Indistinguishability of Identical Bosons from a Quantum Information Theory Perspective.

Using tools from quantum information theory, we present a general theory of indistinguishability of identical bosons in experiments consisting of passive linear optics followed by particle number detection. Our results do neither rely on additional assumptions on the input state of the interferometer, such as, for instance, a fixed mode occupation, nor on any assumption on the degrees of freedom that potentially make the particles distinguishable. We identify the expectation value of the projector onto the N-particle symmetric subspace as an operationally meaningful measure of indistinguishability, and derive tight lower bounds on it that can be efficiently measured in experiments. Moreover, we present a consistent definition of perfect distinguishability and characterize the corresponding set of states. In particular, we show that these states are diagonal in the computational basis up to a permutationally invariant unitary. Moreover, we find that convex combinations of states that describe partially distinguishable and perfectly indistinguishable particles can lead to perfect distinguishability, which itself is not preserved under convex combinations.

Diagnostic Accuracy of a Mobile AI-Based Symptom Checker and a Web-Based Self-Referral Tool in Rheumatology: Multicenter Randomized Controlled Trial.

BACKGROUND: The diagnosis of inflammatory rheumatic diseases (IRDs) is often delayed due to unspecific symptoms and a shortage of rheumatologists. Digital diagnostic decision support systems (DDSSs) have the potential to expedite diagnosis and help patients navigate the health care system more efficiently. OBJECTIVE: The aim of this study was to assess the diagnostic accuracy of a mobile artificial intelligence (AI)-based symptom checker (Ada) and a web-based self-referral tool (Rheport) regarding IRDs. METHODS: A prospective, multicenter, open-label, crossover randomized controlled trial was conducted with patients newly presenting to 3 rheumatology centers. Participants were randomly assigned to complete a symptom assessment using either Ada or Rheport. The primary outcome was the correct identification of IRDs by the DDSSs, defined as the presence of any IRD in the list of suggested diagnoses by Ada or achieving a prespecified threshold score with Rheport. The gold standard was the diagnosis made by rheumatologists. RESULTS: A total of 600 patients were included, among whom 214 (35.7%) were diagnosed with an IRD. Most frequent IRD was rheumatoid arthritis with 69 (11.5%) patients. Rheport's disease suggestion and Ada's top 1 (D1) and top 5 (D5) disease suggestions demonstrated overall diagnostic accuracies of 52%, 63%, and 58%, respectively, for IRDs. Rheport showed a sensitivity of 62% and a specificity of 47% for IRDs. Ada's D1 and D5 disease suggestions showed a sensitivity of 52% and 66%, respectively, and a specificity of 68% and 54%, respectively, concerning IRDs. Ada's diagnostic accuracy regarding individual diagnoses was heterogenous, and Ada performed considerably better in identifying rheumatoid arthritis in comparison to other diagnoses (D1: 42%; D5: 64%). The Cohen κ statistic of Rheport for agreement on any rheumatic disease diagnosis with Ada D1 was 0.15 (95% CI 0.08-0.18) and with Ada D5 was 0.08 (95% CI 0.00-0.16), indicating poor agreement for the presence of any rheumatic disease between the 2 DDSSs. CONCLUSIONS: To our knowledge, this is the largest comparative DDSS trial with actual use of DDSSs by patients. The diagnostic accuracies of both DDSSs for IRDs were not promising in this high-prevalence patient population. DDSSs may lead to a misuse of scarce health care resources. Our results underscore the need for stringent regulation and drastic improvements to ensure the safety and efficacy of DDSSs. TRIAL REGISTRATION: German Register of Clinical Trials DRKS00017642; https://drks.de/search/en/trial/DRKS00017642.

Clinical Application of Ultrahigh-Field-Strength Wrist MRI: A Multireader 3-T and 7-T Comparison Study.

Background Ultrahigh-field-strength MRI at 7 T may permit superior visualization of noninflammatory wrist pathologic conditions, particularly due to its high signal-to-noise ratio compared with the clinical standard of 3 T, but direct comparison studies are lacking. Purpose To compare the subjective image quality of 3-T and 7-T ultrahigh-field-strength wrist MRI through semiquantitative scoring of multiple joint tissues in a multireader study. Materials and Methods In this prospective study, healthy controls and participants with chronic wrist pain underwent 3-T and 7-T MRI (coronal T1-weighted turbo spin-echo [TSE], coronal fat-suppressed proton-density [PD]-weighted TSE, transversal T2-weighted TSE) on the same day, from July 2018 to June 2019. Images were scored by seven musculoskeletal radiologists. The overall image quality, presence of artifacts, homogeneity of fat suppression, and visualization of cartilage, the triangular fibrocartilage complex (TFCC), and scapholunate and lunotriquetral ligaments were semiquantitatively assessed. Pairwise differences between 3 T and 7 T were assessed using the Wilcoxon signed-rank test. Interreader reliability was determined using the Fleiss kappa. Results In total, 25 healthy controls (mean age, 25 years ± 4 [SD]; 13 women) and 25 participants with chronic wrist pain (mean age, 39 years ± 16; 14 men) were included. Overall image quality (P = .002) and less presence of artifacts at PD-weighted fat-suppressed MRI were superior at 7 T. T1- and T2-weighted MRI were superior at 3 T (both P < .001), as was fat suppression (P < .001). Visualization of cartilage was superior at 7 T (P < .001), while visualization of the TFCC (P < .001) and scapholunate (P = .048) and lunotriquetral (P = .04) ligaments was superior at 3 T. Interreader reliability showed slight to substantial agreement for the detected pathologic conditions (κ = 0.20-0.64). Conclusion A 7-T MRI of the wrist had potential advantages over 3-T MRI, particularly in cartilage assessment. However, superiority was not shown for all parameters; for example, visualization of the triangular fibrocartilage complex and wrist ligaments was superior at 3 T. © RSNA, 2023 Supplemental material is available for this article.

Preferences for preventive treatments for rheumatoid arthritis: discrete choice survey in the UK, Germany and Romania.

OBJECTIVE: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. METHODS: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit-risk trade-offs and predicted treatment uptake was subsequently calculated. RESULTS: Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. CONCLUSION: Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

Impairment in cognitive function in patients with axial spondyloarthritis and psoriatic arthritis.

Spondyloarthritis may contribute to deficits in cognition. The objective of this study was to compare cognitive abilities in patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) with matched reference groups. This investigator-initiated, cross-sectional, exploratory study of adults with axSpA or PsA was conducted at two German rheumatology centres (November 2018-September 2019). All data on patient and disease characteristics and cognitive abilities were collected at a single visit. Cognitive function was assessed by the previously validated Memory and Attention Test subscores of selective attention, episodic working memory, and episodic short-term memory and compared with subscores from healthy age-, sex-, and education-matched reference subjects. The mean patient age was 51.1 and 55.8 years in the axSpA (n = 101) and PsA (n = 117) groups, respectively, and mean symptom duration was 13.7 and 10.3 years. Compared with matched reference subjects, axSpA and PsA patients showed significant impairments in selective attention (mean difference of -6.5 and -4.5, respectively, on a 45-point scale; P < 0.001 for both) and no significant differences in episodic working memory. The PsA cohort, but not the axSpA cohort, had significantly better episodic short-term memory subscores compared with matched reference subjects (mean change of 2.0 on a 15-point scale; P < 0.001). Explorative subgroup analyses were unable to identify factors influencing cognitive changes, including disease activity, pain, and function, but may have been underpowered. We conclude that impairments in selective attention may impact the ability of axSpA and PsA patients to process information. These findings warrant additional studies, including longitudinal analyses, in patients with spondyloarthritis.

A Real-World Rheumatology Registry and Research Consortium: The German RheumaDatenRhePort (RHADAR) Registry.

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner.

Eosinophils are not essential for maintenance of murine plasma cells in the bone marrow.

Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. Contrary to our expectations and the currently prevailing paradigm, we found that eosinophils are fully dispensable for the survival of murine bone marrow plasma cells and accordingly do not contribute to antibody production and autoantibody-mediated disease. Littermate wild type and eosinophil-deficient ΔdblGATA-1 animals showed similar numbers and frequencies of plasma cells and did not differ in steady state levels of immunoglobulins or their ability to raise antigen-specific antibody responses. Eosinophils were likewise dispensable for autoantibody production or autoantibody-induced disease in a mouse model of systemic lupus erythematosus. Our findings thus argue against a role of eosinophils during the maintenance of the plasma cell pool and challenge the hitherto postulated concept of an eosinophil-sustained bone marrow niche.

The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET). METHODS: Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT. RESULTS: 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still's disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001). CONCLUSION: 18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures.

OBJECTIVES: Bone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness. METHODS: Micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone based on high-resolution peripheral quantitative CT data from the distal radius of anti-citrullinated protein antibody (ACPA)-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC). In addition, total, trabecular and cortical bone densities as well as microstructural parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its relation to prevalent fractures. RESULTS: 276 individuals were analysed. Failure load and stiffness (both P<0.001) of bone were decreased in RA+, but not RA-, compared with HC. Lower bone strength affected both female and male patients with RA+, was related to longer disease duration and significantly (stiffness P=0.020; failure load P=0.012) associated with the occurrence of osteoporotic fractures. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (P=0.007) and sex (P<0.001) were independently associated with reduced biomechanical properties of bone in RA. CONCLUSION: In summary, µFEA showed that bone strength is significantly decreased in RA+ and associated with fractures.

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries.

Objective: To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods: We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. Results: A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion: Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original.

Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs.

OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. RESULTS: Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. CONCLUSIONS: The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy. TRIAL REGISTRATION NUMBER: 2009-015740-42; Results.

Type 2 innate lymphoid cell counts are increased in patients with systemic sclerosis and correlate with the extent of fibrosis.

OBJECTIVE: Type 2 innate lymphoid cells (ILC2s), a recently identified population of lymphoid cells lacking lineage-specific receptors, promote type 2 immunity and tissue remodelling. However, the contributive role of ILC2s in the pathogenesis of systemic sclerosis (SSc) is unknown. We aimed to evaluate the levels and correlations with fibrotic manifestations in SSc. METHODS: 69 patients with SSc and 47 healthy controls were included. Blood samples and skin sections were analysed by flow cytometry and immunohistochemically by staining two complementary panels of markers. RESULTS: Dermal and circulating ILC2s were significantly elevated in patients with SSc compared with controls. Dermal, but not circulating ILC2s were activated. Stratification of the SSc population in patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) demonstrated increased levels of ILC2s in both subgroups with significantly higher frequencies in dcSSc compared with lcSSc. Moreover, dermal and circulating ILC2 counts correlated closely with the modified Rodnan skin score and with the presence of pulmonary fibrosis. CONCLUSIONS: ILC2 counts are elevated in patients with SSc and correlate with the extent of skin fibrosis and the presence of interstitial lung disease providing compelling evidence for profibrotic effect of ILC2s in SSc.

Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis.

OBJECTIVES: To search for structural bone changes in the joints of psoriasis patients without psoriatic arthritis (PsA). METHODS: 55 psoriasis patients without any current or past symptoms of arthritis or enthesitis and 47 healthy controls were examined by high-resolution peripheral quantitative CT scans of the metacarpophalangeal joints. Number, size and exact localisation of erosions and enthesiophytes were recorded by analysing axial scans of the metacarpal heads and phalangeal bases and were confirmed in additional coronal and/or sagittal sections. In addition, we collected demographic and clinical data including subtype, duration and severity of psoriasis. RESULTS: Psoriasis patients showed a larger and significantly increased number of enthesiophytes (total number 306; mean±SD/patient 5.62±3.30) compared with healthy controls (total number 138; mean±SD/patient 3.04±1.81, p<0.001). Enthesiophytes were typically found at the dorsal and palmar sides of the metacarpal heads where functional entheses related to extensor and flexor tendons are localised. Bone erosions were rare and not significantly different between psoriasis patients and healthy controls. If present, erosions were almost exclusively found at the radial side of the second metacarpal head in both psoriasis patients and healthy controls. CONCLUSIONS: Psoriasis patients without PsA show substantial signs of enthesiophyte formation compared with healthy controls. These changes represent new bone formation at mechanically exposed sites of the joint and substantiate the concept of the existence of a 'Deep Koebner Phenomenon' at enthesial sites in psoriasis patients.

Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis.

OBJECTIVES: To search for subclinical inflammatory joint disease in patients with psoriasis without psoriatic arthritis (PsA), and to determine whether such changes are associated with the later development of PsA. METHODS: Eighty-five subjects without arthritis (55 with psoriasis and 30 healthy controls) received high field MRI of the hand. MRI scans were scored for synovitis, osteitis, tenosynovitis and periarticular inflammation according to the PsAMRIS method. Patients with psoriasis additionally received complete clinical investigation, high-resolution peripheral quantitative CT for detecting erosions and enthesiophytes and were followed up for at least 1 year for the development of PsA. RESULTS: 47% of patients with psoriasis showed at least one inflammatory lesion on MRI. Synovitis was the most prevalent inflammatory lesion (38%), while osteitis (11%), tenosynovitis (4%) and periarticular inflammation (4%) were less frequent. The mean (±SD) PsAMRIS synovitis score was 3.0±2.5 units. Enthesiophytes and bone erosions were not different between patients with psoriasis with or without inflammatory MRI changes. The risk for developing PsA was as high as 60% if patients had subclinical synovitis and symptoms related to arthralgia, but only 13% if patients had normal MRIs and did not report arthralgia. CONCLUSIONS: Prevalence of subclinical inflammatory lesions is high in patients with cutaneous psoriasis. Arthralgia in conjunction with MRI synovitis constitutes a high-risk constellation for the development of PsA.

Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study.

OBJECTIVE: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. METHODS: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. RESULTS: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). CONCLUSIONS: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. TRIAL REGISTRATION NUMBER: 2009-015740-42.

Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment.

OBJECTIVE: To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. METHODS: MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. RESULTS: Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). CONCLUSIONS: MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. TRIAL REGISTRATION NUMBER: EudraCT 2009-015740-42.

Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA.

OBJECTIVE: To determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis (RA) METHODS: 242 patients with RA received high-resolution peripheral quantitative CT (HR-pQCT) scans of the metacarpophalangeal joints. Demographic and disease-specific parameters including ACPA and RF levels were recorded from all patients. Erosion numbers and their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and 4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases). The volume of erosions was calculated by a semiellipsoid formula. RESULTS: Of the 238 patients, 112 patients showed RF and ACPAs (ACPAs+RF+), 28 only RF (RF+), 29 only ACPAs (ACPA+) and 69 were antibody negative (NEG). Erosion number and size were highest in RF+ACPAs+ patient group with significant differences compared with NEG patients with respect to erosion number (p=0.001) and to ACPA-negative patients with respect to erosion size (p<0.001). Results maintained significance in a linear mixed model showing ACPAs+RF+ status and disease duration being associated with higher number (p=0.017 and p=0.005, respectively), and larger size (p=0.014 and p=0.013, respectively) of bone erosions. Furthermore, erosion size was influenced by the presence and titre of RF only in ACPA-positive patients with RA but not in ACPA-negative patients. CONCLUSIONS: ACPAs and RF show an additive effect on erosion number and erosion size. Concomitant presence of ACPAs and RF is associated with higher erosive disease burden in patients with RA. Furthermore, RF influences erosion size only in ACPA-positive but not in ACPA-negative patients.

High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission.

OBJECTIVE: To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. METHODS: Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months. Demographic, disease-specific and ultrasound parameters were assessed at baseline. DMARDs (traditional or biologic) were discontinued at the initial visit, and patients were followed for a maximum of 6 months for recurrence of disease. RESULTS: 26 patients (methotrexate monotherapy: N=14; tumour necrosis factor inhibitors: N=12) with a mean age of 55.2 years, absence of musculoskeletal symptoms and minimal skin disease (mean Psoriasis Area Severity Index (PASI): 0.21) were enrolled. Incidence of recurrence of disease was high (N=20, 76.9%) and occurred rapidly (74.50±51.72 days) after treatment discontinuation. Male PsA patients were significantly more likely to lose remission. Long disease duration, more severe skin involvement and the presence of synovial hypertrophy by ultrasonographic examination at baseline decreased the likelihood for drug-free remission. Reinitiation of DMARDs promptly restored remission in all PsA patients with recurrence of disease. CONCLUSIONS: This study shows that the chance to reach drug-free remission in PsA patients is low. Discontinuation of DMARD therapy cannot be recommended in patients with PsA.

A comparative analysis of magnetic resonance imaging and high-resolution peripheral quantitative computed tomography of the hand for the detection of erosion repair in rheumatoid arthritis.

OBJECTIVES: To investigate whether MRI allows the detection of osteosclerosis as a sign of repair of bone erosions compared with high-resolution peripheral quantitative computed tomography (HR-pQCT) as a reference and whether the presence of osteosclerosis on HR-pQCT is linked to synovitis and osteitis on MRI. METHODS: A total of 103 RA patients underwent HR-pQCT and MRI of the dominant hand. The presence and size of erosions and the presence and extent (grades 0-2) of osteosclerosis were assessed by both imaging modalities, focusing on MCP 2 and 3 and wrist joints. By MRI, the presence and grading of osteitis and synovitis were assessed according to the Rheumatoid Arthritis MRI Score (RAMRIS). RESULTS: Parallel evaluation was feasible by both modalities on 126 bone erosions. Signs of osteosclerosis were found on 87 erosions by HR-pQCT and on 22 by MRI. False-positive results (MRI(+)CT(-)) accounted for 3%, while false-negative results (MRI(-)CT(+)) accounted for 76%. MRI sensitivity for the detection of osteosclerosis was 24% and specificity was 97%. The semi-quantitative scoring of osteosclerosis was reliable between MRI and HR-pQCT [intraclass correlation coefficient 0.917 (95% CI 0.884, 0.941), P < 0.001]. The presence of osteosclerosis on HR-pQCT showed a trend towards an inverse relationship to the occurrence and extent of osteitis on MRI [χ(2)(1) = 3.285; ϕ coefficient = -0.124; P = 0.070] but not to synovitis [χ(2)(1) = 0.039; ϕ coefficient = -0.14; P = 0.844]. CONCLUSION: MRI can only rarely detect osteosclerosis associated with bone erosions in RA. Indeed, the sensitivity compared with HR-pQCT is limited, while the specificity is high. The presence of osteitis makes osteosclerosis more unlikely, whereas the presence of synovitis is not related to osteosclerosis.

Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity.

OBJECTIVE: To investigate whether trabecular and cortical bone structure differ between patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). So far, no study has performed a detailed comparative analysis of bone structure in patients with RA and PsA. METHODS: 110 patients (60 RA, 50 PsA) received high-resolution peripheral quantitative CT of the distal radius. Demographic and disease-specific parameters including anti-rheumatic treatment, bone erosion status and previous fractures were recorded. RESULTS: RA and PsA patients were comparable in age, gender, body mass index, disease duration, disease activity, functional status, antirheumatic treatment and bone erosion status. No significant differences were found for volumetric bone mineral density (BMD), including total BMD (300±77 vs 316±62 mgHA/cm(3)), trabecular BMD (152±46 vs 165±40 mgHA/cm(3)) and cortical BMD (787±113 vs 818±76 mgHA/cm(3)) when comparing RA patients to PsA patients, respectively. However, in contrast to seronegative RA, seropositive RA showed significantly reduced trabecular BMD (p=0.007), bone volume per tissue volume (p=0.007) and trabecular number (p=0.044), as well as a strong trend towards higher trabecular inhomogeneity compared to PsA patients. In the regression analysis, higher age, female gender and presence of autoantibodies were independently associated with trabecular bone loss. CONCLUSIONS: Seropositive RA exhibits more profound changes in trabecular bone architecture than seronegative RA or PsA. The data support the concept that seropositive RA is a disease entity that is distinct from seronegative RA and PsA.