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 Functional Improvements in Early RA Following Treatment with Adalimumab Plus Methotrexate Compared with Methotrexate Monotherapy: 26-Week Results of the OPTIMA Trial.

Kavanaugh5,  Arthur, Fleischmann6,  Roy, Emery3,  Paul, Guerette1,  Benoit, Redden2,  Laura, Patra2,  Kaushik, Smolen4,  Josef S.

Abbott Laboratories, Rungis, France
Abbott Laboratories, Abbott Park, IL
Leeds Teaching Hospital, Leeds, United Kingdom
Medical University of Vienna and Hietzing Hospital, Vienna, Austria
University of California San Diego, La Jolla, CA
University of Texas Southwestern Medical Center, Dallas, TX

Background:

The optimal treatment approach to achieve and sustain low disease activity (LDA) with TNF antagonists and methotrexate (MTX) in patients with early rheumatoid arthritis (RA) has not been resolved.

Methods:

OPTIMA is an ongoing Phase 4, randomized, double-blind trial to determine the Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (ADA) in MTX-naive patients with early RA. Subjects with RA <1 year, DAS28 >3.2, >=6 SJC, >=8 TJC, ESR >=28 mm/h or CRP >=1.5 mg/dL, and >=1 of: >1 erosions or RF+ or anti-CCP+ were randomized 1:1 to ADA (40 mg eow) +MTX (titrated to 20 mg/wk by week 8) or placebo (PBO) +MTX for the first 26 weeks. ADA+MTX subjects achieving LDA (DAS28 <3.2) at weeks 22 & 26 were re-randomized to compare continued combination therapy versus ADA withdrawal for the 52-week Period 2; PBO+MTX subjects with LDA at weeks 22 & 26 remained blinded on MTX monotherapy. Any subject failing to meet LDA at week 22 and/or 26 was given open-label ADA+MTX. A high-field 1.5T MRI substudy was conducted on the metacarpophalangeal and wrist joints at baseline, week 26, and week 78.

Results:

OPTIMA enrolled 1,032 subjects (PBO+MTX N=517, ADA+MTX N=515); a similar percentage of subjects discontinued prematurely in each treatment group (table). Baseline characteristics were comparable between groups: 74% female, 89% white, mean RA duration of 4.2 months, mean DAS28 of 6.0 with 81% having DAS28 >=5.1, mean SDAI of 43.6, mean CDAI of 40.8, mean SJC66 of 18.1, mean CRP of 2.9 mg/dL, and mean HAQ disability index (HAQ-DI) score of 1.6. Subjects treated with ADA+MTX demonstrated a significantly more rapid response, with a greater proportion achieving clinical and functional improvements through 26 weeks compared with PBO+MTX subjects (table).

Table. Subjects' Disposition and Clinical Outcomes through 26 weeks of OPTIMA*

Subjects, n (%)RandomizedCompleted Period 1
PBO+MTX 517  460 (89%) 
ADA+MTX 515  466 (91%) 
 Week 2Week 12Week 26
 PBO+MTXADA+MTXPBO+MTXADA+MTXPBO+MTXADA+MTX
ACR 20/50/70, % pts16/2/046/18/558/30/1173/49/3057/34/1770/52/35
DAS28 <3.2, % pts41522422647
DAS28 <2.6, % pts1710261634
SDAI <=3.3, % pts0.425141020
CDAI <=2.8, % pts0.237131120
SJ (0–66), mean (SD)‡14119785
CRP (mg/dL), mean (SD)‡2.511.40.91.30.8
HAQ <=0.5, % pts102530413345
*Results based on nonresponder imputation analysis unless otherwise noted; P <0.001 for all between-groups comparisons;
‡LOCF.

In the MRI sub-study, PBO+MTX (N=32) and ADA+MTX (N=27) subjects, respectively, had mean changes from baseline to week 26 in synovitis of -2.0 and -3.6 (P=0.003), in erosion of 1.4 and -0.8 (P=0.004), and in osteitis of 0.0 and -4.0 (P=0.006), suggesting more improvement of joint inflammation and damage in the ADA+MTX group. Serious adverse events occurred in 31 (6%) PBO+MTX and 36 (7%) ADA+MTX subjects. Serious infections occurred in 6 (1.2%) and 13 (2.5%) subjects in the PBO+MTX and ADA+MTX groups, respectively. There was 1 case of peritoneal TB in the ADA+MTX group, and opportunistic infections excluding TB occurred in 3 (0.6%) PBO+MTX and 1 (0.2%) ADA+MTX subjects. There were no cases of lymphoma or demyelinating disease. Six deaths occurred in the ADA+MTX group, 5 related to infection and 4 in subjects >=65 years, compared with 1 death in the PBO+MTX group.

Conclusion:

Treatment of early RA with ADA+MTX resulted in rapid, enhanced clinical and functional responses and improved MRI profiles, compared with MTX monotherapy through 26 weeks.

To cite this abstract, please use the following information:
Kavanaugh, Arthur, Fleischmann, Roy, Emery, Paul, Guerette, Benoit, Redden, Laura, Patra, Kaushik, et al; Clinical and Functional Improvements in Early RA Following Treatment with Adalimumab Plus Methotrexate Compared with Methotrexate Monotherapy: 26-Week Results of the OPTIMA Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1791
DOI: 10.1002/art.29556

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