Heterogeneity Of Treatment Responses In Rheumatoid Arthritis Using Group Based Trajectory Models: Secondary Analysis Of Clinical Trial Data

Fowzia Ibrahim*, Ian C. Scott, David Scott, Salma Ayis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background
Traditionally rheumatoid arthritis (RA) trials classify patients as responders and non-responders; they ignore the potential range of treatment responses. Group Based Trajectory Models (GBTMs) provide a more refined approach. They identify patient subgroups with similar outcome trajectories. We used GBTMs to classify patients into subgroups of varying responses and explore factors associated with different responses to intensive treatment in a secondary analysis of intensive treatment in the TITRATE clinical trial.

Methods
The TITRATE trial enrolled 335 patients with RA: 168 patients were randomised to receive intensive management, which comprised monthly assessments including measures of the disease activity score for 28 joints (DAS28), treatment escalation when patients were not responding sufficiently and psychosocial support; 163 of these patients completed the trial. We applied GBTMs to monthly DAS28 scores over one year to these patients who had received intensive management. The control group had standard care and were assessed every 6 months; they had too few DAS28 scores for applying GBTMs.

Results
GBTMs identified three distinct trajectories in the patients receiving intensive management: good (n=40), moderate (n=76) and poor (n=47) responders. Baseline body mass index (BMI), disability, fatigue and depression levels were significantly different between trajectory groups. Few (10%) good responders were obese, compared to 38% of moderate, and 43% of poor responders (P=0.002). Few (8%) good responders had depression, compared to 14% moderate responders, and 38% poor responders (P
Conclusion
GBTMs identified three trajectories of disease activity progression in patients receiving intensive management for moderately active RA. Baseline variables like obesity and depression predicted different treatment responses. Few good responders needed biologic drugs; they responded to conventional DMARDs alone. GBTMs have the potential to facilitate precision medicine enabling patient-oriented treatment strategies based on key characteristics.
Original languageEnglish
JournalBMC Rheumatology
Publication statusAccepted/In press - Jun 2023

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