Previous clinical trials have demonstrated that tocilizumab monotherapy was superior to tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to tocilizumab plus methotrexate (MTX). Using the Corrona Rheumatoid Arthritis (RA) registry, the current study sought to assess in routine clinical practice the effectiveness of tocilizumab monotherapy versus TNFi plus varying doses of MTX in patients with RA and prior exposure to TNFi. The Corrona RA registry is an independent, prospective, observational cohort of patients with RA (n = 46,544), recruited from 174 private and academic institutions across the United States.
Eligible patients from the Corrona RA registry were tocilizumab-naïve with RA, had moderate-to-high disease activity, had prior exposure to ≥1 TNFis, initiated tocilizumab monotherapy or TNFi + MTX between 2010 and 2016, and had a 6-month follow-up visit. The primary efficacy outcome was mean change from baseline in Clinical Disease Activity Index (CDAI) at 6 months; secondary outcomes included the proportion of patients who achieved low disease activity (LDA; CDAI ≤10), 20%/50% improvement in modified American College of Rheumatology response criteria (mACR20/mACR50) at 6 months, and mean change from baseline in modified Health Assessment Questionnaire (mHAQ) at 6 months.
Based on MTX dose, patients receiving TNFi + MTX were classified into 4 subgroups (patient numbers are trimmed): ≤10 mg (n = 108), >10 to ≤15 mg (n = 186), >15 to ≤20 mg (n = 273), and >20 mg (n = 107). The propensity score (PS) included age, sex, race, body mass index, smoking status, work status, disease duration, concomitant prednisone use/dose, prior biologic use, ACR functional class and mHAQ, CDAI, and patient pain scores. Sensitivity analysis included stratified-matched populations (stratified by 1 vs ≥2 prior biologics, then matched on PS).
The study population included 301 patients who initiated tocilizumab monotherapy and 772 patients who initiated the TNFi + MTX treatment. Baseline demographics were comparable between the 2 patient cohorts. The study population was predominantly female, with mean age of 54 to 59 years, and mean disease duration of 9.3 to 13.3 years. A few exceptions to note are that a higher proportion of tocilizumab monotherapy initiators had received ≥3 prior biologics, had a significantly longer mean disease duration, and a higher mean baseline CDAI versus those initiating TNFi + MTX.
The analysis showed that patients in all treatment groups had improvement in CDAI scores from baseline at 6 months, with mean change ranging from –6.9 to –9.7. In unadjusted analyses, there were no significant differences in change in CDAI at 6 months between the tocilizumab monotherapy and TNFi + MTX cohorts, except for the MTX >15 mg and >15- to ≤20-mg dose groups. Furthermore, 26.8% to 38% of patients achieved LDA at 6 months; in unadjusted models, there were no significant differences between the tocilizumab monotherapy and TNFi + MTX cohorts in the likelihood of achieving LDA. Adjusted models showed that improvement in CDAI and the likelihood of achieving LDA were similar between the tocilizumab monotherapy group and all TNFi + MTX groups. Similar results were observed in the PS-matched cohorts. In terms of clinical responses, the proportion of patients who achieved mACR20 ranged from 24.3% to 37.6%, and for mACR50, from 13.2% to 20.8%; in unadjusted models, there were no significant differences between the tocilizumab monotherapy and TNFi + MTX cohorts in the likelihood of achieving mACR20 or mACR50 except for the >15- to ≤20-mg dose group.
This real-world study demonstrated that tocilizumab monotherapy was as effective as TNFi + MTX in improving clinical outcomes, including improvements in CDAI, achievement of LDA, achievement of mACR20 and mACR50 responses, and improvement in mHAQ over 6 months in patients with prior TNFi exposure regardless of MTX dose, suggesting that it is an effective treatment option for patients who are intolerant to MTX or prefer not to use it.
Harrold LR, et al. ACR 2017. Abstract 2449.