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Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial
  1. Margreet Kloppenburg1,2,
  2. Roberta Ramonda3,
  3. Klaus Bobacz4,
  4. Wing-Yee Kwok1,
  5. Dirk Elewaut5,6,
  6. Tom W J Huizinga1,
  7. Féline P B Kroon1,
  8. Leonardo Punzi3,
  9. Josef S Smolen4,
  10. Bert Vander Cruyssen5,
  11. Ron Wolterbeek7,
  12. Gust Verbruggen5,
  13. Ruth Wittoek5
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy
  4. 4 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  5. 5 Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
  6. 6 VIB inflammation Research Center, Ghent University, Ghent, Belgium
  7. 7 Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Professor Margreet Kloppenburg, Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; g.kloppenburg{at}lumc.nl

Abstract

Objective Hand osteoarthritis is a prevalent disease with limited treatment options. Since joint inflammation is often present, we investigated tumour necrosis factor (TNF) as treatment target in patients with proven joint inflammation in a proof-of-concept study.

Methods This 1-year, double-blind, randomised, multicentre trial (NTR1192) enrolled patients with symptomatic erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal anti-inflammatory drug washout were randomised to etanercept (24 weeks 50 mg/week, thereafter 25  mg/week) or placebo. The primary outcome was Visual Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS, n=54) and MRIs (n=20)).

Results Of 90 patients randomised to etanercept (n=45) or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was not statistically significantly different (−5.7 (95% CI −15.9 to 4.5), p=0.27 at 24 weeks; − 8.5 (95% CI −18.6 to 1.6), p=0.10 at 1  year; favouring etanercept). In prespecified per-protocol analyses of completers with pain and inflammation at baseline (n=61), MD was −11.8 (95% CI −23.0 to −0.5) (p=0.04) at 1  year. Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD 2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD −0.22 (95% CI −0.35 to −0.09), p = 0.001); this was more pronounced in joints with baseline inflammation.

Conclusion Anti-TNF did not relieve pain effectively after 24 weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for effects on subchondral bone in actively inflamed joints, but future studies to confirm this are warranted.

  • hand osteoarthritis
  • TNF-alpha
  • treatment
  • inflammation

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Footnotes

  • GV and RW are last authors.

  • Handling editor Francis Berenbaum

  • Contributors MK was the principal investigator and contributed to study design, data collection, data analysis, data interpretation and writing of the report. RR, W-YK, KB, GV contributed to study design, data collection, data interpretation and writing of the report. DE, TWJH, LP, JSS contributed to study design, data interpretation and writing of the report. FPBK, BVC contributed to data analysis, data interpretation and writing of the report. RWo contributed to data analysis and writing of the report. RWi contributed to study design, data collection, data analysis, data interpretation and writing of the report.

  • Funding This study was funded by Pfizer.

  • Competing interests MK reports an unrestricted grant paid to the institution and study medication free of charge from Pfizer (Wyeth) during the conduct of the study, outside the submitted work. MK reports advisory board fees from Levicept, GlaxoSmithKline, AbbVie, Merck and Pfizer, grants from IMI-EFPIA APPROACH, grants from Pfizer, and other from AbbVie. W-YK reports an unrestricted grant from Pfizer (Wyeth) during the conduct of the study. TWJH/Department of Rheumatology LUMC has received grants/lecture fees/consultancy fees from Merck, UCB, Bristol-Myers Squibb, Pfizer, Roche, Sanofi-Aventis, Crescendo Bioscience and Eli Lilly. JSS reports grants from AbbVie, Lilly, Pfizer and Roche, personal fees from AbbVie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Lilly, MedImmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB, outside the submitted work. RWi reports having a patent GUSS issued.

  • Patient consent Obtained.

  • Ethics approval The trial was approved by the medical ethical committee in each participating centre.

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

  • Data sharing statement Additional documents (study protocol and statistical analysis plan) are available upon request (contact the corresponding author).

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