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Effects of ixekizumab treatment on structural changes in the sacroiliac joint: MRI assessments at 16 weeks in patients with non-radiographic axial spondyloarthritis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Walter P. Maksymowych
  • Xenofon Baraliakos
  • Robert G. Lambert
  • Robert Landewé
  • David Sandoval
  • Hilde Carlier
  • Jeffrey Lisse
  • Xiaoqi Li
  • Maja Hojnik
  • Mikkel Østergaard
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Background: There is limited understanding regarding the inhibition of structural damage in the sacroiliac joint of patients with non-radiographic axial spondyloarthritis. This study evaluated the effect of the interleukin-17A inhibitor ixekizumab versus placebo on structural lesions in the sacroiliac joints as assessed by MRI at week 16 in patients with non-radiographic axial spondyloarthritis from the COAST-X study. Methods: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly allocated to placebo or double-blind ixekizumab 80 mg every 4 weeks (Q4W) or 2 weeks (Q2W), with an 80 mg or 160 mg starting dose. We report a post-hoc analysis of 266 patients with available MRI scans from baseline and week 16. MRI scans were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural score (SSS) method independently by two masked readers. Treatment comparisons used analysis of covariance based on observed cases. Correlations were evaluated among changes in SPARCC SSS for erosion, fat lesions, and backfill, and between changes in SPARCC SSS and sacroiliac joint inflammation scores and clinical measures. COAST-X was registered with ClinicalTrials.gov, NCT02757352. Findings: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled to the COAST-X study. 290 (96%) of 303 participants completed the week 16 visit (95 in the ixekizumab Q4W group, 98 in the ixekizumab Q2W group, and 97 in the placebo group), and MRI scans were available for 266 patients at baseline and week 16 (85 in the ixekizumab Q4W group, 91 in the ixekizumab Q2W group, and 90 in the placebo group). Changes from baseline to week 16 in mean SPARCC SSS for erosion were −0·39 for ixekizumab Q4W (p=0·003 vs placebo), −0·40 for ixekizumab Q2W (p=0·002), and 0·16 for placebo; for fat lesions: 0·16 for ixekizumab Q4W (p=0·013), 0·10 for ixekizumab Q2W (p=0·067), and −0·04 for placebo; and for backfill: 0·21 for ixekizumab Q4W (p=0·011), 0·22 for ixekizumab Q2W (p=0·006), and −0·10 for placebo. Ankylosis did not change. Effects of ixekizumab versus placebo on structural changes were most pronounced in patients with baseline inflammation in the sacroiliac joints. Changes from baseline at week 16 in erosion, fat lesions, and backfill were correlated. Interpretation: Although the clinical relevance is not yet clear, patients with non-radiographic axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment. Funding: Eli Lilly and Company.

OriginalsprogEngelsk
TidsskriftThe Lancet Rheumatology
Vol/bind4
Udgave nummer9
Sider (fra-til)e626-e634
ISSN2665-9913
DOI
StatusUdgivet - sep. 2022

Bibliografisk note

Funding Information:
The authors would like to thank Stephanie Strakbein, Swati Dutta, and Srikanth Khati for assistance with performing the statistical analyses and David Henry Adams, for study contributions. This study was sponsored by Eli Lilly and Company. Lydia Morris, Gina Coudriet, and Barbara Nambu, employees of Syneos Health, provided writing support. Cynthia Rae Abbott, an employee of Syneos Health, provided editorial support. Data was verified by Cynthia Rae Abbott and Dana Schamberger, employees of Syneos Health, and So Young Park, an employee of Eli Lilly and Company.

Funding Information:
The authors would like to thank Stephanie Strakbein, Swati Dutta, and Srikanth Khati for assistance with performing the statistical analyses and David Henry Adams, for study contributions. This study was sponsored by Eli Lilly and Company. Lydia Morris, Gina Coudriet, and Barbara Nambu, employees of Syneos Health, provided writing support. Cynthia Rae Abbott, an employee of Syneos Health, provided editorial support. Data was verified by Cynthia Rae Abbott and Dana Schamberger, employees of Syneos Health, and So Young Park, an employee of Eli Lilly and Company.

Funding Information:
WPM is Chief Medical Officer of CARE Arthritis and has acted as a paid consultant or participated in advisory boards for AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, and UCB; received research or educational grants from AbbVie, Novartis, Pfizer, and UCB; and received speaker fees from AbbVie, Janssen, Novartis, Pfizer, and UCB. XB has received honoraria or research grants from, or participated in advisory boards for, AbbVie, Amgen, BMS, Chugai, Galapagos, Gilead, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. RGL has received consulting fees from CARE Arthritis, and Image Analysis Group. RL reports honoraria for consultancy and lectures, and grants to the institution from with AbbVie, Astra-Zeneca, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Gilead, Galapagos, Glaxo-Smith-Kline, Novartis, Pfizer, UCB; has received research grants from AbbVie, Novartis, Pfizer, and UCB; and is director of Imaging Rheumatology, which is a registered company under Dutch Law. DS, HC, JL, XL, and MH are employees and shareholders of Eli Lilly and Company. MØ has received research grants from AbbVie, BMS, Merck, Celgene, and Novartis and speaker or consultancy fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB.

Publisher Copyright:
© 2022 Elsevier Ltd

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