Background/Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line pharmacotherapy in axial spondyloarthritis (axSpA) but are recommended for use at the lowest effective dose for the shortest possible time due to safety concerns. Although NSAID discontinuation is common in clinical practice after response to biologic therapy in axSpA patients, its impact has not been evaluated in prospective controlled trials. The SPARSE trial was conducted to assess the effects of etanercept (ETN) on NSAID intake as measured by the ASAS-NSAID score¹and conventional clinical outcomes in axSpA.

Methods

In the initial 8-week, double-blind (DB), placebo (PBO)-controlled period, patients with active (mini BASDAI ≥4) axSpA (ASAS criteria) despite optimal NSAID intake were randomized to ETN 50 mg or PBO once weekly for 8 weeks. All patients were advised to taper/stop their NSAID intake (self-reported diary) during the study treatment period. Completers were eligible for ETN 50 mg in the subsequent 8-week open-label (OL) period. ASAS-NSAID scores were calculated according to ASAS recommendations.¹ The primary endpoint, the change from baseline (BL) to week 8 in the ASAS-NSAID score, was analyzed using an analysis of covariance (ANCOVA).

Results

In 90 randomized patients at BL, mean age (±SD) was 38.9±11.8 years; disease duration, 5.7±8.1 years; 62% were male; 66% were HLA-B27 positive; and 50% were MRI sacroiliitis positive. Mean ASAS-NSAID scores at BL (ETN vs PBO: 98.2±39.0 vs 93.0±23.4), BASDAI (6.0±1.7 vs 5.9±1.5), and BASFI (5.2±2.1 vs 5.1±2.2) were similar between groups. A between-group difference in changes in ASAS-NSAID scores of -27.3 (P=0.002) favoring ETN was observed at week 8 (table). Significantly more patients in the ETN vs PBO group achieved BASDAI50 and ASAS40 at week 8. Significant reductions in ASAS-NSAID scores were seen in the ETN/ETN group from BL to week 16 and in the PBO/ETN group from week 8 to 16 (table); response rates increased in the ETN/ETN and PBO/ETN groups for most clinical endpoints in the OL period.

Table. Effects of ETN vs PBO in patients with axSpA (ITT).
	Wk 8 (DB), N/n (%)		Wk 16 (OL), N/n (%)
Endpoint	ETN (n=42)	PBO (n=48)	ETN/ETN (n=39)	PBO/ETN (n=44)
NSAID-freea	16/33 (48)	8/40 (20)*	—	—
BASDAI50a	16/41 (39)	8/45 (18)†	15/28 (54)	18/37 (49)
ASAS20a	16/36 (44)	10/42 (24)	18/28 (64)	23/36 (64)
ASAS40a	16/36 (44)	9/42 (21)†	16/28 (57)	20/36 (56)
Parameter	Mean Change (95%CI/SD)
	BL to Wk 8		BL to Wk 16	Wk 8 to Wk 16
ASAS-NSAID scoreb	-63.9 (-76.0, -51.8)	-36.6 (-48.3, -24.9)*	-65.9 (-87.0, -44.9)‡	-39.2 (-52.9, -25.5)‡
	BL to Wk 8		BL to Wk 16
BASDAIc	-2.0 (-2.6, -1.4)	-1.1 (-1.7, -0.5)	-2.6 (1.8)	-3.0 (2.1)
BASFIc	-1.7 (-2.3, -1.1)	-0.8 (-1.3, -0.2)†	-1.8 (2.5)	-2.3 (1.9)
*P<0.01, ETN vs PBO; †P<0.05, ETN vs PBO; ‡P<0.0001, BL vs wk 16. aDB period: logistic regression with relevant BL score and treatment in model; OL period: descriptive statistics, observed cases (OC). bDB: ANCOVA, with BL score and treatment in model, LOCF, with imputation of missing data; OL: linear regression, OC, no imputation. cDB: ANCOVA, LOCF; OL: descriptive statistics, OC.

Conclusion

In this population of patients with axSpA, etanercept was associated with clinically relevant NSAID-sparing effects in addition to significant improvements in conventional clinical outcomes.

Reference: 1. Dougados M, et al. Ann Rheum Dis 2011;70(2):249-51.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-the-nonsteroidal-anti-inflammatory-drug-sparing-effect-of-etanercept-in-axial-spondyloarthritis-results-of-a-multicenter-randomized-double-blind-placebo-controlled-trial/