Evaluation of the nonsteroidal anti-inflammatory drug-sparing effect of etanercept in axial spondyloarthritis: results of the multicenter, randomized, double-blind, placebo-controlled SPARSE study

Abstract

Introduction: In clinical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly discontinued after response to biologic therapy is achieved in patients with axial spondyloarthritis (axSpA), but the impact of NSAID discontinuation has not been assessed in prospective controlled trials. The aim of the SPARSE study was to evaluate the effects of the anti-tumor necrosis factor agent etanercept on NSAID intake and conventional clinical outcomes in axSpA patients.

Methods: In the double-blind, placebo-controlled period, patients with active (mini Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4) axSpA despite optimal NSAID intake were randomized to receive etanercept 50 mg or placebo once weekly for 8 weeks. All patients were advised to taper/discontinue their NSAID intake during the treatment period. NSAID intake was self-reported by diary and Assessment of SpondyloArthritis International Society (ASAS)-NSAID scores calculated based on ASAS recommendations. The primary endpoint was change from baseline to week 8 in ASAS-NSAID score (analysis of covariance).

Results: In 90 randomized patients at baseline, mean age (standard deviation) was 38.9 (11.8) years; disease duration, 5.7 (8.1) years; 59/90 (66%) were human leukocyte antigen-B27 positive; 51/90 (57%) had radiographic sacroiliitis; and 45/90 (50%) were magnetic resonance imaging sacroiliitis-positive. Mean ASAS-NSAID scores were similar between etanercept and placebo groups at baseline (98.2 (39.0) versus 93.0 (23.4)), as were BASDAI (6.0 (1.7) versus 5.9 (1.5)), and Bath Ankylosing Spondylitis Functional Index (5.2 (2.1) versus 5.1 (2.2)). Mean changes (SE) in ASAS-NSAID score from baseline to week 8 were -63.9 (6.1) and -36.6 (5.9) in the etanercept and placebo groups (between-group difference, -27.3; P = 0.002). Significantly higher proportions of patients receiving etanercept versus placebo had an ASAS-NSAID score <10 (46% versus 17%; P = 0.008) and ASAS-NSAID score of 0 (41% versus 14%; P = 0.013) at this time point. Significantly more patients in the etanercept versus placebo group achieved BASDAI50 (39% versus 18%; P = 0.032) and ASAS40 (44% versus 21%; P = 0.028) at week 8.

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

Trial registration: ClinicalTrials.gov NCT01298531. Registered 16 February 2011.

Figure 1

Patient flow through the double-blind and open-label phases. AE, adverse event; DB, double-blind; ETN, etanercept; OL, open-label; PBO, placebo.

Figure 2

Nonsteroidal anti-inflammatory drug–sparing effects. (A) Change in ASAS-NSAID score from baseline to week 8 in patients in the etanercept and placebo groups (primary analysis of primary endpoint). Analysis of covariance, LOCF, with imputation of missing diary data, in the ITT population. (B) Proportion of patients in the etanercept and placebo groups achieving other NSAID-sparing endpoints at week 8 of the double-blind period. LOCF, with imputation, ITT population (n = number of patients achieving endpoint; N = number of patients with analyzable data). (C) Mean ASAS-NSAID scores (± SD) in the etanercept/etanercept and placebo/etanercept groups in the double-blind and open-label phases. ASAS-NSAID scores were calculated for observed cases, with no imputation of missing diary data. ASAS-NSAID, Assessment of SpondyloArthritis International Society nonsteroidal anti-inflammatory drug use; ETN, etanercept; ITT, intent-to-treat; LOCF, last observation carried forward; NSAID, nonsteroidal anti-inflammatory drug; PBO, placebo; SD, standard deviation; SE, standard error.

Figure 3

Clinical efficacy. (A) Proportion of patients in the etanercept and placebo groups achieving clinical endpoints at week 8 of the double-blind period. Logistic regression, LOCF (except PASS, which was calculated in observed cases). (B) Proportion of patients in the etanercept and placebo groups achieving ASDAS-CRP disease activity states at week 8 of the double-blind period. Post hoc analysis of ITT population; n = number of patients with nonmissing ASDAS-CRP results at each visit. Inactive disease = ASDAS-CRP <1.3; moderate disease activity = 1.3 ≤ ASDAS-CRP <2.1; high disease activity = 2.1 ≤ ASDAS-CRP <3.5; very high disease activity = ASDAS-CRP ≥3.5. ASAS, Assessment of SpondyloArthritis International Society; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score based on C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; ITT, intent-to-treat; LOCF, last observation carried forward; PASS, patient acceptable symptom state.