Predictors of Treatment Change Among Patients with Rheumatoid Arthritis Treated with TNF Inhibitors as First-Line Biologic Agent in the USA: A Cohort Study from Longitudinal Electronic Health Records

Background Previous observational studies utilizing administrative claims data have largely been unable to consider clinical factors that may be related to patterns of drug use among patients with rheumatoid arthritis (RA). Objective To understand predictors of treatment changes following initiation of a tumor necrosis factor inhibitor (TNFi) using nation-wide electronic health record (EHR) data in the USA. Methods The Optum Immunology Condition EHR data (01/01/2011-09/30/2019) was used to identify a population of adult patients with RA initiating a TNFi as the first line biologic disease-modifying anti-rheumatic drug (DMARD). The primary outcome was any treatment change during the 1-year post-index period defined as cycling to a different TNFi or switching to non-TNFi biologic or targeted synthetic DMARDs. Secondary outcomes were the individual components of TNFi cycling and switching, examined separately. To identify predictors of DMARD treatment changes, we used a least absolute shrinkage and selection operator (LASSO) regression model. Model c-statistics and odds ratios (ORs, 95% confidence intervals (CIs)) of predictors were reported. Results We identified 24,871 patients with RA who initiated a TNFi. The mean age was 55.5 (+/- 13.7) years and 77.2% were female. Among the TNFi initiators, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Predictors that are associated with higher likelihood of TNFi cycling or switching included female gender (OR: 1.26, 95% CI: 1.16-1.36) and glucocorticoid use (OR: 1.30, 95% CI: 1.21-1.40). In contrast, inflammatory bowel disease (OR: 0.62, 95% CI: 0.48-0.78), psoriasis (OR: 0.82, 95% CI: 0.70-0.95), recent use of methotrexate (OR: 0.89, 95% CI: 0.81-0.97), and vitamin D intake (OR: 0.92, 95% CI: 0.85-0.99) were negatively associated with TNFi cycling or switch. Conclusions Gender, glucocorticoid use, inflammatory bowel disease, psoriasis, and vitamin D intake were identified as significant predictors of TNFi cycling or switching for TNFi initiators in the RA population. Predicting treatment change remains challenging even with large detailed EHR data. Plain Language Summary This study aimed to identify key determinants of treatment changes among patients with rheumatoid arthritis (RA) initiating a tumor necrosis factor inhibitor (TNFi) as their first-line biologic disease-modifying antirheumatic drug (DMARD) in routine care settings using a US nation-wide longitudinal electronic health record (EHR). Among 24,871 patients with RA who initiated a TNFi, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Female patients and those who used glucocorticoids were more likely to experience TNFi cycling or switching, whereas inflammatory bowel disease, psoriasis, recent methotrexate use, and vitamin D intake were negatively associated with the outcome. However, predicting treatment change remains challenging even with larger detailed EHR data potentially due to unmeasured factors such as prescriber's preference or patient's belief in the medication.

Automated summary

This study used nationwide electronic health record (EHR) data in the USA to identify predictors of treatment changes among rheumatoid arthritis (RA) patients initiating a tumor necrosis factor inhibitor (TNFi). The study found that female patients and those who used glucocorticoids were more likely to experience TNFi cycling or switching. Conversely, inflammatory bowel disease, psoriasis, recent methotrexate use, and vitamin D intake were negatively associated with treatment changes.