Background/Purpose

Previous studies evaluating various treatment strategies indicate that disease duration is a key determinant of outcomes in rheumatoid arthritis (RA). While data suggest that RA patients with longer established disease do not respond as well to treatment compared with patients with early disease, this evidence is limited. The objective of this sub-analysis was to determine the effect of disease duration on treatment response in patients with moderately active RA receiving induction therapy with etanercept (ETN) plus methotrexate (MTX) for 36 weeks in the PRESERVE study.

Methods

In the induction phase of the PRESERVE study, patients with moderately active RA (DAS28 >3.2 and ≤5.1) despite stable doses of oral MTX received open-label ETN 50 mg QW plus MTX (titrated to ≤25 mg/week as needed through week 28) for 36 weeks. Patients were stratified by disease duration at baseline:  0–≤6 mo, >6mo–≤2 yr, >2yr–≤5 yr, >5yr–≤10 yr and >10 yr. Baseline demographic and disease characteristics and treatment response (DAS28, CDAI, HAQ) were compared across disease duration categories.  Analyses using observed cases (OC) were conducted in all patients who received ≥1 ETN/MTX dose (mITT population).

Results

A total of 833 patients receiving ETN50/MTX (baseline disease duration: 0–≤6 mo, n=41; >6mo–≤2 yr, n=198; >2yr–≤5 yr, n=204; >5yr–≤10 yr, n=172; >10 yr, n=218) were included. At baseline, more established disease was significantly associated with higher age and a higher swollen joint count (Table). In addition, a significantly greater proportion of patients with longer disease duration were rheumatoid factor and CCP3 antibody positive. HAQ score at baseline significantly correlated with greater duration of disease while baseline DAS28 and CDAI were similar across disease duration subgroups. Significant changes from baseline in DAS28, CDAI and HAQ were observed at Week 4 and at all time-points up to Week 36 in all disease duration categories (all P<0.0001). These observed improvements in clinical measures of disease activity and quality of life were similar among disease duration subgroups (Table).

Characteristic	Disease Duration					P-value
	0–≤6 mo (n=43)	>6mo–≤2 y (n=129)	>2yr–≤5 y (n=157)	>5yr–≤10 y (n=117)	>10 y (n=157)
Baseline, Mean (SD) (unless stated)
Age	47.7 (12.1)	46.3 (12.2)	46.3 (12.0)	48.7 (12.1)	52.0 (10.6)	<0.001*
RF Positive, n (%)	32 (78.0)	117 (59.7)	146 (71.9)	134 (77.9)	173 (80.1)	<0.001†
CCP3 Ab Positive, n (%)	34 (82.9)	126 (64.3)	157 (77.7)	143 (83.1)	181 (84.2)	<0.001†
Swollen Joint Count	3.2 (1.9)	3.5 (2.4)	3.6 (2.2)	3.9 (2.9)	4.4 (2.9)	0.001*
DAS28	4.4 (0.5)	4.3 (0.5)	4.4 (0.4)	4.4 (0.4)	4.4 (0.4)	0.401*
CDAI	17.2 (3.4)	17.8 (4.9)	17.4 (4.7)	17.7 (5.2)	18.5 (5.3)	0.180*
HAQ	1.1 (0.6)	1.1 (0.6)	1.1 (0.6)	1.2 (0.6)	1.3 (0.6)	0.003*
Week 36, Adjusted mean change (SE)
DAS28	-2.0 (0.2)	-2.0 (0.1)	-2.1 (0.1)	-2.0 (0.1)	-1.9 (0.1)	NS‡
CDAI	-12.1 (1.0)	-12.2 (0.4)	-12.2 (0.4)	-12.0 (0.5)	-11.3 (0.4)	NS‡
HAQ	-0.52 (0.08)	-0.55 (0.04)	-0.59 (0.03)	-0.57 (0.04)	-0.58 (0.03)	NS‡
*1-way ANOVA; †Chi-square; ‡Not significant for all pair-wise comparisons

Conclusion

In the PRESERVE trial, improvements in clinical outcomes in response to open-label therapy with ETN plus MTX in patients with moderately active RA was largely unaffected by differences in disease duration before treatment initiation. The use of induction with ETN plus MTX in moderate RA may prevent the poorer outcomes often associated with longer disease duration.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-disease-duration-on-clinical-outcomes-in-moderate-rheumatoid-arthritis-patients-treated-with-etanercept-plus-methotrexate-in-the-preserve-study/