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Objective There is growing interest in the early identification of patients with axial PsA (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. Methods The dermatologist-centred screening (DCS) questionnaire was administrated by dermatologists to consecutive patients fulfilling the inclusion criteria [(i) age ≥18 years and (ii) clinical diagnosis of psoriasis made by a dermatologist] to identify patients eligible (affirmative answers 1–3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic and imaging data were collected from all referred patients. Results Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months and 140 (53%) reporting back pain onset before the age of 45 years. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients. Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with psoriasis without PsA. Conclusion The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA. [ABSTRACT FROM AUTHOR]

Objectives Myocarditis is an overlooked manifestation of anti-synthetase syndrome (ASS). Our study describes the clinical and instrumental features of ASS myocarditis and evaluates the performance of cardiac MRI (CMRI) with mapping techniques in assisting diagnosis of ASS myocarditis. Methods Data from patients with ASS were retrospectively analysed. CMRI data for patients diagnosed with myocarditis, including late gadolinium enhancement (LGE), T2 ratio, T1 mapping, extracellular volume (ECV) and T2 mapping, were reviewed. Myocarditis was defined by the presence of symptoms and/or signs suggestive for heart involvement, including increased high-sensitive troponin T (hs-TnT) and/or N-terminal pro-brain natriuretic peptide (NT-proBNP), and at least an instrumental abnormality. The clinical features of patients with ASS with and without myocarditis were compared. A P -value of <0.05 was considered statistically significant. Results Among a cohort of 43 patients with ASS [median age 58 (48.0–66.0) years; females 74.4%; anti-Jo1 53.5%], 13 (30%) were diagnosed with myocarditis. In 54% of those 13 patients, myocarditis was diagnosed at clinical onset. All patients with ASS with myocarditis had at least one CMRI abnormality: increased ECV in all cases, presence of LGE in 91%, and increased T1 and T2 mapping in 91%. The 2009 Lake Louise criteria (LLC) were satisfied by 6 patients, and the 2018 LLC by 10 patients. With the updated LLC, the sensitivity for myocarditis improved from 54.6% to 91.0%. Patients with ASS with myocarditis were more frequently males (53% vs 13%; P  = 0.009) with fever (69% vs 17%; P  = 0.001), and had higher hs-TnT [88.0 (23.55–311.5) vs 9.80 (5.0–23.0) ng/l; P  < 0.001], NT-proBNP [525.5 (243.5–1575.25) vs 59.0 (32.0–165.5; P  = 0.013) pg/ml; P  = 0.013] and CRP [7.0 (1.7–15.75) vs 1.85 (0.5–2.86) mg/l; P  = 0.011] compared with those without myocarditis. Conclusion In ASS, myocarditis is frequent, even at clinical onset. Patients with ASS with myocarditis frequently presented with fever and increased CRP, suggesting the existence of an inflammatory phenotype. The use of novel CMRI mapping techniques may increase diagnostic sensitivity for myocarditis in ASS. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. Methods The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit–risk ratio according to the number of fulfilled critical eligibility criteria. Results Among 1984 RA patients, only 9–12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P  = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25–4.06; for ≥3 criteria vs 0). The incremental risk–benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. Conclusion Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Objective To describe the frequency of progressive pulmonary fibrosis (PPF) in an incident cohort of systemic sclerosis (SSc)-related interstitial lung disease (ILD) and its impact on survival. Methods Incident ILD was defined as the new development of characteristic fibrotic changes on chest HRCT scan. PPF was defined as per the 2022 American Thoracic Society. Determinants of PPF were identified using generalised estimating equations. Impact on survival was analysed using accelerated failure time regression modelling. Results Of our incident SSc-ILD cases, 38.8% (n  = 180) experienced PPF within a 12-month period after ILD diagnosis. Determinants of PPF included older age (OR 1.02, 95%CI 1.00–1.03, P  = 0.011), dcSSc (OR 1.54, 95% CI 1.06–2.25, P  = 0.024) and SSc-specific antibodies (anticentomere antibody OR 0.51, 95%CI 0.29–0.91, P  = 0.021 and anti-Scl-70 antibody OR 1.46, 95%CI 1.01–2.09, P  = 0.043). Raised CRP was numerically associated with PPF but did not reach statistical significance (OR 1.29, 95%CI 0.99–1.68, P  = 0.064) nor did GORD or dysphagia (OR 1.18, 95%CI 0.57–2.42, P  = 0.658 and OR 1.17, 95%CI 0.57–2.40, P  = 0.664, respectively). The presence of PPF significantly impacted survival in SSc-ILD (hazard ratio 2.66, 95%CI 1.59–4.41, P  < 0.001). Conclusions PPF occurred in a third of our incident SSc-ILD cohort; however, its occurrence was significantly associated with mortality indicating an at-risk group who may be suitable for earlier introduction of immunosuppressive and/or antifibrotic therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate whether serum Col 3–4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis. Methods A total of 788 early arthritis patients (<6 months of symptoms, 82% diagnosis of RA, 18% undifferentiated arthritis) from the prospective ESPOIR study were investigated. Progression was defined as an increase of 1 or 5 unit(s) in radiographic van der Heijde modified Sharp score between baseline and 1 or 5 years, respectively. Associations between baseline Col 3–4 and progression were assessed by logistic regression. Results Each standard deviation increase of baseline Col 3–4 levels was associated with an increased 5-yr total damage progression with an odds ratio (OR, 95% CI) of 1.51 (1.21, 1.88), which remained significant when DAS28, C-reactive protein and anti-citrullinated protein antibodies positivity were included in the model [OR (95% CI): 1.34 (1.01, 1.76)]. Further adjustment for bone erosion did not modify the association. Patients with both Col 3–4 in the highest quintile and bone erosion had a >2-fold higher risk of progression [OR (95% CI): 7.16 (2.31, 22)] than patients with either high Col 3–4 [2.91 (1.79, 4.73)] or bone erosion [2.36 (2.38, 3.70)] alone. Similar associations were observed for prediction of 12 months progression. Conclusions Increased serum Col 3–4 is associated with a higher risk of structural progression, independently of major risk factors. Col 3–4 may be useful in association with bone erosion to identify patients with early arthritis at higher risk. [ABSTRACT FROM AUTHOR]

Objectives We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. Methods Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR–OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. Results In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239–0.756, P  < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. Conclusion DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading. [ABSTRACT FROM AUTHOR]

Objective To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA. Methods A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis. Results After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures. Conclusion A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA. [ABSTRACT FROM AUTHOR]

Objectives To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. Methods This retrospective multicentre case–control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. Results A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10–60). The median age at diagnosis was 48 years (IQR 33–60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P  = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P  < 0.001), and rituximab (P  = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3–44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P  = 0.038]. Conclusion Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV. [ABSTRACT FROM AUTHOR]

Objective 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are unknown. Therefore, we studied the presence of residual disease activity according physician's opinion, patient's opinion and composite indices and compared them to the subsequent treatment decisions. Methods This cross-sectional multicentre study included 249 patients with a clinical diagnosis of axSpA ≥6 months. Remission and low disease activity according to the BASDAI (<1.9 and <3.5, respectively) and physician's and patient's opinion were assessed. Questionnaires included patient-reported outcomes and patients and physicians completed questions regarding treatment decisions. Results A total of 115/249 (46%) patients were in remission according to the physician and 37% (n  = 43) of these patients reached remission according to the BASDAI. In 51/83 (60%) of the patients with residual disease activity according to the physician and a BASDAI >3.5 the treatment was left unchanged, either because of low disease activity as rated by the physician [ n  = 15 (29%)] or because of a combination of low disease activity with non-inflammatory complaints or comorbidities [ n  = 11 (25%)]. Retrospective treat-to-target evaluations showed that treatments were most frequently intensified in patients with arthritis or inflammatory back pain and less often in patients with other (non-inflammatory) musculoskeletal comorbidities. Conclusion This study shows that physicians do not always strictly apply treat-to-target in case of residual disease activity in axSpA. Usually, they accept low disease activity as satisfactory. [ABSTRACT FROM AUTHOR]

The article describes the case of a 75-year-old woman diagnosed with hypertension, chronic gastritis and insomnia and was treated with amlodipine, mosapride, suvorexant and clotiazepam. Topics include her diagnosis of drug-induced vanishing bile duct syndrome (VBDS), clinical characteristics of VBDS, and the need for clinicians to be aware that serious drug-induced liver injuries, including VBDS can occur after avacopan treatment for antineutrophilic cytoplasmic antibody-associated vasculitis.

Objectives There is no consensus on canakinumab treatment tapering and discontinuation strategies in colchicine-resistant FMF patients. In this study, we aimed to establish a treatment management and discontinuation protocol in paediatric FMF patients treated with canakinumab. Methods Fifty-eight FMF patients treated with canakinumab were included. Since 2020, we have applied a protocol based on our experience whereby canakinumab is administered monthly in the first 6 months, followed by bimonthly for 6 months, and a final period of every 3 months (for 6 months). The patients were divided into two groups: 2012–2019 (group A) and 2020–2022 (group B). Results In group A (n  = 33), the median duration of canakinumab treatment was 2.5 years [interquartile range (IQR) 1.9–3.7]. A total of 25 of 33 patients discontinued canakinumab after a median of 2.1 years (IQR 1.8–3.4). In two patients, canakinumab was restarted because of relapse. In group B (n  = 25), canakinumab was discontinued in 18 patients at the end of 18 months. After a median follow-up of 0.8 years (IQR 0.6–1.1), two patients had a relapse and canakinumab treatment was reinitiated. The remaining 16 patients still have clinically inactive disease and are receiving only colchicine. When we compared the characteristics between groups A and B, there were no significant differences regarding demographics, clinical features, and outcomes. Conclusion This is the largest study in the literature suggesting a protocol for discontinuing canakinumab in paediatric FMF patients. It was possible to discontinue canakinumab successfully in more than half of the patients in 18 months. Thus we suggest that this protocol can be used in paediatric FMF patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis. Methods Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated. Results At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P  < 0.01) and CRP level (r = 0.69, P  < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P  = 0.03), patients with higher ESR values (20 vs 49, P  = 0.02) and patients with active disease (62.5% vs 94.4%, P  < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P  < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up. Conclusion PETVAS showed good performance in predicting new lesions in Takayasu arteritis. [ABSTRACT FROM AUTHOR]

The author describes the case of a 42-year-old female patient who had been diagnosed with ankylosing spondylitis because she presented with chronic back pain, more in the lower spine, likely of the inflammatory type (IBP). He discusses the prevalence of items of potential relevance for a diagnosis of axial spondyloarthritis (axSpA), how mild disease would look like, and prediction of disease progression.

The article describes the case of a 44-year-old Caucasian woman with severe refractory antisynthetase syndrome (ASS). Topics discussed include typical manifestations of ASS in the patient, reason for initiating CAR-T cell treatment, and symptoms developed by the patient one week after CAR-T cell administration.

The article presents a case of relapsing polychondritis (RP) with pulmonary arteritis that was treated successfully with prednisolone (PSL), MTX and infliximab. Topics include medical history of the patient evaluated in the study, treatment given to the patient, and effectiveness of high-dose corticosteroids and biological agents for RP associated with large-vessel vasculitis (LVV).

Objective Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. Methods EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s. d. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s. d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. Results A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P  = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P  = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P  = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P  < 0.001). In the survival analysis, male sex was a predictor of mortality [OR 1.95 (95% CI 1.66, 2.28)]. Conclusions Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD. [ABSTRACT FROM AUTHOR]

The article presents a unique clinical case of a patient with skin lesions and bone pain. A 53-old man with no significant medical history developed pain initially localized to the right anterior tibial tuberosity, which extended to the entire tibia, including the contralateral tibia. It discusses the findings of computed tomography (CT) scan of the upper right tibia, an initial biopsy in favour of hypodermic neutrophil collection, and reason that the patient's initial biopsy was negative.

The article discusses the association of a novel gain-of-function missense variant in PLCG2 with autoinflammation and hypergammaglobulinemia in a case of a male patient with spina bifida. Topics mentioned include the levels of C-reactive protein and serum amyloid A, the results of histopathology of nasal septum and immunophenotyping of peripheral blood mononuclear cells, and the clinical features of B cell dysfunctions.

Objectives This study aimed to (i) investigate actual work participation in Belgian spondyloarthritis (SpA) patients compared with the general population, and (ii) identify determinants of work-related outcomes. Material and methods Adult SpA patients from the Ghent University Hospital based Be-GIANT cohort (fulfilling ASAS classification criteria) were cross-sectionally questioned on their socio-economic status and completed a Work Productivity and Activity Impairment questionnaire (May 2018 to May 2019). Results were compared with national and regional data on the general population using indirect standardization. Associations between clinical and job characteristics and work-related outcomes were analysed with logistic regression (having a paid job) and negative binomial hurdle models (sick leave and presenteeism, i.e. restrictions while at work). Results A total of 215/262 (82%) patients of working age (<65 y/o) had a paid job, corresponding to an age- and sex-adjusted employment ratio of 1.00 (95% CI 0.88, 1.14). Patients worked 39.6h (10.5h)/week, and 49% (95% CI 42, 56%) reported sick leave in the previous year, similar to the general population (39.7h/week, 42%). In total, 56% reported presenteeism of median (IQR) 10% (0–20%). In multivariate analysis, functional impairment (BASFI) and health-related quality of life (HRQoL, EuroQoL-VAS) were associated with each work-related outcome, while contextual factors (education, physically demanding job) were positively associated with, respectively, having a paid job and presenteeism. Clinical characteristics showed no independent association with any of these outcomes. Conclusions Evidence from this academic cohort study does not support a work participation gap between SpA patients and the general population, but confirms the role of physical function, overall HRQoL, and education or job type as risk factors for adverse work outcomes. [ABSTRACT FROM AUTHOR]

Objective To elucidate the prevalence of undiagnosed rheumatology-verified diagnosis of axial spondyloarthritis (RVD-axSpA) in patients attending routine secondary care IBD clinics with chronic back pain. Methods Screening questionnaires were sent to consecutive patients attending IBD clinics in a university teaching hospital. Patients fulling the eligibility criteria (gastroenterologist-verified diagnosis, 18–80 years old, biologic therapy naive, no previous diagnosis of axSpA); and a moderate diagnostic probability of axSpA [self-reported chronic back pain (CBP) >3 months, onset <45 years] were invited for rheumatology assessment. This included medical review, physical examination, patient reported outcome measures, human leucocyte antigen B27, C-reactive protein, pelvic radiograph and axSpA protocol magnetic resonance imaging. A diagnosis of RVD-axSpA was made by a panel of rheumatologists. Results Of the 470 patients approached, 91 had self-reported CBP >3 months, onset <45 years, of whom 82 were eligible for clinical assessment. The prevalence of undiagnosed RVD-axSpA in patients attending IBD clinics in a secondary care setting, with self-reported CBP, onset <45 years is estimated at 5% (95% CI 1.3, 12.0) with a mean symptom duration of 12 (s. d. 12.4) years. Conclusion There is a significant hidden disease burden of axSpA among IBD patients. Appropriate identification and referral from gastroenterology is needed to potentially shorten the delay to diagnosis and allow access to appropriate therapy. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. Methods Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex. Results For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)]. Conclusion Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA. [ABSTRACT FROM AUTHOR]

Objectives Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM. Methods We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications. Results There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++∼+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months. Conclusion These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis. [ABSTRACT FROM AUTHOR]

Objective Excessive cholesterol accumulation in macrophages is the pivotal step underlying atherosclerotic plaque formation. We here explore factors in the serum of patients with RA, and mechanisms through which they interact with and influence cholesterol loading capacity (CLC) of macrophages. Methods In a cross-sectional observational cohort of 104 patients with RA, CLC was measured as intracellular cholesterol content in human THP-1–derived macrophages after incubation with patient serum. Low-density lipoprotein (LDL) oxidation was measured in terms of oxidized phospholipids on apoB100-containing particles (oxPL-apoB100). Antibodies against oxidized LDL (anti-oxLDL), proprotein convertase subtilisin/Kexin type-9 (PCSK9) and high-sensitivity CRP were also quantified. All analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, obesity, total LDL, statin use, age at diagnosis, and anti-oxLDL IgM. Results OxPL-apoB100, anti-oxLDL IgG and PCSK9 were positively associated with CLC (all P  < 0.020). OxPL-apoB100 directly influenced CLC only in dual RF- and ACPA-positive patients [unstandardized b (95% bootstrap CI)=2.08 (0.38, 3.79)]. An indirect effect of oxPL-apoB100 on CLC through anti-oxLDL IgG increased, along with level of CRP [index of moderated mediation = 0.55 (0.05–1.17)]. CRP also moderated yet another indirect effect of oxPL-apoB100 on CLC through upregulation of PCSK9, but only among dual-seropositive patients [conditional indirect effect = 0.64 (0.13–1.30)]. Conclusion Oxidized LDL can directly influence CLC in dual-seropositive RA patients. Two additional and independent pathways—via anti-oxLDL IgG and PCSK9—may mediate the effects of oxPL-apoB100 on CLC, depending on CRP and seropositivity status. If externally validated, these findings may have clinical implications for cardiovascular risk prevention. [ABSTRACT FROM AUTHOR]

Objective To find indicators of disease severity and factors of early remission in patients with deficiency of adenosine deaminase 2 (DADA2). Methods We enrolled six DADA2 patients from six families. Direct sequencing of adenosine deaminase 2 gene (ADA2) was performed by Sanger analysis. A literature review was conducted for articles regarding paediatric DADA2. Results We found that more organs were involved in early-onset (≤1 year of age) than in late-onset (>1 year of age) DADA2 patients had high level inflammatory responses, such as elevated ESR, SF, serum amyloid A and CRP. Disease severity was not significantly different from missense and frameshift mutation. Early administration of TNF inhibitor might result in better remission and reduce recurrence. In the literature, four articles describing 51 paediatric DADA2 patients were identified. We also found that fever, stroke, peripheral nervous system involvement, hypogammaglobulinaemia and hypertension were more frequent in early onset DADA2 patients. Conclusion Early-onset DADA2 may be more severe. Early administration of TNF inhibitor can effectively reduce recurrence and quickly alleviate the disease. [ABSTRACT FROM AUTHOR]

Objective Mucosal initiated immune responses may be involved in the pathophysiology of RA. The most abundant immunoglobulin at mucosal surfaces is IgA, of which two subclasses exist: IgA1 and IgA2. IgA2 is mainly present at mucosal sites and has been ascribed pro-inflammatory properties. As IgA subclasses might provide insights into mucosal involvement and pro-inflammatory mechanisms, we investigated IgA responses in sera of RA patients. Methods In two cohorts of RA patients, the EAC and IMPROVED, total IgA1 and IgA2 were measured by ELISA. Furthermore, IgA subclass levels of RF and anti-citrullinated protein antibodies (anti-CCP2) were determined. The association of these IgA subclass levels with CRP and smoking was investigated. Results Total IgA1 and IgA2 were increased in RA patients compared with healthy donors in both cohorts. This increase was more pronounced in seropositive RA vs seronegative RA. For RF and anti-CCP2, both IgA1 and IgA2 could be detected. No strong associations were found between IgA subclasses (total, RF and anti-CCP2) and CRP. In smoking RA patients, a trend towards a selective increase in total IgA2 and RF IgA1 and IgA2 was observed. Conclusion RA patients have raised IgA1 and IgA2 levels. No shift towards IgA2 was observed, indicating that the increase in total IgA is not due to translocation of mucosal IgA into the bloodstream. However, mucosal inflammation might play a role, given the association between smoking and total IgA2 levels. Despite its pro-inflammatory properties, IgA2 does not associate strongly with pro-inflammatory markers in RA patients. [ABSTRACT FROM AUTHOR]

Objective To unravel disease impact in early RA by separately quantifying patient-reported (PRF), clinical (CF) and laboratory (LF) factors. We propose a new indicator, the discordance score (DS), for early identification and prediction of patient's unmet needs and of future achievement of sustained remission (SR) and RA-related quality of life (QoL). Methods Factor-scores obtained by factor analysis in the CareRA trial, allowed to compute DS, reflecting the difference between PRF and the mean of CF and LF. Improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time points per factor-score were calculated and compared between patients achieving/not achieving sustained (week 16–104) remission (DAS28CRP < 2.6) with ANOVA. Logistic and linear regressions were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16. Results PRF, CF and LF scores improved rapidly within 8 weeks. PRF improved 57%, CF 90% and LF 27%, in those achieving SR, compared with 32% (PRF: P  = 0.13), 77% (CF: P  < 0.001) and 9% (LF: P  = 0.36) in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF, respectively, compared with 33.2, 10.1 and 7.2 in participants not achieving SR (P  < 0.001 for all). Early discordance was associated with later factor scores, QoL and self-efficacy. Conclusions All factor scores improved rapidly, especially in patients achieving sustained remission. Patient-reported burden improved less. Discordance scores could help predicting the need for additional non-pharmacological interventions to achieve sustained remission and decrease disease impact. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the association between genetically predicted Interleukin-6 receptor inhibitor (IL-6Ri) and sarcoidosic risk. Topics include procedure made by the researchers to genetically mimic the effect of IL-6Ri, reason for choosing C-reactive protein (CRP) as the biomarker, and strength and limitation of the study.

Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. Methods Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start). Results Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P  < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P  < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis. Conclusion This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy. [ABSTRACT FROM AUTHOR]

Objective To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials. Methods Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score (<2 or ≥2). Results In the COAST-V/W integrated dataset (N  = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P  < 0.05; 35% IXEQ2W, P  < 0.01 vs 12% PBO), CRP >5 mg/l (39% IXEQ4W, P  < 0.001; 43% IXEQ2W, P  < 0.001 vs 17% PBO), SPARCC MRI spine score <2 (40% IXEQ4W P  < 0.01, 52% IXEQ2W P  < 0.001 vs 16% PBO), and SPARCC MRI spine score ≥2 (44% IXEQ4W P  < 0.001, 47% IXEQ2W P  < 0.001 vs 19% PBO). ASAS40 response was observed with CRP ≤5 mg/l and SPARCC MRI spine score <2 with IXEQ4W (29%) and was significant with IXEQ2W (48%; P  < 0.05) vs PBO (13%). Conclusion Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798 [ABSTRACT FROM AUTHOR]

Objectives To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. Methods Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. Results We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n  = 33, 80.5%) and non-parenchymal (n  = 17, 41.5%). First BTs used were infliximab (n  = 19), adalimumab (n  = 14), golimumab (n  = 3), tocilizumab (n  = 3) and etanercept (n  = 2). After 6 months of BT, neurological remission was complete (n  = 23, 56.1%), partial (n  = 15, 37.6%) and no response (n  = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30–60) mg/day at the initial visit to 5 (3.8–10) mg/day after 6 months (P  < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)–15.3 (11.9) mm/1st h, P  = 0.011] and median (IQR) C-reactive protein [1.4 (0.2–12.8) to 0.3 (0.1–3) mg/dl, P  = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n  = 16) or adverse events (AEs) (n  = 6) and discontinued due to complete prolonged remission (n  = 3) or severe AE (n  = 1). Serious AEs were observed in two patients under infliximab treatment. Conclusions BT appears to be effective and relatively safe in refractory NBD. [ABSTRACT FROM AUTHOR]

Objectives To characterize and clarify evidence as to whether the ectopic bone formations of DISH in patients with ossification of the posterior longitudinal ligament (OPLL) are caused by inflammatory or degenerative processes. Methods Whole-spine CT and serum high-sensitivity CRP (hs-CRP) levels were obtained from 182 cervical OPLL patients (DISH+, n  = 104; DISH−, n  = 78). In the DISH+ group, ectopic bone formations were categorized into Flat and Jaggy types, then further divided into three subgroups: group 1 (Jaggy-dominant pattern), group 2 (Equivalence of pattern) and group 3 (Flat-dominant pattern). Data were compared between the DISH+ and DISH− groups, and among the three subgroups. Results The upper thoracic spine was most affected by the Flat type, whereas the Jaggy type was more frequent in the middle and lower thoracic regions. There was no difference in hs-CRP levels between the DISH+ and DISH− groups. Among the three subgroups, hs-CRP levels in group 3 [mean (s. d.) 0.16 (0.09) mg/dl] were significantly higher than in group 1 [0.04 (0.02) mg/dl] and group 2 [0.08 (0.06) mg/dl]. Higher levels of hs-CRP were associated with a greater number of vertebral units with Flat-type formations (β  = 0.691 , P < 0.0001) and with a lesser number of vertebral units with Jaggy-type formations (β  = −0.147, P  = 0.036). Conclusion The Flat type in DISH might be caused by an inflammatory pathogenesis rather than a degenerative process presented in the Jaggy type. [ABSTRACT FROM AUTHOR]

The article describes the case of a Japanese baby boy with a birthweight of 2826 grams, delivered at 38 weeks of gestation by vacuum delivery, without any perinatal abnormalities. Topics discussed the boy's hospitalization from five days of age more than once a month for high fever and oral ulcers, his treatment based on a diagnosis of Bechet's disease, and conclusion on the effectiveness of thalidomide for treating refractory gastrointestinal lesions caused by A20 haploinsufficiency (HA20).

Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006–18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56–2.35)] and SGA [1.93 (1.45–2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52–7.55) for PTB and 3.90 (1.46–10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94–4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66–2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment. [ABSTRACT FROM AUTHOR]

Objective To compare body composition parameters in patients with long-standing JDM and controls and to explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQoL) and cardiometabolic measures. Methods We included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls in a cross-sectional study. Active and inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body DXA, inflammation by high-sensitivity CRP (hs-CRP) and cytokines, muscle strength by the eight-muscle manual muscle test, HRQoL by the 36-item Short Form Health Survey physical component score and cardiometabolic function by echocardiography (systolic and diastolic function) and serum lipids. Results DXA analyses revealed lower appendicular lean mass index (ALMI; reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and a higher android fat:gynoid fat (A:G) ratio (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 and hs-CRP). Lower ALMI was associated with reduced muscle strength, while higher BF% was associated with impaired HRQoL. Central fat distribution (higher A:G ratio) was associated with impaired cardiac function and unfavourable serum lipids. Conclusion Despite normal BMI, patients with JDM, especially those with active disease, had unfavourable body composition, which was associated with impaired HRQoL, muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM. [ABSTRACT FROM AUTHOR]

The article describes the case of an 89-year-old Caucasian female patient with tongue necrosis and complained of bilateral shoulder pain, headache, and visual impairment. Topics discussed include her c-reactive protein (CRP) levels, medication received by the patient, and clinical characteristics of tongue necrosis.

The article describes the case of a two-month-old girl with fever, maculopapular erythematous rash, irritability and rapid breathing. Topics discussed include findings on laboratory investigations, a clinical possibility of Kawasaki disease, and a spectrum of skin manifestations reported in patients with Kawasaki disease.

Objectives Identification of RA patients at a high risk of joint destruction remains challenging. The C-X-C motif chemokine 13 (CXCL13) has previously been suggested as a marker of disease activity in RA. Here, we investigate the potential of plasma CXCL13 as a marker of long-term radiographic status and progression. Methods CXCL13 was measured in plasma from treatment-naïve RA patients (n  = 158) with an 11-year follow-up. At baseline, clinical and biochemical DASs were obtained; among these CRP, ESR, DAS in 28 joints with CRP (DAS28CRP), number of swollen joints (SJC28) and radiographic status, evaluated by total Sharp score (TSS). Age- and gender-matched healthy controls (HCs) were included. Results CXCL13 was significantly increased at baseline and decreased during treatment; however, it was not reduced to the level in HCs. At baseline, CXCL13 was associated with both CRP and ESR, but not with other markers of disease activity. Baseline CXCL13 was correlated with both TSS and radiographic progression (ΔTSS) at 11 years. With an 89% probability, levels of CXCL13 above 85 pg/ml predicted the risk of a TSS of 5 or above, after 11 years of treatment. Compared with CRP, DAS28CRP, SJC28 and ACPA status, CXCL13 was superior in predicting 11-year joint destruction. Conclusion In early RA, one single measurement of plasma CXCL13 at baseline is superior to currently used clinical and serological disease markers in the prediction of long-term radiographic status and progression. [ABSTRACT FROM AUTHOR]

Objectives We investigated the effect of disease activity-guided dose optimization (DAGDO) of TNF inhibitor (TNFi) on disease activity and TNFi dose in PsA and axial spondyloarthritis (axSpA) patients with low disease activity (LDA). Methods A retrospective cohort study was conducted in PsA and axSpA patients doing well on TNFi and eligible for TNFi DAGDO. Three different treatment periods were defined: (i) full dose continuation period, (ii) TNFi DAGDO period, and (iii) period with stable TNFi dose after DAGDO. A mixed-model analysis was used to estimate mean Disease Activity Score 28-joint count CRP (DAS28-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) during these periods, and a mean percentage of the daily defined dose (%DDD) was calculated as secondary outcome. Results Three hundred and twenty-four patients (153 PsA and 171 axSpA) were included, with a mean of 6.5 DAS28-CRP and 6.4 BASDAI measurements and a median follow-up duration of 46 and 44 months, respectively. A corrected difference of 0.06 (95% CI: −0.09, 0.21) in mean DAS28-CRP was found for the TNFi DAGDO period and 0.03 (95% CI: −0.14, 0.20) for the period with stable TNFi dose, compared with full dose continuation period. Differences for BASDAI were 0.03 (95% CI: −0.21, 0.27) and 0.05 (95% CI: −0.24, 0.34), respectively. The mean %DDD for the three treatment periods was for PsA 108%, 62% and 78%, and for axSpA 108%, 62% and 72%, respectively. Conclusion DAGDO of TNFi reduces drug exposure and has no negative effects on disease activity in PsA and axSpA patients compared with full dose continuation. [ABSTRACT FROM AUTHOR]

Objectives The optimal treatment target in axial spondyloarthritis (axSpA) is remission; however, a consensual definition of remission is lacking. Our objective was to explore rheumatologists' perception of remission using vignette cases and a priority exercise. Methods A cross-sectional survey of rheumatologists' perceptions of remission in axSpA was performed in 2020 using (i) 36 vignette cases, with a single clinical picture and three varying parameters [axial pain (ranging from 2 to 5 on a 0–10 scale)], fatigue (2–8), and morning stiffness (<15 min, 30 min or 1 h), assessed as remission yes/no; and (ii) prioritization of elements to consider for remission from a list of 12 items: BASDAI, ASDAS, elements of BASDAI and ASDAS including CRP, NSAID use, extra-articular manifestations (EAMs), and other explanations of symptoms, e.g. fibromyalgia. Analyses were descriptive. Results Overall, 200 French rheumatologists participated in 2400 vignette evaluations. Of these, 463 (19%) were classified as remission. The six vignette cases representing 56% of all remission cases had <15 min duration of morning stiffness and axial pain ≤3/10, regardless of fatigue levels. Prioritized items for remission were: morning stiffness (75%), EAMs (75%), NSAID use (71%), axial pain (68%) and CRP (66%). Conclusions When conceptualizing remission in axSpA, rheumatologists took into account morning stiffness and axial pain as expected; the link between remission and fatigue was much weaker. Furthermore, rheumatologists also included EAMs and NSAID use in the concept of remission. Consensus is needed for definition of remission in axSpA. [ABSTRACT FROM AUTHOR]

Objective Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24. Methods The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons. Results This analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P  < 0.05) were observed in ethnicity, region, body mass index group, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, swollen joint count, CRP, CDAI and oral glucocorticoid use between these treatment groups. After adjusting for these differences in a mixed-effect model repeated measure, LS mean change from baseline for all assessments was similar between the treatment groups with overlapping CIs: CDAI, −28.79 vs −26.21; DAS28-CRP, −2.95 vs −2.81; CRP, −18.31 vs −16.46; Hb, 6.59 vs 8.09; Pain VAS, −33.62 vs −31.66; FACIT-Fatigue, 9.90 vs 10.24. Conclusion This analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41–113) of the randomized controlled CLUSTER trial. Methods During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than <35 mg/kg, ≥35 to <70 mg/kg or ≥70 mg/kg. Results Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events. Conclusion Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported. Trial registration NCT02059291. https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Objectives Little is known with certainty about the natural history of spinal disease progression in ankylosing spondylitis (AS). Our objective was to discover if there were distinct patterns of change in vertebral involvement over time and to study associated clinical factors. Methods Data were analysed from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) observational cohort. All patients met modified New York Criteria for AS and had ≥2 sets of radiographs scored by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by two independent readers between 2002 and 2017. Group-based trajectory modelling (GBTM) was used to classify patients into distinct groups of longitudinal mSASSS considering sociodemographic and clinical covariables. The optimal trajectory model and number of trajectories was selected using Nagin's Bayesian information criterion (BIC). Results A total of 561 patients with 1618 radiographs were analysed. The optimum number of trajectory groups identified was four (BIC −4062). These groups were subsequently categorized as: non-progressors (204 patients), late-progressors (147 patients), early-progressors (107 patients) and rapid-progressors (103 patients). Baseline predictors associated with higher spinal disease burden groups included: baseline mSASSS, male gender, longer disease duration, elevated CRP and smoking history. In addition, time-varying anti-TNF use per year was associated with decreased mSASSS progression only in the rapid-progressor group. Conclusions GBTM identified four distinct patterns of spinal disease progression in the PSOAS cohort. Male gender, longer disease duration, elevated CRP and smoking were associated with higher spinal disease groups. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns. [ABSTRACT FROM AUTHOR]

Objectives An elevated sFlt-1/PlGF ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with RA. We explored whether the sFlt-1/PlGFratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since SSZ has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether SSZ could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (P = 0.07 and P = 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r = −0.01 and r = −0.05, respectively). Four (2%) women with a sFlt-1/PlGF ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. SSZ users (n  = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-SSZ users (n  = 164, P = 0.91 and P = 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, SSZ use did not affect sFlt-1 or PlGF levels in this population. [ABSTRACT FROM AUTHOR]

The article describes a novel phenotype of the described vacuoles, E1 enzyme, X-linked, inflammatory somatic (VEXAS) syndrome. Topics discussed include evaluation for noted leucopenia, finding on subsequent high muscle magnetic resonance imaging (MRI), and myositis as a prominent presenting feature of the syndrome.

Background Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases. Methods In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described. Results A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n  = 4), unifocal (n  = 6), and enthesitis/synovitis/dactylitis (n  = 1). The mean duration of symptoms was 46 weeks (range 6–119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications Conclusions A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy. [ABSTRACT FROM AUTHOR]

Objective To explore global miRNA and transcriptomic profiling of monocytes from RA patients compared with healthy controls in order to predict which aberrantly expressed miRNA can negatively modulate inflammatory molecules. Methods Using next-generation sequencing, we have performed simultaneous global analysis of miRNA (miRNA-seq) and transcriptome (RNA-seq) of monocytes from RA patients and healthy controls. Global analysis of miRNA of SSc monocytes was also performed. Following differential analysis and negative correlation, miRNA–RNA pairs were selected. Results We found that 20 specific miRNA candidates are predicted to silence inflammatory mediators, out of 191 significantly changed miRNAs in RA monocytes. Based on the highest scoring in terms of negative correlation (r  = −0.97, P  = 1.75e–07, false discovery rate = 0.04) and the number of seeds in miRNA responsible for negative regulation, we selected miRNA-146b and its target gene anti-inflammatory retinoic acid receptor alpha (RARA). Similarly to next-generation sequencing, qPCR analysis also confirmed negative correlation between miRNA-146b and RARA expression (r  = −0.45, P  = 0.04). Additionally, miRNA-146b expression in RA monocytes significantly correlated with clinical parameters including DAS28 for RA with CRP (DAS28-CRP) and ESR (DAS28-ESR), whereas overexpression of miRNA-146b was able to functionally reduce RARA expression in the human monocytic cell line THP-1. Finally, circulating miRNA-146b expression in sera and SFs was significantly elevated in RA patients. Conclusions Overall, in this study we have identified a new miRNA-146b candidate that is predicted to negatively regulate the anti-inflammatory RARA transcript, whereas circulating miRNA-146b level can be used as a biomarker predicting pro-inflammatory RA progression and disease activity. [ABSTRACT FROM AUTHOR]

Objectives Environmental air pollution has been linked to the pathogenesis of RA. Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing. The objective of the present study was to determine the association between RA flares and air pollution. Methods We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. We compared the exposure to pollutants in the 30‐day and 60-day periods preceding an arthritic flare referent to the 30‐day and 60-day preceding a low-disease activity visit. Results The study included 888 patients with RA with 3396 follow-up visits; 13 636 daily air pollution records were retrieved. We found an exposure–response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels. Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/l. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare. Conclusions We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure. [ABSTRACT FROM AUTHOR]

Objective To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD). Methods We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature. Results KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s. d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s. d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s. d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients. Conclusion On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined. [ABSTRACT FROM AUTHOR]

Objectives To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. Methods AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Results Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724  (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10  (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88  (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457  (1298) ng/ml and 54.98  (48.67) mg/l, respectively]. Conclusion Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients. [ABSTRACT FROM AUTHOR]