.9, p<0.001).Conclusion:There are still 14% of patients with RA were difficult-to-treat in real world in spite of intensive treatment. Their characteristics are distinct by the cause of difficulty to treat, suggesting the approach to difficult-to-treat RA should be personalized.
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