Background/Purpose: Tocilizumab (TCZ) efficacy and safety in rheumatoid arthritis (RA) have been well established by numerous phase 3 and 4 studies and observational studies. The purpose of the present analysis was to explore the extent to which disease duration, inflammation, disease burden, and other baseline factors explain variations in outcomes in studies of RA patients treated with TCZ

Methods: This was a pooled analysis of methotrexate-inadequate responding (IR)/conventional synthetic (cs) DMARD-IR patients with RA allocated to TCZ (intravenous or subcutaneous, monotherapy + combination therapy) in phase 3 and 4 studies. Endpoints were change from baseline to week 24 in Clinical Disease Activity Index (CDAI) and quality of life (Health Assessment Questionnaire–Disability Index [HAQ-DI]) and week 24 ACR50 and CDAI remission (≤2.8). Using a combination of clinically informed and mathematically driven variable selection techniques, models (with study included as a random effect to account for intracorrelation of observations within each study) were built to optimize fit and explain outcome variance. Analysis of covariance and logistic regression were used for CDAI/HAQ-DI change from baseline and for ACR50/CDAI remission, respectively.

Results: The analyses were performed on 5462 patients from 12 studies. Analysis of baseline characteristics (before TCZ administration) revealed that patients with longer disease duration had been exposed to more csDMARDS and had worse HAQ-DI than patients with shorter disease duration. Statistical modeling of clinical outcomes showed that disease duration accounted for <2% of the variation in HAQ-DI and CDAI change from baseline. Baseline CDAI explained 32% of the variation in CDAI change from baseline. Patients with higher baseline values tended to have greater improvements, likely due to having more “room” for improvement and to a higher risk for regression to the mean resulting from the fact that inclusion criteria for most trials required defined thresholds of disease activity, including joint counts. Baseline HAQ-DI, neither an inclusion criterion itself nor influenced by other inclusion criteria, explained 15% of the variation in HAQ-DI change from baseline. The odds of achieving ACR50 decreased by 9.2% if disease duration was doubled. The odds of achieving CDAI remission decreased by 15% per 5 additional years of disease duration and decreased by 22% per 10 additional score units of CDAI at baseline.

Conclusion: In this pooled analysis of TCZ-treated RA patients, disease duration explained statistically significant but practically small variations in clinical outcomes. These findings support that TCZ treatment outcomes are not heavily influenced by disease duration or other baseline characteristics.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-disease-duration-and-other-patient-baseline-characteristics-on-outcomes-in-tocilizumab-treated-rheumatoid-arthritis-patients-a-pooled-analysis/