Among biologic-naïve patients with rheumatoid arthritis (RA), disease duration had a statistically significant but clinically small effect on tocilizumab treatment outcomes, according to study results published in Rheumatology. However, the number of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) used, disability and disease activity were significantly associated with treatment outcomes.
Previous studies suggested that disease duration is a predictor of response to treatment for RA, as early treatment initiation was associated with better outcomes. The current study aimed at exploring the impact of disease duration, alone or in combination with other baseline factors, on response to treatment with tocilizumab.
Using data pooled from all 12 phase 3 and phase 4 clinical studies conducted by the sponsor, researchers identified patients with RA who initiated tocilizumab treatment and collected information on demographics and patients characteristics, as well as baseline disease and therapy characteristics.
Response to tocilizumab treatment was assessed as change from baseline to 24 weeks in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores and as the proportions of patients with ≥50% improvement in American College of Rheumatology criteria and CDAI remission (CDAI ≤ 2.8).
The study sample included 5462 (mean age 53.3 years, 80.9% women) patients treated with tocilizumab. Most patients had RA for more than 2 years, including 1274 patient with RA duration between 2 and 5 years, 1173 patients with disease duration between 5 and 10 years, and 1692 subjects with RA for more than 10 years. Patients with longer disease duration were older and had been exposed to more csDMARDs than patients with shorter disease duration.
At 24 weeks, treatment with tocilizumab was associated with improvements in all outcomes investigated. While disease duration had a statistically significant negative effect on outcomes with tocilizumab treatment, it accounted for <2% of the variation in changes of HAQ-DI and CDAI. Each additional 5 years duration of RA was associated with 15% (odds ratio, 0.85; 95% CI, 0.79-0.91) decreased odds of achieving CDAI remission.
Baseline values of HAQ-DI and CDAI had a more significant impact on the outcomes at week 24, accounting for 32% and 15% of variations in changes of these measures, respectively. These findings suggest that greater disability and higher disease activity at baseline may be better predictors of response to tocilizumab treatment. The odds of achieving CDAI remission at week 24 decreased by 22% (odds ratio, 0.78; 95% CI, 0.71-0.86) for each additional 10 units of baseline CDAI.
Doubling the duration of RA decreased the odds of achieving ACR50 response at week 24 by 9.2% (odds ratio, 0.91; 95% CI, 0.87-0.95).
The study had several limitations, including heterogeneous patient population, exclusion of csDMARD-naïve patients, and missing data.
“[T]ocilizumab treatment outcomes from clinical trials were not heavily influenced by disease duration, either alone or in combination with other baseline characteristics, in patients with established RA. Rather, baseline values of outcome variables were stronger predictors of outcome variables,” concluded the researchers.
Disclosure: This clinical trial was supported by F. Hoffmann-La Roche Ltd. Please see the original reference for a full list of authors’ disclosures.
Rubbert-Roth A, Aletaha D, Devenport J, et al. Effect of disease duration and other characteristics on efficacy outcomes in clinical trials of tocilizumab for rheumatoid arthritis. Rheumatology (Oxford). Published online Aug 26, 2020. doi:10.1093/rheumatology/keaa259