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Original article
Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies
  1. Jürgen Braun1,
  2. Atul Deodhar2,
  3. Robert Landewé3,
  4. Xenofon Baraliakos1,
  5. Corinne Miceli-Richard4,
  6. Joachim Sieper5,
  7. Erhard Quebe-Fehling6,
  8. Ruvie Martin7,
  9. Brian Porter7,
  10. Kunal K Gandhi7,
  11. Désirée van der Heijde8,
  12. on behalf of the MEASURE 1 and MEASURE 2 study groups
  1. 1 Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany
  2. 2 Oregon Health & Science University, Portland, Oregon, USA
  3. 3 University of Amsterdam and Atrium Medical Centre, Amsterdam, The Netherlands
  4. 4 Paris Descartes University, Department of Rheumatology -Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France
  5. 5 Charité University Medicine Berlin, Berlin, Germany
  6. 6 Novartis Pharma AG, Basel, Switzerland
  7. 7 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
  8. 8 Leiden University Medical Centre, Leiden, The Netherlands
  1. Correspondence to Prof. Jürgen Braun; j.braun{at}rheumazentrumruhrgebiet.de

Abstract

Objective To evaluate the magnitude of response to secukinumab treatment over 3 years in patients with ankylosing spondylitis (AS) grouped by baseline C-reactive protein (CRP) levels in a pooled study of two pivotal phase III studies: MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375).

Methods This post hoc analysis pooled data from all patients with available baseline CRP in the two studies who received subcutaneous secukinumab 150  mg (approved dose; N=197) or placebo (N=195). Assessed efficacy endpoints included Assessments of SpondyloArthritis international Society (ASAS)20/40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, AS Disease Activity Score inactive disease and ASAS partial remission among patients grouped by baseline CRP based on central laboratory cut-off <5  mg/L (normal) or ≥5  mg/L (elevated) and a cut-off <10  mg/L or ≥10  mg/L.

Results At baseline, 36.5% (143/392) patients had normal and 63.5% (249/392) had elevated CRP. At week 16, ASAS20/40 response rates were higher for secukinumab versus placebo in normal (56.9%/34.7% vs 28.2%/7.0%; p<0.01/p<0.001) and in elevated (63.2%/42.4% vs 29.0%/15.3%; both p<0.0001) CRP groups. Improvement was reported for all outcomes (p<0.05) in both groups, except for ASAS partial remission in the normal CRP group, where a numerical difference 12.5% vs 2.8%, p=0.07) was observed. Similar trends of improvement were observed in the <10  and ≥10  mg/L groups across all efficacy outcomes at week 16. Treatment responses to secukinumab in all CRP groups further improved over 156 weeks.

Conclusion Secukinumab 150  mg demonstrated rapid and sustained efficacy in patients with AS irrespective of baseline CRP, with greater magnitude of response in patients with more elevated CRP.

  • ankylosing spondylitis
  • DMARDs (biologic)
  • inflammation
  • cytokine
  • spondyloarthritis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Presented at This manuscript based on the work previously presented at the American College of Rheumatology (ACR) Annual Meeting, November 3-8, 2017, San Diego, United States. JB, JS, RL, et al. Secukinumab Demonstrates Rapid and Sustained Efficacy in Ankylosing Spondylitis Patients with Normal or Elevated Baseline CRP Levels: Pooled Analysis of Two Phase 3 Studies [abstract]. Arthritis Rheumatol 2017;69(Suppl 10).

  • Contributors All authors participated in the interpretation of data, critical review and final approval of the manuscript.

  • Funding The study was sponsored by Novartis Pharma AG, Basel, Switzerland and designed by the scientific steering committee and Novartis personnel. Medical writing support was funded by Novartis.

  • Competing interests JB has received research grant from AbbVie, Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB, and served as consultant or paid speaker for AbbVie, Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB. AD has received research grants from AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB, and has received honorarium for serving on the advisory boards of Eli Lilly, Janssen, Novartis, Pfizer and UCB. RL has received research grant from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, served as consultant for AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, and paid speaker for Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth. XB has received research grant from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, served as consultant or paid speaker for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen. CMR has received research grant from AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, and Wyeth, served as consultant for Pfizer, Roche, UCB, Wyeth, and Merck, and paid speaker for Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, and Wyeth. JS has received research grant from AbbVie, Pfizer, and Merck, served as consultant for AbbVie, Pfizer, Merck, UCB, and Novartis, and paid speaker for AbbVie, Pfier, Merck, and UCB. EQF is an employee of Novartis. RM, BP, KKG are employees of Novartis and own Novartis stock. DVH served as consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB.

  • Patient consent Written informed consent was obtained from all screened patients.

  • Ethics approval The study was approved by the institutional review board or ethics committee at each participating site and was conducted according to the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Novartis is committed to sharing with qualified external researchers access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved the basis of scientific merit. All data provided is anonymised to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The data may be requested from the corresponding author of the manuscript.

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