Latent Class Trajectory Modeling of 2‐Component Disease Activity Score in 28 Joints Identifies Multiple Rheumatoid Arthritis Phenotypes of Response to Biologic Disease‐Modifying Antirheumatic Drugs

Objective To determine whether using a reweighted disease activity score that better reflects joint synovitis, i.e., the 2‐component Disease Activity Score in 28 joints (DAS28) (based on swollen joint count and C‐reactive protein level), produces more clinically relevant treatment outcome trajectories compared to the standard 4‐component DAS28. Methods Latent class mixed modeling of response to biologic treatment was applied to 2,991 rheumatoid arthritis (RA) patients in whom treatment with a biologic disease‐modifying antirheumatic drug was being initiated within the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort, using both 4‐component and 2‐component DAS28 scores as outcome measures. Patient groups with similar trajectories were compared in terms of pretreatment baseline characteristics (including disability and comorbidities) and follow‐up characteristics (including antidrug antibody events, adherence to treatments, and blood drug levels). We compared the trajectories obtained using the 4‐ and 2‐component scores to determine which characteristics were better captured by each. Results Using the 4‐component DAS28, we identified 3 trajectory groups, which is consistent with previous findings. We showed that the 4‐component DAS28 captures information relating to depression. Using the 2‐component DAS28, 7 trajectory groups were identified; among them, distinct groups of nonresponders had a higher incidence of respiratory comorbidities and a higher proportion of antidrug antibody events. We also identified a group of patients for whom the 2‐component DAS28 scores remained relatively low; this group included a high percentage of patients who were nonadherent to treatment. This highlights the utility of both the 4‐ and 2‐component DAS28 for monitoring different components of disease activity. Conclusion Here we show that the 2‐component modified DAS28 defines important biologic and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.