Espen A. Haavardsholm

EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis

Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods The task force comprised an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.

High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study

Objectives: New effective therapies with particularly good effect on joint destruction have highlighted the need for reliable predictors of radiographic progression in rheumatoid arthritis (RA). Our objective was to assess the combined predictive role of a set of laboratory markers with regard to 10-year radiographic progression, and to examine the effect of anti-cyclic citrullinated peptide (anti-CCP) level. Methods: A cohort of 238 patients with RA was followed longitudinally for 10 years with the collection of clinical data and serum samples. 125 patients with radiographs of the hands available at both baseline and after 10 years were included in this study. Radiographs were scored according to the van der Heijde modified Sharp score. Baseline sera were analysed for C-reactive protein, erythrocyte sedimentation rate (ESR), anti-CCP, IgA rheumatoid factor (RF) and IgM RF. Logistic regression analyses were used to identify predictors of radiographic progression and to examine the effect of anti-CCP level. Results: Anti-CCP (OR 4.0; 95% CI 1.6 to 10.0) was the strongest independent predictor of radiographic progression. Female gender (OR 3.3; 95% CI 1.3 to 7.6), high ESR (OR 3.2; 95% CI 1.2 to 7.6) and a positive IgM RF (OR 3.1; 95% CI 1.2 to 7.9) were also independent predictors. Compared with the anti-CCP-negative patients, patients with low to moderate levels of anti-CCP (OR 2.6; 95% CI 0.9 to 7.2) and patients with high levels of anti-CCP (OR 9.9; 95% CI 2.7 to 36.7) were more likely to develop radiographic progression. Conclusions: Anti-CCP, IgM RF, ESR and female gender were independent predictors of radiographic progression and could be combined into an algorithm for better prediction. Patients with high levels of anti-CCP were especially prone to radiographic progression, indicating that the anti-CCP level may add prognostic information.

Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression.

Objectives: To examine the spectrum and severity of magnetic resonance imaging (MRI) findings in patients with early rheumatoid arthritis (RA), and to investigate the predictive value of MRI findings for subsequent development of conventional radiographic (CR) damage and MRI erosions. Methods: 84 consecutive patients with RA with disease duration <1 year were enrolled. Patients were treated according to standard clinical practice, and evaluated at baseline, 3, 6 and 12 months by core measures of disease activity, conventional radiographs of both hands and wrists and MRI of the dominant wrist. MR images were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging score (RAMRIS), and conventional radiographs according to the van der Heijde modified Sharp score. Results: MRI findings reflecting inflammation (synovitis, bone marrow oedema and tenosynovitis) decreased during follow-up, while there was a small increase in MRI erosion score and CR damage. The proportion of patients with erosive progression at 1 year was 48% for conventional radiography and 66% for MRI. Baseline MRI bone marrow oedema (score >2 RAMRIS units) was identified as an independent predictor of both CR (odds ratio = 2.77 (95% confidence interval (CI) 1.06 to 7.21)) and MRI erosive progression (B = 0.21 (95% CI 0.08 to 0.34)). Conclusions: MRI findings were common in early RA, and MRI bone marrow oedema was an independent predictor of radiographic damage. These results suggest that MRI scans of the dominant wrist may help clinicians to determine which patients need early and aggressive treatment to avoid subsequent joint damage.

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial

BACKGROUND TNF inhibitors have improved treatment of Crohns disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. METHODS The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. FINDINGS Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohns disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4·4%, 95% CI -12·7 to 3·9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively). INTERPRETATION The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases. FUNDING Norwegian Ministry of Health and Care Services.

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

This paper presents the wrist joint MR images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0–3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system—that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0–3 of bone oedema are illustrated, and for bone erosion, grades 0–3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.

The OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS): Definitions of Key Pathologies, Suggested MRI Sequences, and Preliminary Scoring System for PsA Hands

This article describes a preliminary OMERACT psoriatic arthritis magnetic resonance image scoring system (PsAMRIS) for evaluation of inflammatory and destructive changes in PsA hands, which was developed by the international OMERACT MRI in inflammatory arthritis group. MRI definitions of important pathologies in peripheral PsA and suggestions concerning appropriate MRI sequences for use in PsA hands are also provided.

MRI in early rheumatoid arthritis: synovitis and bone marrow oedema are independent predictors of subsequent radiographic progression

Objectives To determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in patients with early rheumatoid arthritis (RA). Methods 55 patients with RA with disease duration <1 year participated in this 3-year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months by swollen and tender joint count, disease activity score based on 28-joint count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as conventional x-rays of the hands and wrists. Results All measures of inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI bone marrow oedema were independent predictors of 3-year radiographic progression adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year cumulative measures of MRI synovitis and bone marrow oedema provided an improved explanation of variation (adjusted R2) in radiographic change compared with the baseline MRI values (adjusted R2=0.32 and 0.20 vs 0.11 and 0.04, respectively). Conclusions Both baseline and 1-year cumulative measures of MRI synovitis and bone marrow oedema independently predicted 3-year radiographic progression. These results confirm that MRI synovitis and MRI bone marrow oedema precede radiographic progression in patients with early RA.

Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort

Objectives One goal of remission in rheumatoid arthritis (RA) is to halt joint damage. The authors assessed the progression of radiographic joint damage among RA patients in remission by the new ACR/EULAR criteria (Boolean approach) compared with remission thresholds for the simplified disease activity index (SDAI), clinical disease activity index (CDAI) and disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) in an observational cohort, and evaluated the relationship between time in remission and radiographic joint damage. Methods 535 RA patients underwent physical examination and laboratory assessment at baseline, 1 and 2 years. Radiographs at baseline and 2 years were scored by the van der Heijde modified Sharp score (TSS). Positive likelihood ratios for a good radiographic outcome (change in TSS <1 unit/year) were calculated for each of the remission criteria. Radiographic progression was compared between patients in remission at none, one, two and three visits by χ2 goodness of fit statistics. Results 20% of patients in ACR/EULAR remission at baseline had radiographic progression, 24% in SDAI remission, 19% in CDAI remission and 30% of patients in DAS28–CRP remission. The positive likelihood ratio for good radiographic outcome was 2.6 for ACR/EULAR criteria, 2.1 for SDAI, 2.8 for CDAI and.1.5 for DAS28–CRP. Reduced radiographic progression was observed for patients with an increasing number of visits in remission (p<0.003 for all criteria, χ2 goodness of fit statistics). Conclusions Patients with RA in remission by any established criteria can experience radiographic progression. An increased number of visits in remission was associated with reduced radiographic damage.

Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study

Objectives: To describe a novel scoring system for the assessment of tenosynovitis by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis, and assess its intra- and inter-reader reliability in a multireader, longitudinal setting. Methods: Flexor and extensor tenosynovitis were evaluated at the level of the wrist in 10 different anatomical areas, graded semi-quantitatively from grade 0 to 3 (total score 0–30), based on the maximum width of post-contrast enhancement within each anatomical area on axial T1-weighted MR images. Ten sets of baseline and 1-year follow-up MR images of the wrists of patients with rheumatoid arthritis with early and established disease were scored independently by four readers twice on 2 consecutive days. Intra- and inter-reader agreements were evaluated. Results: The intrareader intraclass correlation coefficients (ICCs) were high for status scores (median ICCs 0.84–0.88) and slightly lower for change score (0.74). The smallest detectable difference (SDD) in % of the maximum score was 11.2–11.5% for status scores and 13.3% for change scores. Inter-reader single-measure ICCs were acceptable for both status scores (median 0.73–0.74) and change scores (0.67), while average-measures ICCs were very high for both status and change score (all ⩾0.94). The median scoring time per patient (baseline and follow-up images) was 7 min (range 3–10). Conclusions: The introduced tenosynovitis scoring system demonstrates a high degree of multireader reliability, is feasible, and may be used as an adjuvant to the existing OMERACT RAMRIS score, allowing improved quantification of inflammatory soft tissue changes in patients with rheumatoid arthritis.

Monitoring anti-TNFα treatment in rheumatoid arthritis: responsiveness of magnetic resonance imaging and ultrasonography of the dominant wrist joint compared with conventional measures of disease activity and structural damage

Objectives: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor α (TNFα). Methods: A cohort of patients with RA (N = 36, median age 53 years, disease duration 7.6 years and disease activity score (DAS28) 5.7) was evaluated by core measures of disease activity, US (one wrist), MRI (one wrist) and conventional radiography (CR, both hands and wrists) at initiation of treatment with anti-TNFα agents and after 3, 6 and 12 months. Responsiveness was assessed by standardised response means (SRM). Accepted thresholds were applied to classify responsiveness as trivial, low, moderate or good. Results: MRI synovitis (SRM between −0.79 and −0.92) and the MRI total inflammation score comprising synovitis, tenosynovitis and bone marrow oedema (SRM between −1.05 and −1.24) were highly responsive. Moderate to high responsiveness was found for MRI tenosynovitis and bone marrow oedema, all the composite indices (DAS28, simplified disease activity index (SDAI) and clinical disease activity index (CDAI)) and the 28-swollen joint count. US displayed low to moderate responsiveness. The MRI erosion score displayed low responsiveness but was more responsive than CR measures at 3 and 6 months follow-up. MRI and CR measures of annual progression rates of damage performed similarly and were highly responsive. Conclusions: The most responsive measure of inflammation when evaluating anti-TNFα medication was a composite measure comprising MRI synovitis, tenosynovitis and bone marrow oedema, and this may be a promising outcome measure in clinical studies.