Clinical Remission and/or Minimal Disease
Activity in Patients Receiving Adalimumab
Treatment in a Multinational, Open-Label,
Twelve-Week Study
GERD R. BURMESTER,
1
GIANFRANCO FERRACCIOLI,
2
RENE
´
-MARC FLIPO,
3
INDALECIO MONTEAGUDO-SA
´
EZ,
4
KRISTINA UNNEBRINK,
5
SONJA KARY,
5
AND HARTMUT KUPPER
5
Objective. To evaluate the effect of adalimumab treatment on clinical remission and/or minimal disease activity (MDA)
in 6,610 patients with active rheumatoid arthritis (RA) who were enrolled in the Research in Active RA trial, a
multinational, open-label, 12-week study with an optional extension period.
Methods. Clinical remission was defined as a Disease Activity Score in 28 joints (DAS28) <2.6, Simplified Disease
Activity Index (SDAI) score <3.3, or Clinical Disease Activity Index (CDAI) score <2.8. MDA required absence of tender
and swollen joints plus erythrocyte sedimentation rate (ESR) <10 mm/hour; DAS28 score <2.85; or achievement of 5 of
7 core criteria for pain, swollen/tender joints, physical function, physician/patient global assessment, and ESR. Time to
and time in remission/MDA and response predictors were analyzed using Kaplan-Meier estimates and Cox proportional
hazards regression analysis, respectively.
Results. A total of 38%, 24%, and 27% of patients achieved remission defined as DAS28 <2.6, SDAI <3.3, and CDAI <2.8,
respectively. MDA was observed in 45% of patients by DAS28 <2.85, in 43% by the core set of criteria, and in 13% by
absence of tender/swollen joints plus ESR <10 mm/hour. Median times in continuous remission and MDA were 3.4 and
4.4 months, respectively. Predictors for remission (DAS28 <2.6) and MDA (DAS28 <2.85) were male sex; younger age;
concomitant disease-modifying antirheumatic drug use; lower baseline DAS28, CRP concentration, and Health Assess-
ment Questionnaire disease index score; <1 comorbidity; and tumor necrosis factor antagonist naivety.
Conclusion. During adalimumab treatment, 25% of patients experienced clinical remission and nearly half achieved
MDA. To our knowledge, this analysis represents the largest prospective clinical trial data set to be assessed using
Outcome Measures in Rheumatology Clinical Trials MDA criteria.
INTRODUCTION
Since the introduction of biologic response modifiers that
inhibit tumor necrosis factor (TNF), the expectations of
medical treatment for active rheumatoid arthritis (RA)
have changed markedly. Several clinical trials have dem-
onstrated the efficacy of TNF antagonists (adalimumab,
etanercept, and infliximab) in significantly reducing dis-
ease activity and limiting progression of joint destruction
and subsequent disability in patients with RA (1– 4). Ap-
propriate management of RA requires more than the as-
sessment of relative improvement or change in signs and
symptoms. Being able to assess the actual state of disease
ClinicalTrials.gov identifier: NCT00448383.
Supported by a grant from Abbott GmbH & Co. KG, Lud-
wigshafen, Germany. Dr. Burmester’s work was supported
by Abbott, Schering-Plough, Wyeth, and Roche.
1
Gerd R. Burmester, MD: Charite ´ University Medicine
Berlin, Berlin, Germany;
2
Gianfranco Ferraccioli, MD:
Catholic University of Rome, Rome, Italy;
3
Rene ´-Marc
Flipo, MD: University Hospital, Lille, France;
4
Indalecio
Monteagudo-Sa ´ ez, MD: Hospital General Universitario Gre-
gorio Maran ˜o ´ n, Madrid, Spain;
5
Kristina Unnebrink, PhD,
Sonja Kary, MD, MA, Hartmut Kupper, MD: Abbott GmbH &
Co. KG, Ludwigshafen, Germany.
Dr. Burmester has received consultant fees, speaking
fees, and honoraria (more than $10,000 each) from Abbott,
Schering-Plough, Wyeth, and Roche. Dr. Ferraccioli has re-
ceived consultancy fees and speaking fees (less than $10,000
each) from Abbott, Wyeth, and Schering-Plough. Dr. Unne-
brink holds stock options in Abbott. Dr. Kary is a contractor
for Abbott (Germany). Dr. Kupper holds stock options in
Abbott.
Address correspondence to Gerd R. Burmester, MD, De-
partment of Rheumatology and Clinical Immunology,
Charite ´ University Medicine Berlin, Charite ´platz 1, 10117
Berlin, Germany. E-mail: gerd.burmester@charite.de.
Submitted for publication March 19, 2007; accepted in
revised form June 15, 2007.
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 59, No. 1, January 15, 2008, pp 32– 41
DOI 10.1002/art.23247
© 2008, American College of Rheumatology
ORIGINAL ARTICLE
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