The sequence of disease-modifying anti-rheumatic drugs: pathways to and predictors of tocilizumab monotherapy
Journal article, 2021

Background: There are numerous non-biologic and biologic disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA). Typical sequences of bDMARDs are not clear. Future treatment policies and trials should be informed by quantitative estimates of current treatment practice. Methods: We used data from Corrona, a large real-world RA registry, to develop a method for quantifying sequential patterns in treatment with bDMARDs. As a proof of concept, we study patients who eventually use tocilizumab monotherapy (TCZm), an IL-6 antagonist with similar benefits used as monotherapy or in combination. Patients starting a bDMARD were included and were followed using a discrete-state Markov model, observing changes in treatments every 6 months and determining whether they used TCZm. A supervised machine learning algorithm was then employed to determine longitudinal patient factors associated with TCZm use. Results: 7300 patients starting a bDMARD were followed for up to 5 years. Their median age was 58 years, 78% were female, median disease duration was 5 years, and 57% were seropositive. During follow-up, 287 (3.9%) reported use of TCZm with median time until use of 25.6 (11.5, 56.0) months. Eighty-two percent of TCZm use began within 3 years of starting any bDMARD. Ninety-three percent of TCZm users switched from TCZ combination, a TNF inhibitor, or another bDMARD. Very few patients are given TCZm as their first DMARD (0.6%). Variables associated with the use of TCZm included prior use of TCZ combination therapy, older age, longer disease duration, seronegative, higher disease activity, and no prior use of a TNF inhibitor. Conclusions: Improved understanding of treatment sequences in RA may help personalize care. These methods may help optimize treatment decisions using large-scale real-world data.

Rheumatoid arthritis




Daniel H. Solomon

Brigham and Women's Hospital

Chang Xu

Brigham and Women's Hospital

Jamie Collins

Brigham and Women's Hospital

Seoyoung C. Kim

Brigham and Women's Hospital

Elena Losina

Brigham and Women's Hospital

Vincent Yau


Fredrik Johansson

Chalmers, Computer Science and Engineering (Chalmers), Data Science

Arthritis Research and Therapy

1478-6354 (ISSN) 14786362 (eISSN)

Vol. 23 1 26

Subject Categories

Pharmaceutical Sciences

Immunology in the medical area

Rheumatology and Autoimmunity

Areas of Advance

Health Engineering



More information

Latest update