FRI0169\u2005DOES INITIATING TOCILIZUMAB LEAD TO BETTER DISEASE CONTROL COMPARED TO INITIATING MTX WITH LOW-MODERATE DOSE PREDNISONE IN EARLY RHEUMATOID ARTHRITIS; AN INDIRECT COMPARISON OF U-ACT-EARLY AND CAMERA-II TREAT-TO-TARGET TRIALS

Abstract

Background Treatment with methotrexate (MTX), often with concomitant glucocorticoids, is the cornerstone of early rheumatoid arthritis (RA) therapy. However, it may be less effective compared to (expensive) biological disease modifying anti-rheumatic drugs, such as tocilizumab (TCZ). Hitherto, the effectiveness and safety of MTX in combination with glucocorticoids have never been compared to TCZ with or without MTX. Objectives To compare effectiveness and safety of initiating TCZ, or TCZ with MTX (TCZ+MTX) to initiation of MTX with 10mg prednisone (MTX+Pred) all in a step-up treat-to-target treatment strategy in early RA patients. Methods Individual patient data of the U-Act-Early (n= 317) and CAMERA-II (n= 236) trials were used. Both were 2-year, double-blind, randomised, placebo-controlled studies evaluating step-up tight-control, treat-to-target treatment strategies with the opportunity to taper, in case of sustained remission, TCZ and/or MTX.1,2 Using MTX (n=108+ 119) as the reference strategy, TCZ+MTX (n= 106) and TCZ (n= 103) were compared with MTX+Pred (n= 117): primary outcome was the disease activity score (DAS28) over time. Secondary outcomes were remission, defined as DAS28<2.6, and the ConRew score (cumulative occurrence of remission and sustainment of remission). To assess the influence of acute phase reactants (APRs) on the results a disease activity outcome without APRs was also analysed (i.e. CDAI, modified due to lack of VAS physician in CAMERA-II). Multiple imputation was used for missing baseline data: HAQ, rheumatoid factor (RF) and smoking status. Multi-level models were used to account for clustering of patients within trials and for repeated measurements within patients over time. All models were corrected for baseline DAS28, HAQ, RF-status and smoking using fixed (and random) effects. Results Differences between U-Act-Early and CAMERA-II for RF seropositivity and DAS28 at baseline were observed; respectively 73% vs. 60% (p<0.01) and 5.2 vs. 5.7 (p=0.01). DAS28 was statistically significantly lower over time for TCZ+MTX compared to MTX+Pred (mean difference: -0.62 [95%CI -1.14 to -0.10]), but not for TCZ, Table 1. Remission occurred more often in TCZ+MTX and TCZ compared to MTX+Pred: relative risk 1.11 [95%CI 1.02 to 1.22] and 1.09 [1.00 to 1.20], respectively. ConRew scores were in line but not statistical significant different, Table 1. When using modified-CDAI, TCZ strategies did not show better control of disease activity over time than MTX+Pred (mean difference in log transformed values: TCZ+MTX vs. MTX+Pred: 0.10 [95%CI -0.16 to 0.36]; TCZ vs. MTX+Pred: 0.24 [95%CI -0.04 to 0.52]), Table 1. No differences in safety outcomes could be established, Table 2. Conclusion In early RA patients, TCZ-based strategies resulted in better DAS28 over time compared to MTX+Pred, as well as higher percentage of remission, part of these effects may be due to a specific effect of TCZ on APRs. References [1] Bijlsma JWJ, et al. Lancet. 2016;388:343-55. [2] Bakker MF, et al. Ann Intern Med. 2012;156:329-339. Disclosure of Interests Maxime Verhoeven: None declared, Janneke Tekstra: None declared, Jacob M. van Laar Grant/research support from: Genentech, Consultant for: F. Hoffmann-La Roche, Johannes WJ Bijlsma Grant/research support from: The department of the author who included patients (JWJB) in the U-Act-Early trial received reimbursements from Roche Nederland BV. JWJB reported grants and fees from Roche, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and UCB University Medical Center Utrecht, Utrecht University, Consultant for: SUN Pharma, Speakers bureau: Lilly, Roche, Attila Pethoe-Schramm Shareholder of: F. Hoffmann-La Roche, Employee of: F. Hoffmann-La Roche, Michelle Borm Employee of: An employee of Roche Nederland BV, Floris Lafeber Shareholder of: ArthroSave, Grant/research support from: FOREUM; Dutch Arthritis Society, Paco Welsing: None declared