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

IntroductionIn 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.MethodsIn 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).ResultsIn 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.ConclusionsIn patients with axSpA, etanercept was associated with clinically relevant NSAID-sparing effects in addition to significant improvements in conventional clinical outcomes.Trial registrationClinicalTrials.gov NCT01298531. Registered 16 February 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0481-5) contains supplementary material, which is available to authorized users.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers’ effectiveness in axial spondyloarthritis: results of a prospective, multicentre study

“…Secondary effectiveness endpoints were defined as either of the following:An improvement between baseline and the effectiveness visit: ASAS 40,24 ASAS 20,24 ASDAS clinically important improvement and major improvement25; reduction of at least 50% in the ASAS-NSAID score26; reduction on the baseline CRP (mg/L).A status after 12 weeks: ASDAS moderate disease activity (ASDAS MDA) and ASDAS inactive disease (ASDAS ID),25 respectively; an ASAS-NSAID score <10; and a CRP <6 mg/L at 12 weeks. …”

“…An improvement between baseline and the effectiveness visit: ASAS 40,24 ASAS 20,24 ASDAS clinically important improvement and major improvement25; reduction of at least 50% in the ASAS-NSAID score26; reduction on the baseline CRP (mg/L).…”

Tumour necrosis factor-α inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation

“…Three trials of axSpA populations were excluded because results were not available separately for the AS and nr-AxSpA populations. [41][42][43] One study of adalimumab appeared likely to be eligible but was excluded as it was only available as a ClinicalTrials.gov record, without any results or further study details. 44 One excluded study was an ongoing trial of golimumab (called GO-AHEAD).…”

“…As noted in main text, it is reasonable to assume patients receiving CC do not achieve a change from baseline (worsening or improvement) in BASDAI or BASFI as evidence from RAPID-axSpA, 64 ATLAS 61 and ABILITY-1 58 demonstrate that in the placebo arms of these studies where patients were essentially maintained on CC, patients did not achieve MCID for BASDAI or BASFI. Furthermore, Dougados et al 43 describe CC regimens as 'palliative at best, providing no alteration of the disease process'. This assumption is consistent with previous manufacturers' submissions to NICE in AS.…”

“…58 demonstrate that in the placebo arms of these studies in which patients were essentially maintained on CC, patients did not achieve MCID for BASDAI or BASFI. Furthermore, Dougados et al 43 describe CC regimens as 'palliative at best, providing no alteration of the disease process'. This assumption is consistent with previous manufacturers' submissions to NICE in AS.…”