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Randomized Controlled Trial
. 2016 Aug 16:354:i4205.
doi: 10.1136/bmj.i4205.

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

Espen A Haavardsholm  1 , Anna-Birgitte Aga  2 , Inge Christoffer Olsen  2 , Siri Lillegraven  2 , Hilde B Hammer  2 , Till Uhlig  2 , Hallvard Fremstad  3 , Tor Magne Madland  4 , Åse Stavland Lexberg  5 , Hilde Haukeland  6 , Erik Rødevand  7 , Christian Høili  8 , Hilde Stray  9 , Anne Noraas  10 , Inger Johanne Widding Hansen  11 , Gunnstein Bakland  12 , Lena Bugge Nordberg  2 , Désirée van der Heijde  13 , Tore K Kvien  2
Affiliations
Randomized Controlled Trial

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

Espen A Haavardsholm et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Protocol for escalation of disease modifying anti-rheumatic (DMARD) treatment. If patient responds or reaches target, current treatment is continued. *In patients with high disease activity and risk factors for progressive joint destruction, rescue option is available which includes moving to step 5 (introduce first biologic). †This step requires signs of ongoing inflammatory activity. TNF=tumour necrosis factor
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Fig 2 Trial profile. DMARD=disease modifying anti-rheumatic drug; RA=rheumatoid arthritis
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Fig 3 Top left: Disease Activity Score (DAS) over 24 months; least square mean estimates of DAS at all visits derived from mixed effects longitudinal model adjusted for baseline value and stratification factors. Top right: proportion of patients who achieved DAS remission over 24 months derived from logistic regression model. Bottom left: proportion of patients who achieved Simplified Disease Activity Index (SDAI) remission over 24 months derived from logistic regression model. Bottom right: proportion of patients who achieved American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) boolean remission over 24 months from logistic regression model. Bars indicate 95% confidence limits
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Fig 4 Cumulative probability plot of change between baseline and 24 months in van der Heijde modified Sharp score
See this image and copyright information in PMC

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