Background/Purpose: Although frequently effective, treatment with synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) does not adequately control disease activity in all patients. Prompt identification of patients unlikely to achieve long-term therapeutic targets is a clinically relevant strategy that may allow for timely alterations in treatment and optimal outcomes. The objective of this subanalysis was to determine disease characteristics of responders and non-responders to treatment with etanercept (ETN) plus methotrexate (MTX) in patients with early, active moderate-to-severe RA participating in Period 1 of the PRIZE study.

Methods: MTX- and biologic-naïve RA patients (DAS28 >3.2; symptom onset ≤12 months from enrollment) received ETN 50 mg QW and MTX (ETN50/MTX) for 52 wk. At the investigator’s discretion, the initial 10 mg/wk MTX dose was titrated to a maximum 25 mg/wk; corticosteroid boosts were administered to patients not achieving low disease activity (LDA; DAS28 ≤3.2) at week 13 and/or 26. Prior DMARD, NSAID, and corticosteroid use and disease characteristics were analyzed in responders at week 39 and 52 (defined as patients with DAS28 ≤3.2 and DAS28 <2.6, respectively) and non-responders at week 39 and 52 (defined as patients with DAS28 >3.2 and DAS28 ≥2.6, respectively, or unsatisfactory response due to efficacy [based on investigators’ judgment]), as specified by the study protocol and using a last observation carried forward approach.

Results: Of 306 patients receiving ETN50/MTX in Period 1, 30 (9.8%) and 24 (7.8%) were non-responders at wk 39 and 52, respectively; 7 (2.3%) had an unsatisfactory response. Among responders (n=194) and non-responders (n=61), 33 (17.0%) and 3 (4.9%) received prior DMARDs, respectively (P=0.018); 80 (41.2%) and 22 (36.1%), prior corticosteroids (P=0.472); and 129 (66.5%) and 31 (50.8%), prior NSAIDs (P=0.027). A lower proportion of responders received corticosteroid boosts than non-responders at week 13 (29.0% v 63.9%) and week 26 (17.0% v 61.7%). DAS28, SDAI, and HAQ values were significantly higher in non-responders at baseline (P<0.01) and from weeks 2-52 (P<0.0001; Table). Significantly lower proportions of non-responders had normal HAQ (≤0.5) vs responders from week 2-52 (P<0.0001). Both responders and non-responders had improved disease activity and function with treatment over time, but non-responders had slower rates of response. Both groups appeared to achieve a steady state by week 39.

 

Table: Differences in disease characteristics at baseline (BL) and weeks 39 and 52 in protocol-specified responders and non-responders to ETN50/MTX at week 52 (LOCF)
Characteristic	Mean (SD)/Adjusted Mean Change (SE)		Mean Difference (95% CI)	P Value
	Responders	Non-Responder
DAS28 at BL	5.9 (1.1)	6.3 (1.1)		0.004
Week 39      Week 52	2.0 (0.7)/-4.0 (0.06) 1.8 (0.6)/-4.1 (0.06)	3.8 (1.5)/-2.3 (0.12) 4.1 (1.4)/-2.0 (0.11)*	-1.6 (-2.0, -1.4) -2.1 (-2.3, -1.8)	<0.0001 <0.0001
SDAI at BL	36.4 (13.5)	41.8 (14.7)		0.008
Week 39      Week 52	2.8 (2.8)/-34.5 (0.6) 2.0 (1.9)/-35.4 (0.6)	15.8 (15.8)/-23.0 (1.0) 16.6 (15.8)/-22.3 (1.0)*	-11.5 (-13.9, -9.2) -13.1 (-15.4, -10.8)	<0.0001 <0.0001
HAQ at BL	1.2 (0.6)	1.5 (0.7)		0.0007
Week 39      Week 52	0.3 (0.4)/-0.9 (0.0) 0.3 (0.4)/-1.0 (0.0)	0.9 (0.7)/-0.5 (0.1) 0.9 (0.7)/-0.5 (0.1)*	-0.5 (-0.6, -0.3) -0.5 (-0.6, -0.4)	<0.0001 <0.0001
	% of Patients (95% CI)		P Value
Normal HAQ (≤0.5)
Week 39      Week 52	77.8 (16.5, 28.7) 81.4 (75.2, 86.7)	34.4 (52.3, 77.3) 36.1 (50.6, 75.8)*	<0.0001 <0.0001
*≥50% of patients were discontinued at week 39 and were carried forward to week 52.

Conclusion: In Period 1 of the PRIZE trial, patients with early, moderate-to-severe RA who did not meet protocol-specified response criteria after treatment with etanercept plus methotrexate showed higher levels of disease activity and greater functional disability at baseline and throughout the period, and were more likely to require corticosteroid boosts, compared with patients who satisfied response criteria.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characteristics-of-protocol-specified-respondersnon-responders-treated-with-etanercept-plus-methotrexate-in-period-1-of-the-prize-study/