Background/Purpose: In early rheumatoid arthritis (RA), achievement of clinical remission and low disease activity (LDA) limits joint damage and disability.¹ Anti-TNF agents are effective in rapidly inducing remission in early RA, which may improve the likelihood of long-term treatment success.² According to current EULAR guidelines, biologic withdrawal should be considered after a good clinical state is achieved,¹ but little is yet known about which patients are the best candidates for treatment reduction or withdrawal. In the PRIZE study, the impact of demographic and disease characteristics and early treatment response on the achievement of sustained remission was assessed in patients with early RA. 

Methods: Methotrexate (MTX)-/biologic-naïve patients with early moderate-severe RA who achieved DAS28 ≤3.2 at week 39 and <2.6 at week 52 after open-label treatment with etanercept (ETN) 50 mg+MTX 10-25 mg (Phase 1 [P1]) were randomized to ETN 25 mg+MTX, MTX alone, or placebo (PBO) for 39 weeks in the double-blind phase (Phase 2 [P2]). With Mantel-Haenszel chi-square tests, the association between baseline (BL) characteristics and P1 treatment responses and achievement of P2 sustained remission (ie, DAS28 <2.6 at week 76 and 91, without corticosteroids for week 52-64) was analyzed. BL demographic and disease characteristics will also be analyzed in patients who achieved early P1 remission (ie, first DAS28 remission on day 0-178) vs late P1 remission (ie, first DAS28 remission after day 178). 

Results: Predictors of P2 sustained remission in the ETN 25 mg+MTX group included: achievement of DAS28 sustained remission over weeks 13-52 (vs patients without this P1 response: 79% vs 54%; P=0.044); DAS28 LDA over weeks 13-52 (76% vs 41%; P=0.007); and ACR/EULAR Boolean remission at week 52 (71% vs 44%; P=0.049). Rapid and robust responses in P1 (ie, first DAS28 remission in days 0-179, mean DAS28 ≤1.91 at week 52) were associated with P2 sustained remission in this reduced-dose combination group (table). Predictors of P2 sustained remission in the MTX group included: achievement of DAS28 LDA over weeks 13-52 (49% vs 23%; P=0.044), younger age at BL, and lower levels of CRP at week 52. Predictors in the PBO group were: seronegative status at BL for anticyclic citrullinated peptide (seronegative vs seropositive: 48% vs 11%; P=0.001) and for rheumatoid factor (41% vs 11%; P=0.005) antibodies.

Table. Baseline and response predictors of sustained remission for active treatment groups.
Predictor	Quartiles of Response, n/N (%)				P value*
ETN 25   mg+MTX
First DAS28 remission	Days 0–57	58–179	180–273	≥274	0.003
	12/15 (80)	16/20 (80)	8/16 (50)	4/12 (33)
First DAS28 LDA	Days 0–29	30–57	58–183	≥184	0.041
	12/14 (86)	12/20 (60)	10/15 (67)	6/14 (43)
Mean DAS 28, week 52	DAS28 ≤1.55	>1.55–1.91	>1.91–2.16	>2.16	0.014
	14/16 (88)	11/16 (69)	7/15 (47)	8/16 (50)
MTX
Age, BL	19–39 years	40–48	49–60	≥61	0.024
	11/15 (73)	8/22 (37)	2/15 (13)	5/13 (39)
CRP level, week 52	0–0.5 mg/L	>0.5–1.09	>1.09–2.91	>2.91	0.005
	9/16 (56)	8/14 (57)	6/18 (33)	2/16 (13)
*Mantel-Haenszel chi-square correlation (trend) test.

Conclusion: Early onset of response to induction therapy with etanercept plus MTX predicted sustained remission with the reduced-dose combination maintenance regimen. These results are clinically important as prompt identification of patients unlikely to reach target responses may promote more timely adjustments in therapy and ultimately improved long-term outcomes.

References: 1. Smolen JS, et al. Ann Rheum Dis 2010;69: 964-75. 2. Emery P, et al. Ann Rheum Dis 2012;71:989-92.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-response-to-full-dose-etanercept-plus-methotrexate-induction-therapy-predicts-sustained-remission-with-reduced-dose-combination-therapy-in-early-rheumatoid-arthritis-patients/