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

Abstract

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.

Analyzing the risk of osteoporosis and fracture in rheumatoid arthritis patients who have been treated with various biologics

“…Therefore, we placed medications, tocilizumab, and Janus kinase (JAK) inhibitors, together into one subgroup as medications that could be used as monotherapy, which were named other bDMARDs, in our analysis. Tocilizumab 22,23 and the target synthetic DMARDs, 24 for example, small molecules of medication, could be used as monotherapy which has been well documented. A combination of T‐ or B‐cell modulating therapies was demonstrated with the effect of adjusting adaptive immunity against osteoporosis development and fracture incidence in RA patients 25,26 …”

Artificial Intelligence in Rheumatoid Arthritis: Current Status and Future Perspectives: A State-of-the-Art Review

“…Predicting risk of needing treatment step up to tocilizumab in patients who do not respond to initial therapy is another example of applications of AI in monitoring disease course in RA. A logistic regression model [ 141 ] showed that higher age and remission CDAI were the most important risk and protective factors for tocilizumab monotherapy, respectively (OR = 1.04 and 0.17, respectively) when excluding other treatments as variables. For any tocilizumab use (either monotherapy or in combination), the highest and lowest ORs belonged to the number of comorbidities (OR = 1.16) and remission CDAI (OR = 0.20) (excluding other treatments as factors).…”

“…Table 8 summarizes studies implementing ML and DL for monitoring disease course and predicting prognosis [ 79 , 137 , 138 , 140 , 141 , 146 , 147 , 149 , 157 – 166 ].…”

Patterns in the sequential treatment of rheumatoid arthritis patients starting a b/tsDMARD: 10-year experience from a US-based registry

“…For example, a transition from a TNFi to a non-TNFi b/tsDMARD appears the same in a Sankey diagram regardless of previous treatments. A different set of studies have focused on pathways to a particular type of therapy, for example tocilizumab monotherapy (14) or therapies with baricitinib (15), but they do not summarize the entire treatment strategy across the disease course.…”