Abstract Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815 .
Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PADAct) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PADAct were evaluated by Mann–Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test.Results: PADAct positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PADAct-positive were younger than PADAct-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.
The OMERACT RA MRI scoring system (RAMRIS) evaluates bone erosions, bone edema, and synovitis. The system is validated and increasingly used as an outcome measure in RA clinical trials. However, joint space narrowing (JSN), reflecting cartilage damage, is an important aspect of the joint damage in RA, and reliable assessment of this could constitute a useful additional outcome measure in RA clinical trials.
Objectives
The aim of the present OMERACT initiative was to validate the newly proposed MRI scoring system for JSN [1].
Methods
Fourteen RA patients’ and one healthy control’s 2nd-5th metacarpophalangeal joints (MCP2-5) and wrist on one hand were assessed for JSN on MRI and CT by three experienced readers. Images were read twice with different identification numbers for blinding.
Results
Patient demographics: 71% female, age median 61 years (range 31-78), disease duration 5 (1-20), 71% IgM rheumatoid factor positive, Sharp/van der Heijde X-ray scores: Total 75 (3-106), joint space narrowing 40 (1-70), erosion 27 (2-44)). On both MRI and CT, high intrareader (ICCs ≥0.91) and interreader (ICCs ≥0.89) reliability were found for total assessment of JSN (see table). The agreement was generally lower for MCP joints than the wrist, particularly for CT.
Conclusions
High intra- and interreader reliabilty was obtained by three readers assessing JSN on MRI and CT using the OMERACT JSN MRI scoring system. The score may be a useful outcome measure in RA clinical trials.
References
Østergaard M, et al.: Development and preliminary validation of a magnetic resonance imaging joint space narrowing score for use in rheumatoid arthritis: potential adjunct to the OMERACT RA MRI scoring system. J.Rheumatol. 2011;38:2045-50.
Synovitis in patients with rheumatoid arthritis (RA) may be scored semiquantitatively (0–3) for B-mode (BM) and power Doppler (PD) ultrasonography. The objective was to assess the reliability of BM and PD examinations with a novel ultrasonographic atlas as reference.
Methods
Representative ultrasound images (including scores 0–3) of BM and PD from 24 different joints were collected to develop an ultrasonographic atlas. Ten RA patients were assessed twice by five rheumatologists performing BM and PD scoring (0–3) of 16 joints bilaterally (metacarpophalangeal 1–5, wrist (radiocarpal, intercarpal, radioulnar), elbow, knee, talocrural and metatarsophalangeal 1–5), with the novel ultrasonographic atlas as a reference.
Results
The median (range) percentages of exact agreements for BM/PD assessments were 73.1 (70.3–80.6)/83.7 (76.7–87.6) and for close agreement 98.1 (96.2–99.7)/98.0 (96.8–98.4) with weighted κ values of median (range) 0.77 (0.70–0.83) for BM and 0.83 (0.73–0.86) for PD. The intrarater intraclass correlation coefficients (ICC) for BM/PD scores were 0.95 (0.93–0.99)/0.97 (0.95–0.99) and interrater ICC were 0.95 (0.86–0.99)/0.97 (0.94–1.00). Scoring of 32 joints was completed in median 15 min (range 12–20).
Conclusion
With the use of an ultrasonographic atlas as reference high intra and interrater reliability was found for BM and PD scoring. This novel atlas may be a useful resource in clinical practice and research.
The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials. The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period. The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events. Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC. ClinicalTrials.gov, number NCT02148640.
Abstract Introduction Prognosis in rheumatoid arthritis (RA) is difficult to assess. The aim of this study was to examine whether serum levels of a spectrum of cytokines were predictive of radiographic progression in early RA patients. Methods A total of 82 early RA patients (disease duration < 1 year) were followed for 12 months. Clinical assessments, X-rays of hands and magnetic resonance imaging (MRI) of the dominant wrist were assessed at baseline and after 3, 6 and 12 months. The X-rays were scored according to the van der Heijde modified Sharp score (vdHSS). Cytokine analyses were performed with multiplex technology. Associations between cytokines and radiographic progression were examined by logistic regression. Results In all, 49% of the patients developed radiographic progression. The median (interquartile range (IQR)) baseline eotaxin level (pg/ml) was significantly lower in patients with (193 (119 to 247)) than without progression (265 (166 to 360)). In the univariate logistic regression analyses, eotaxin was negatively associated to radiographic progression, and this association was maintained in the multivariate model with an odds ratio (OR) (95% confidence interval (CI)) for progression of 0.58 (0.41 to 0.82) per 50 pg/ml increase in eotaxin level. None of the other measured cytokines showed any association to radiographic progression. Conclusion This study raises the hypothesis that high serum levels of eotaxin predict less radiographic progression in early RA patients.
Objective. To develop and validate a magnetic resonance imaging (MRI) method of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA). Methods. Phase A: JSN was scored 0–4 on MR images of 5 RA patients and 3 controls at 15 wrist sites and 2nd–5th metacarpophalangeal (MCP) joints by 8 readers (7 once, one twice), using a preliminary scoring system. Phase B: Image review, discussion, and consensus on JSN definition, and revised scoring system. Phase C: MR images of 15 RA patients and 4 controls were scored using revised system by 5 readers (4 once, one twice), and results compared with radiographs [Sharp-van der Heijde (SvdH) method]. Results. Phase A: Intraobserver agreement: intraclass correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached on JSN definition (reduced joint space width compared to normal, as assessed in a slice perpendicular to the joint surface), and revised scoring system (0–4 at 17 wrist sites and 2nd–5th MCP; 0: none; 1: 1–33%; 2: 34–66%; 3: 67–99%; 4: ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was 0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar reliability and correlation with radiographic scores. Conclusion. An MRI scoring system of JSN in RA wrist and MCP joints was developed and showed construct validity and good intra- and interreader agreements. The system may, after further validation in longitudinal data sets, be useful as an outcome measure in RA.
This article updates the work and research priorities of the OMERACT working group on magnetic resonance imaging (MRI) in inflammatory arthritis, as presented to the OMERACT 8 meeting in Malta in May 2006. This work focused on testing the reliability of dedicated extremity MRI in rheumatoid arthritis and on the initial steps in the development of an MRI score for peripheral psoriatic arthritis.
