Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Clinical and Radiographic Implications of Time to Treatment Response in Patients with Early Rheumatoid Arthritis.

Keystone7,  Ed C., Weinblatt4,  Michael E., Haraoui5,  Boulos, Guerette2,  Benoit, Mozaffarian1,  Neelufar, Patra3,  Kaushik, Kavanaugh6,  Arthur

Abbott Laboratories, Abbott Park, IL
Abbott Laboratories, France
Abbott Laboratories
Brigham & Womens Hospital, Boston, MA
Institut de Rhumatologie, Montreal, QC, Canada
University of California-San Diego, La Jolla, CA
University of Toronto, Toronto, ON, Canada

Background:

For patients with rheumatoid arthritis (RA), there has been increased interest in treating to target early and quickly. While some advocate treatment adjustment at 12 weeks (wks), data support the possibility of later responses to therapy. The longer-term radiographic implications of such a delay in response have not been examined previously.

Objective:

To evaluate the association of early (12 wks) and delayed (24 wks) clinical responses with rates of clinical remission, low-disease activity (LDAS), and rapid radiographic progression (RRP) at 52 wks in patients with early RA treated with methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX combination therapy in the PREMIER trial.

Methods:

PREMIER was a 104-wk, phase III, randomized, placebo-controlled trial in MTX-naïve patients with early RA, who were randomized 1:1:1 to one of three treatment groups: MTX, ADA 40 mg every other wk (eow), or ADA 40 mg eow + MTX. In this post hoc analysis, observed data comparing MTX with ADA + MTX therapy are presented. Clinical outcome measures included the 28-joint Disease Activity Score (DAS28) and mean change from baseline in modified Total Sharp Score (DmTSS) at 52 wks. Patients were categorized on the basis of clinical response (DAS28 improvement >=1.2 or 20/50/70% improvement in ACR score) at 12 and 24 wks as responders or non-responders: "early responders" achieved the clinical target at wk 12 and maintained the response at wk 24; "delayed responders" did not meet the clinical target until wk 24. The percentages of patients at 52 wks with LDAS (DAS28 <3.2), clinical remission (DAS28 <2.6), and RRP (DmTSS >3 units/year) in each group were determined.

Results:

In both treatment groups, early clinical responses were associated with better long-term outcomes than delayed responses (Table). Achieving early or delayed ACR70 responses did not result in treatment group differences in the proportion of patients achieving LDAS or clinical remission at wk 52. Importantly, delayed responses to MTX resulted in a high proportion of patients with RRP. Indeed, delayed ACR70 responses were associated with an RRP prevalence of 40%. In addition, an early improvement in DAS28 >=1.2 with MTX was insufficient to slow radiographic progression (41% RRP). In contrast, early or delayed clinical responses to ADA + MTX resulted in low proportions of RRP at 52 wks, even for patients with a delayed ACR20 response (11% RRP). Of note, ADA + MTX-treated delayed responders had less RRP than MTX-treated early responders.

Table. Association of Treatment and Time to Clinical Reponse With Long-term Outcome

TreatmentResponder TypeResponse at Week 12stResponse at Week 24st% DAS28 <3.2 (LDAS)% DAS28 <2.6 (Remission)%DmTSS < Uiyr (RRP)
MTXEarlyACR70RACR70R948918
MTXDelayedACR70NRACR70R704740
ADA-MTXEarlyACR70RACR70R98855
ADA-MTXDelayedACR70NRACR70R824113**
MTXEarlyDDAS28>=1.2DDAS28>=513241
MTXDelayedDDAS28<=1.2DDAS28>=241053
ADA-MTXEarlyDDAS28>=1.2DDAS28>=67**46*11*
ADA-MTXDelayedDDAS28<=1.2DDAS28>=45255**
*P <0.05;**P <0.01;***P <0.001 for between treatment group companies of MTX and ADA + MTX#DDAS28 are improvements, values are considered less than prior assessment; R = Responder; NR = Non-responder

Conclusions:

MTX-treated patients with early RA who fail to achieve high-level response (e.g. ACR70) within 12 wks are at risk for RRP and should be considered for treatment adjustment. ADA + MTX treatment is associated with better clinical outcomes and less severe radiographic progression at 52 wks, even among patients with a delayed clinical response.

To cite this abstract, please use the following information:
Keystone, Ed C., Weinblatt, Michael E., Haraoui, Boulos, Guerette, Benoit, Mozaffarian, Neelufar, Patra, Kaushik, et al; Clinical and Radiographic Implications of Time to Treatment Response in Patients with Early Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1102
DOI: 10.1002/art.28869

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