Discriminant Capacity of Clinical Efficacy and Nonsteroidal Antiinflammatory Drug-sparing Endpoints, Alone or in Combination, in Axial Spondyloarthritis

Maxime Dougados; Emily Wood; Laure Gossec; Arnaud Dubanchet; Isabelle Logeart; Désirée van der Heijde

doi:10.3899/jrheum.150378

Discriminant Capacity of Clinical Efficacy and Nonsteroidal Antiinflammatory Drug-sparing Endpoints, Alone or in Combination, in Axial Spondyloarthritis

J Rheumatol. 2015 Dec;42(12):2361-8. doi: 10.3899/jrheum.150378. Epub 2015 Nov 15.

Authors

Maxime Dougados¹, Emily Wood², Laure Gossec², Arnaud Dubanchet², Isabelle Logeart², Désirée van der Heijde²

Affiliations

¹ From the Paris Descartes University; Department of Rheumatology-Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP); Institut national de la santé et de la recherche médicale (INSERM; U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique; Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; Pfizer, Paris, France; Statistical Consultancy, Quanticate Ltd., Hitchin, UK; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.M. Dougados, MD, Paris Descartes University, and Department of Rheumatology-Hôpital Cochin, AP-HP, and INSERM (U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; E. Wood, MSc, Statistical Consultancy, Quanticate Ltd.; L. Gossec, MD, PhD, Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; A. Dubanchet, MD, Pfizer; I. Logeart, MD, Pfizer; D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center. maxime.dougados@cch.aphp.fr.
² From the Paris Descartes University; Department of Rheumatology-Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP); Institut national de la santé et de la recherche médicale (INSERM; U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique; Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; Pfizer, Paris, France; Statistical Consultancy, Quanticate Ltd., Hitchin, UK; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.M. Dougados, MD, Paris Descartes University, and Department of Rheumatology-Hôpital Cochin, AP-HP, and INSERM (U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; E. Wood, MSc, Statistical Consultancy, Quanticate Ltd.; L. Gossec, MD, PhD, Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; A. Dubanchet, MD, Pfizer; I. Logeart, MD, Pfizer; D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center.

PMID: 26568588
DOI: 10.3899/jrheum.150378

Abstract

Objective: Using data from a randomized, double-blind, placebo-controlled study, we assessed the capacity of clinical and nonsteroidal antiinflammatory drug (NSAID)-sparing endpoints, alone and in combination, to discriminate between treatment effects in axial spondyloarthritis (axSpA).

Methods: Patients with active NSAID-resistant axSpA received etanercept (ETN) 50 mg/week or placebo for 8 weeks and tapered/discontinued NSAID. In posthoc logistic regression analyses, OR were calculated that indicated the capacity of the following endpoints to discriminate between the effects of ETN and placebo at Week 8: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50; BASDAI ≤ 3; Assessment of Spondyloarthritis international Society (ASAS) 20; ASAS40; Ankylosing Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP) < 1.3 and ASDAS-CRP < 2.1; ≥ 50% decrease from baseline in ASAS-NSAID score, score < 10, and score = 0; and each clinical and/or each NSAID measure.

Results: In 90 randomized patients (ETN, n = 42; placebo, n = 48), disease activity was similar between groups at baseline: mean (± SD) BASDAI (ETN vs placebo) 6.0 ± 1.6 versus 5.9 ± 1.5. NSAID intake was high: ASAS-NSAID score 98.2 ± 39.0 versus 93.0 ± 23.4. OR ranged from 1.6 (95% CI 0.5-5.4) for ASDAS-CRP < 1.3 to 5.8 (95% CI 1.2-29.1) for BASDAI50 and NSAID score of 0; most measures (34/45) reached statistical significance (α = 0.05) favoring ETN. Most combined outcome variables using OR were more discriminant than single outcome measures.

Conclusion: These findings suggest that changes in NSAID intake during treatment do not prevent demonstration of clinically relevant effects of biologic treatment, and combined (i.e., clinical with NSAID-sparing) endpoints were frequently more discriminant than single (i.e., clinical) endpoints. ClinicalTrials.gov (NCT01298531).

Keywords: ASAS; ASDAS; AXIAL SPONDYLOARTHRITIS; BASDAI; ETANERCEPT; NONSTEROIDAL ANTIINFLAMMATORY DRUG.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
Confidence Intervals
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Etanercept / administration & dosage*
Female
Follow-Up Studies
Humans
Logistic Models
Male
Middle Aged
Radiography
Risk Assessment
Severity of Illness Index
Spondylarthritis / diagnostic imaging
Spondylarthritis / drug therapy*
Spondylarthritis / physiopathology*
Treatment Outcome

Substances

Anti-Inflammatory Agents, Non-Steroidal
Etanercept

Associated data

ClinicalTrials.gov/NCT01298531