Dose Escalation and Co-therapy Intensification Between Etanercept, Adalimumab, and Infliximab: The CADURA Study

Carter Thorne1, Gilles Boire2, Andrew Chow3, Kirsten Garces4, Fang Liu5, Melanie Poulin-Costello4, Valery Walker5, *, Boulos Haraoui6
1 The Arthritis Program Research Group, Southlake Regional Health Centre, c/o 43 Lundy’s Lane, Newmarket, ON, L3Y 3R7, Canada
2 Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de l’Estrie-CHUS), Université de Sherbrooke, Sherbrooke, QC, Canada
3 Credit Valley Rheumatology, Mississauga, ON, Canada
4 Amgen Canada Inc., Mississauga, ON, Canada
5 Optum, 5500 North Service Road, Suite 501, Burlington, ON, L7L 6W6, Canada
6 Institut de Rhumatologie de Montreal, Montreal, QC, Canada

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© 2017 Thorne et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Health Economics and Outcomes Research, Optum, 5500 North Service Road, Suite 501, Burlington, ON, L7L 6W6, Canada; Tel: 289-313-6030; E-mail:



To compare anti-TNF dose escalation, DMARD and/or glucocorticoid intensification, switches to another biologic, and drug and drug-related costs over 12 and 18 months for rheumatoid arthritis (RA) patients initiating etanercept (ETN), adalimumab (ADA), or infliximab (IFX) in routine clinical practice across Canada.


A retrospective chart review of biologic-naïve adult RA patients newly initiating ADA, ETN, or IFX between January 01, 2006 and December 31, 2012 from 11 practices across Canada.


There were 314 patients in the 12-month analysis and 217 in the 18-month analysis. No dose escalation occurred with ETN over 12 and 18 months versus 38% and 32% for IFX (p<0.001) and 2% and 2% for ADA (p=0.199, p=0.218). Over 18 months, dose escalation and/or DMARD and/or glucocorticoid intensification was less frequent among ETN (16%) versus IFX (44%, p=0.005) and ADA (34%, p=0.004). By 18 months, 22% of patients initiating ADA had switched to another biologic compared with 6% of ETN patients (p=0.001).

Patients initiating ETN had lower total (drug and drug-related) costs over 12 and 18 months compared to IFX, and no difference compared to ADA when adjusted for potential confounders. Patients with dose escalation had higher costs compared to those with no dose escalation.


Physicians were more likely to escalate the dose of IFX, but optimize co-therapy with ADA and ETN. ETN patients had no dose escalation and were less likely to have DMARD and/or glucocorticoid intensification than ADA patients. ETN-treated patients had lower costs compared to IFX patients.

Keywords: Rheumatoid arthritis, Etanercept, Adalimumab, Infliximab, Dose escalation, Intensification.