Background Tocilizumab (TCZ), a humanized interleukin-6 receptor inhibitor, has been shown effective in suppressing symptoms of rheumatoid arthritis (RA). In U-Act-Early, a significantly greater proportion of patients with early RA who initiated TCZ (84%) or TCZ plus MTX therapy (86%) achieved sustained remission (Disease Activity Score assessing 28 joints (DAS28) <2.6 with ≤4 swollen joints for ≥24 weeks), when compared to those initiating MTX (44%).
Objectives To determine the effect of treat-to-target TCZ therapy, with or without MTX, on health-related quality of life (HRQoL) in disease modifying anti-rheumatic drugs (DMARD)-naïve patients with early RA.
Methods Patients (n=317) were randomized to initiate TZC, TCZ+MTX or MTX therapy and treated according to a step-up strategy. TCZ was given (8 mg/kg) every 4 weeks and MTX (oral) was started at 10 mg/week and increased with steps of 5 mg steps 4 weekly up to 30 mg/week (or maximum tolerable dose) until remission. If after 20 weeks remission was not achieved, hydroxychloroquine was added and discontinued 12 weeks thereafter if the target still was not achieved. Patients who originally initiated monotherapy then switched to TCZ+MTX therapy and those already on this combination therapy switched to a tumour necrosis factor inhibitor. To evaluate the effect of TCZ on HRQoL, we used the 36-item Short-Form (SF-36), which can be summarized into a physical (PCS) and mental (MCS) component score. HRQoL was measured at baseline and after 12, 24, 52, and 104 weeks. A linear mixed effect model with a random intercept was used to evaluate differences between treatment strategies over time with visit (time), strategy, baseline SF-36 score, baseline DAS28 level (i.e., DAS28 <5.1 or ≥5.1) and centre as fixed effects. The proportions of patients exceeding the minimum clinically important differences (MCID, ≥2.5-point increase from baseline) were tested for significance using the two-sided Pearson's chi-squared test.
Results We found significantly greater improvements over time in the SF-36 PCS in patients initiating treatment with TCZ (TCZ vs MTX; p=0.041, TCZ+MTX vs MTX; p=0.011, Fig. 1). For the SF-36 MCS, no significant differences over time were noted between the treatment arms (p≥0.11). A significantly higher proportion of patients initiating treatment with TCZ (76%; p=0.016, 89%; p=0.030) or TCZ+MTX (73%; p=0.049, 89%; p=0.027) achieved MCID in the SF-36 PCS at week 12 and week 52, when compared to those initiating treatment with MTX (59% and 73%, respectively). Although the proportions of patients achieving MCID in the SF-36 MCS were numerically higher in the TCZ arms, no significant differences were found (p≥0.06).
Conclusions Initiation of TCZ, with or without MTX, at start of therapy resulted in statistically significant and clinically relevant improvements in the HRQoL when compared to initiation of MTX alone and may be considered as a valuable treatment strategy in DMARD-naïve patients with early RA.
Bijlsma JW, Welsing PM, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet 2016; 388:343–55.
Disclosure of Interest X. Teitsma: None declared, J. Jacobs: None declared, P. Welsing: None declared, A. Pethö-Schramm Employee of: Employee of F.Hoffmann-La Roche, M. Borm Employee of: Roche Nederland B.V., J. van Laar Consultant for: Received fees from MSD, Pfizer, Roche, Eli Lilly and BMS, F. Lafeber: None declared, J. Bijlsma Grant/research support from: Received research grants (to his department) and consultancy fees from AbbVie, BMS, Crescendo, MSD, Mundipharma, Pfizer, Roche, Sun and UCB