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Research

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4205 (Published 16 August 2016) Cite this as: BMJ 2016;354:i4205
  1. Espen A Haavardsholm, professor and consultant rheumatologist1,
  2. Anna-Birgitte Aga, consultant rheumatologist1,
  3. Inge Christoffer Olsen, statistician1,
  4. Siri Lillegraven, trainee in rheumatology and senior researcher1,
  5. Hilde B Hammer, consultant rheumatologist and senior researcher1,
  6. Till Uhlig, professor of rheumatology1,
  7. Hallvard Fremstad, consultant rheumatologist,2,
  8. Tor Magne Madland, consultant rheumatologist3,
  9. Åse Stavland Lexberg, consultant rheumatologist4,
  10. Hilde Haukeland, consultant rheumatologist5,
  11. Erik Rødevand, consultant rheumatologist and head of department of rheumatology6,
  12. Christian Høili, consultant rheumatologist7,
  13. Hilde Stray, consultant rheumatologist8,
  14. Anne Noraas, consultant rheumatologist9,
  15. Inger Johanne Widding Hansen, consultant rheumatologist10,
  16. Gunnstein Bakland, consultant rheumatologist and head of department of rheumatology11 12,
  17. Lena Bugge Nordberg, research fellow1,
  18. Désirée van der Heijde, epidemiologist and professor of rheumatology1 13,
  19. Tore K Kvien, professor of rheumatology and head of department of rheumatology1
  1. 1Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, 0319 Oslo, Norway
  2. 2Department of Rheumatology, Ålesund Hospital, Ålesund, Norway
  3. 3Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
  4. 4Department of Rheumatology, Drammen Hospital, Drammen, Norway
  5. 5Department of Rheumatology, Martina Hansens Hospital AS, Sandvika, Norway
  6. 6Department of Rheumatology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  7. 7Department of Rheumatology, Hospital Østfold HF Moss, Grålum, Norway
  8. 8Haugesund Rheumatism Hospital AS, Haugesund, Norway
  9. 9The Rheumatology Clinic Dovland/Bendvold, Kristiansand, Norway
  10. 10Department of Rheumatology, Sørlandet Hospital HF, Kristiansand, Norway
  11. 11Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway
  12. 12Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway
  13. 13Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  1. Correspondence to: E A Haavardsholm e.a.haavardsholm{at}medisin.uio.no
  • Accepted 15 July 2016

Abstract

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy.

Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial.

Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015.

Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded.

Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years.

Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set.

Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events.

Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology.

Trial registration Clinical trials NCT01205854.

Footnotes

  • We thank all the patients who participated in the study, as well as the investigators and medical staff at all participating centres for their contributions to the study. We also thank Ellen Moholt, Camilla Fongen, and Maria K Jonsson for their contributions to the data collection.

  • Contributors: EAH and ABA designed the study; recruited and enrolled participants; collected, analysed, and interpreted data; and wrote the report. ICO designed the study, analysed and interpreted data, and wrote the report. SL and LBN analysed and interpreted data and wrote the report. HBH designed the study, recruited participants, interpreted data, and reviewed the manuscript. TU designed the study, recruited and enrolled participants, interpreted data, and reviewed the manuscript. HF, TMM, ÅSL, HH, ER, CH, HS, ANB, IJWH, and GB recruited and enrolled patients, interpreted data, and reviewed the manuscript. DvdH and TKK designed the study, interpreted data, and reviewed the manuscript. All authors have approved the final draft and vouch for the accuracy and completeness of the data and analyses. EAH is the guarantor.

  • Funding: This trial was supported by the Norwegian Research Council, Norwegian South-Eastern Health Region, Norwegian Women's Public Health Association, Norwegian Rheumatism Association, investigator initiated research grants from AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, and Roche Norway. Siemens Healthcare and GE Healthcare provided technical support regarding standardisation of ultrasound equipment. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: EAH has received research funding from Pfizer, UCB, Roche, MSD, and AbbVie for the submitted work, honorariums as a speaker from Pfizer, UCB, Roche, and AbbVie, and honorariums for development of educational material from Pfizer and has sat on advisory boards for Pfizer; ABA has sat on advisory boards for UCB, AbbVie, and Pfizer and received honorariums for development of educational material for UCB; HBH has received honorariums as a speaker from AbbVie, Bristol-Myers Squibb, Roche, UCB Pharma, and Pfizer; HH has sat on advisory boards for UCB and AbbVie; GB has received honorariums as a speaker from AbbVie and has sat on advisory boards for Pfizer; DvdH has received consultancy honorariums from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi, Eli Lilly, Galapagos, Merck, Novartis, Pfizer, Roche, Sanofi Aventis, Janssen, and UCB and is owner of Imaging Rheumatology; TKK has received consultancy honorariums from AbbVie, Bristol-Myers Squibb, Celltrion, Epirus, Hospira, Merck-Serono, MSD, Orion Pharma, Pfizer, and UCB; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study protocol and consent documents were approved by an independent ethics committee (the Regional Committee for Medical and Health Research Ethics South-East; reference number 2010/744) and appropriate institutional review boards.

  • Data sharing: The authors commit to making the relevant anonymised patient level data available on reasonable request.

  • Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Preliminary reports: Preliminary reports of the ARCTIC trial have been presented at the Annual Meeting of the American College of Rheumatology in San Francisco (10 November 2015) and the European League Against Rheumatism (EULAR) Annual Congress of Rheumatology in London (9 June 2016).

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) 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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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