Session Information
Date: Tuesday, November 10, 2015
Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: A delay in effective treatment is known to negatively affect long term treatment outcomes in patients (pts) with rheumatoid arthritis (RA). The purpose of this study was to compare the effects of disease duration and the number of prior failed disease modifying anti-rheumatic drugs (DMARDs) before effective treatment, on the achievement of long term outcomes in pts with early or established RA.
Methods: Data from two randomized controlled trials, PREMIER and DE019, were used. In PREMIER, pts with mean RA duration < 1 year (yr), who were TNF inhibitor-(TNFi) and MTX-naïve received adalimumab (ADA), methotrexate (MTX), or ADA+MTX. In DE019, TNFi-naïve pts with mean RA duration 11 yrs, and an insufficient response to MTX received 20 mg/40mg ADA every other week +MTX, or PBO+MTX. The association of either variable (prior disease duration or prior DMARDs) with the endpoints was modeled while controlling for the other variable using linear or logistic regression. RA duration and number of prior DMARDs were grouped and the groups were treated as ordinal variables. For PREMIER, RA duration groups were ≤1yr, >1 to ≤2yr and >2yr and for prior DMARDs, groups were: 0 or ≥1 DMARD. For DE019, RA duration groups were: ≤1yr, >1 to ≤5yr and >5 to ≤10 yr, and >10yr, and for prior DMARDs groups were: MTX+0 or 1 DMARD, MTX + 2 DMARDs and MTX +>2 DMARDs. The effect of RA duration/ exposure to prior DMARDs was determined for the following endpoints: week (wk) 52 ACR 20/50/70 response rates, mean DAS28 / SDAI / CDAI and HAQ; and mean changes from baseline (BL) to wk 52 in DAS28 / SDAI / CDAI/ HAQ (for changes from BL, a positive regression coefficient indicates a smaller change) .
Results: In PREMIER, in the ADA+MTX arm (268 pts), longer RA duration led to a smaller change from BL to wk 52 in CDAI and SDAI (2.95 and 3.59 respectively; p<0.05); higher absolute DAS28, CDAI and SDAI scores, and lower ACR response rates at wk 52. In DE019, for pts receiving ADA 40 mg +MTX (207 pts), an exposure to a larger number of prior DMARDs was significantly associated (p<0.05) with increased (by 0.21) DAS28 scores at wk 52, and a smaller (by 0.15) change in HAQ scores from BL to wk 52 (p<0.01). Longer RA duration was significantly associated (p<0.05) with an increase of 0.13 in wk 52 HAQ scores. Larger number of prior DMARDs or longer RA duration were associated, although not significantly, with lower ACR response rates at week 52.
Conclusion: In early RA, disease duration but not number of prior DMARDs, was significantly associated with a smaller change from BL to wk 52 in SDAI and CDAI, higher CDAI and SDAI scores and lower ACR response rates at wk 52.
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Table: Association of wk 52 outcomes with number of prior DMARDs or disease duration. Regression coefficient estimate (95% CI) |
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PREMIER |
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Wk 52 outcome |
# prior DMARDs |
Disease duration |
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|
|
ADA+MTX |
MTX |
ADA+MTX |
MTX |
|
ACR20 |
-0.37 (-1.25, 0.50) |
-0.05 (-1.05, 0.95) |
-0.22 (-0.78, 0.35) |
0.50 (-0.23, 1.23) |
|
ACR50 |
-0.49 (-1.18, 0.21) |
0.39 (-0.34, 1.13) |
-0.05 (-0.52, 0.42) |
-0.12 (-0.57, 0.33) |
|
ACR70 |
-0.60 (-1.22, 0.02) |
0.26 (-0.44, 0.97) |
-0.03 (-0.45, 0.39) |
0.05 (-0.39, 0.49) |
|
DAS28 |
0.07 (-0.29, 0.44) |
0.10 (-0.37, 0.57) |
0.10 (-0.14, 0.35) |
-0.17 (-0.46, 0.12) |
|
CDAI |
-0.30 (-3.44, 2.84) |
0.05 (-4.51, 4.61) |
1.75 (-0.40, -3.90) |
-1.44 (-4.23, 1.35) |
|
SDAI |
-0.78 (-4.16, 2.6) |
0.17 (-4.64, 4.99) |
1.87 (-0.43, 4.17) |
-1.55 (-4.52, 1.42) |
|
ΔDAS |
-0.02 (-0.42, 0.39) |
0.14 (-0.36, 0.63) |
0.19 (-0.08, 0.47) |
-0.11 (-0.41,0.20) |
|
ΔCDAI |
0.12 (-4.16, 4.41) |
1.83 (-3.32, 6.97) |
2.95* (0.00, 5.90) |
-0.45 (-3.60, 2.71) |
|
ΔSDAI |
-0.91 (-5.80, 3.98) |
2.0 (-2.81, 7.81) |
3.59* (0.26, 6.93) |
-0.33 (-3.91, 3.25) |
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DE019 (ADA 40mg + MTX) |
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|
# prior DMARDs |
Disease duration |
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ACR20 |
-0.06 (-0.44, 0.32) |
-0.02 (-0.35, 0.31) |
|
ACR50 |
-0.21 (-0.57, 0.15) |
-0.15 (-0.46, 0.16) |
|
ACR70 |
-0.31 (-0.72, 0.09) |
-0.13 (-0.47, 0.22) |
|
DAS28 |
0.21* (0.00, 0.43) |
-0.01 (-0.19, 0.17) |
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SDAI |
2.00 (-0.01, 4.00) |
-0.09 (-1.78, 1.60) |
|
HAQ |
0.08 (-0.05, 0.21) |
0.13* (0.02, 0.24) |
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ΔDAS |
0.21 (-0.01, 0.42) |
0.00 (-0.18, 0.19) |
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ΔSDAI |
1.73 (-0.87, 4.32) |
-0.09 (-2.28, 2.10) |
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ΔHAQ |
0.15* (0.04, 0.25) |
0.03 (-0.06, 0.12) |
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*p<0.05; Δ, change |
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To cite this abstract in AMA style:
Smolen JS, Aletaha D, Chen S, Florentinus S. The Effect of Prior Disease Duration and Prior DMARD Use on Treatment Outcomes in Patients with Early or Established Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-effect-of-prior-disease-duration-and-prior-dmard-use-on-treatment-outcomes-in-patients-with-early-or-established-rheumatoid-arthritis/. Accessed March 23, 2023.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-prior-disease-duration-and-prior-dmard-use-on-treatment-outcomes-in-patients-with-early-or-established-rheumatoid-arthritis/