title: Discriminant Capacity of Clinical Efficacy and Nonsteroidal Antiinflammatory Drug-sparing Endpoints, Alone or in Combination, in Axial Spondyloarthritis.
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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: 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.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: 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.
authors.forename: Emily
authors.initials: E
authors.lastname: Wood
authors.affiliation: 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.
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
authors.affiliation: 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.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Dubanchet
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Logeart
authors.affiliation: 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.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068800:Etanercept / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011859:Radiography; D018570:Risk Assessment; D012720:Severity of Illness Index; D025241:Spondylarthritis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068800:Etanercept
keywords: ASAS; ASDAS; AXIAL SPONDYLOARTHRITIS; BASDAI; ETANERCEPT; NONSTEROIDAL ANTIINFLAMMATORY DRUG