Background The U-ACT EARLY study is a 2-year, randomized placebo-controlled, double blind study in which disease modifying antirheumatic disease (DMARD)-naive early RA patients were randomized to initiate tocilizumab (TCZ, n=103), methotrexate (MTX, n=108)) or their combination (n=106), and treated according to a step-up strategy. The primary endpoint, sustained remission (SR, defined as DAS28 <2.6 and <4 swollen joints for >24 weeks), was achieved by significantly more patients in the TCZ+MTX (86%) and TCZ (84%) groups, compared to MTX (44%). Here we report a post hoc analysis of sustained drug free remission (sDFR).
Objectives To compare the number of patients achieving sDFR between the three treatment strategies.
Methods We analyzed data of all 317 patients included in the study. TCZ was given intravenously (8 mg/kg 4 weekly) and MTX was increased over 3 months from 10 to 30 mg/week (or maximum tolerated dose) until remission. If remission was not reached after 20 weeks, hydroxychloroquine was added. Twelve weeks thereafter, if the target was not achieved, the placebo was substituted by TCZ/MTX. If SR was achieved, medication was tapered stepwise and stopped provided remission persisted. Differences in prevalence, time-to, and duration of sDFR (drug-free for >3 months with remission) were analyzed. To identify predictive factors for achieving sDFR, baseline data were analyzed using a backward selection procedure (p≤0.10).
Results Table 1 shows baseline characteristics. The proportion of patients achieving sDFR was significantly higher in the TCZ+MTX (35%, p<0.01) and TCZ (27% p<0.01) strategy, compared to MTX (11%, Fig. 1). In patients achieving it, the median time (IQR) to achieve sDFR was shorter in the TCZ+MTX (48 (44–56) weeks; p=0.09) and TCZ strategy (52 (44–67) weeks; p=0.18) when compared to MTX (60 (52–76) weeks). The median duration (IQR) of sDFR within the study period was 44 (16–56), 32 (20–48) and 28 (20–44) weeks (p=0.15) in the TCZ+MTX, TCZ and MTX group, respectively. Baseline HAQ (OR 0.2 (95% CI: 0.1–0.4), any (RF and/or anti-CCP) seropositivity (OR 0.5 (95% CI: 0.2–0.8) and initiation with TCZ+MTX (OR 3.9 (95% CI: 1.9–8.3) or TCZ (OR 3.4 (95% CI: 1.5–7.3) were significant predictors for achieving sDFR. The Area Under the Curve (AUC-ROC) of the multivariable model was 0.73 (95% CI: 0.67–0.80), indicating fair discriminative ability. In our sample, a classifier with 84% sensitivity and 53% specificity correctly predicted achievement of sDFR in 66% of patients.
Conclusions Early RA patients initiating tight-control TCZ treatment achieve sDFR more often and earlier, compared to MTX. Predictors of sDFR include TCZ treatment itself, as well as baseline HAQ and being seronegative.
Disclosure of Interest X. Teitsma: None declared, J. Jacobs: None declared, P. Welsing: None declared, T. Woodworth Employee of: Roche, A. Pethö-Schramm Employee of: Roche, M. Borm Employee of: Roche, C. Bernasconi Employee of: Roche, F. Lafeber: None declared, J. Bijlsma Grant/research support from: received research grants (to his department) from AbbVie, BMS, Crescendo, MSD, Mundipharma, Pfizer, Roche, Sun, UCB./, Consultant for: received consultancy fees from AbbVie, BMS, Crescendo, MSD, Mundipharma, Pfizer, Roche, Sun, UCB.