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Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotising vasculitis characterised by tissue and blood hypereosinophilia. Cardiac involvement has previously been identified as the most significant predictor of mortality.

Objective: To identify and characterise previously untreated patients with EGPA and their cardiac manifestations at disease onset.

Methods: A retrospective monocentre study was conducted on 103 patients. Upon patient presentation, detailed multidisciplinary physical evaluations and laboratory diagnostics were performed. Cardiac events were defined as EGPA-related abnormalities in ECG, echocardiography, cardiac MRI, invasive coronary angiography or cardiac histopathology.

Results: Cardiac manifestations were diagnosed in 36 of 103 patients with EGPA (35%). Patients with EGPA with cardiac involvement (EGPA-CI) exhibited typical symptoms of EGPA concomitant with elevated cardiac biomarkers. Pericarditis (77%), cardiomyopathy with cardiac failure (55%) and definite myocarditis (36%) were the most common diagnoses, which in some cases resulted in cardiogenic shock (14%) or cardiac arrest (6%). Vasospastic coronary arteries causing myocardial infarctions were identified as a life-threatening cardiac manifestation in 8% of patients with EGPA-CI. Overall, patients with EGPA-CI presented with significantly higher disease activity and worse prognosis, with elevated median eosinophilic count and C-reactive protein levels.

Conclusions: Cardiac involvement is a common initial manifestation of EGPA and is associated with elevated systemic disease activity. In addition to pericarditis and myocarditis, coronary vasospasms were identified as a rare and severe manifestation of EGPA that may mimic myocardial infarction. Consequently, at the early stage of disease, patients may present with advanced cardiac impairment, emphasising the necessity of prompt diagnostic and therapeutic intervention to positively affect prognosis.

The management of rheumatoid arthritis (RA) has significantly improved, but a substantial number of patients still experience persistent disease activity, leading to the concept of 'difficult-to-treat RA' (D2T RA). The European Alliance of Associations for Rheumatology (EULAR) has provided a pivotal definition for D2T RA to unify clinical approaches and research methods. This definition frames D2T RA as an umbrella term for a diverse group of patients with management challenges stemming from various factors, including biological resistance, patient experience, and clinical complexities. This framework is invaluable for a previously ill-defined population, but its real-life application highlights areas for ongoing consideration and potential refinement. Here, we discuss some of the strengths and limitations of the EULAR definition for D2T RA.

Background: Pain and fatigue are among the most debilitating symptoms of systemic sclerosis (SSc), severely impairing quality of life (QoL). Pharmacological management is often inadequate, and evidence on exercise is limited. This study aimed to evaluate the effects of a tailored exercise programme on pain and fatigue in people with SSc (PwSSc).

Methods: This European multicentre randomised controlled trial (n=6) recruited 170 PwSSc (89% limited cutaneous SSc), randomised to an exercise intervention group (EIG) or usual care group (UCG). The EIG completed a 12-week, twice-weekly supervised programme combining 30 min of high-intensity interval training (HIIT) and 15 min of resistance training (RT), in addition to usual care. The UCG received usual care alone. Outcomes were assessed at baseline, 12 weeks (primary endpoint) and 24 weeks, with pain and fatigue as primary outcomes, and QoL, depression, functional ability, musculoskeletal strength/endurance and cardiorespiratory fitness as secondary outcomes.

Results: At 12 weeks, the mean group differences for the primary, fatigue (-10.4 (95% CI 19.4 to -1.4), p<0.05) and pain (0.48 (95% CI 0.21 to 0.76), p<0.05), secondary, depression (p<0.001), QoL and self-reported function (p<0.05) and exploratory outcomes musculoskeletal strength and endurance (p<0.01), and cardiorespiratory fitness (p<0.001) were significantly improved in EIG compared with UCG.

Conclusions: A 12-week supervised combined upper body exercise programme can improve pain, fatigue, depression, QoL, function, strength and cardiorespiratory fitness in PwSSc. HIIT combined with RT is safe for the study population and may serve as an effective non-pharmacological adjunct to pharmacotherapy to manage SSc symptoms and enhance QoL.

Trial registration number: NCT05234671.

Objectives: (1) To assess the risk of haematological malignancies in individuals with systemic sclerosis (SSc) compared with individuals without SSc; (2) to explore how the risk varies across groups stratified by sex and age; and (3) to determine when these malignancies present in relation to SSc diagnosis in a population-based setting.

Methods: We performed a nationwide cohort study using high-quality administrative healthcare registers covering virtually all Swedish residents. All individuals with SSc diagnosed during 2004-2019 and matched general population comparators were included. We identified all haematological malignancies in the study population using the Swedish Cancer Register and estimated the incidence rates using Poisson regression and the HRs using flexible parametric models. We stratified by sex and age and explored the incidence over time since SSc diagnosis.

Results: We observed 1720 individuals with incident SSc and 16 983 comparators for 11 480 and 131 021 person-years, respectively. Individuals with SSc had a higher risk of haematological malignancies compared with individuals without SSc (HR 2.2, 95% CI 1.4 to 3.1), especially B-cell malignancies (HR 3.0, 95% CI 1.7 to 4.8). The incidence rate and the HR were highest in men. The SSc over-representation of haematological malignancies was most evident in individuals aged 18-49 years at SSc diagnosis. Myeloid malignancies presented around SSc diagnosis (median 0.1 (IQR 8.2) years after SSc diagnosis) while lymphoid malignancies presented a few years later (median 3.1 (IQR 9.5)).

Conclusion: Individuals with SSc are afflicted by an increased risk of haematological malignancies, especially B-cell malignancies. The risk is highest in men. Myeloid malignancies tend to present closer to SSc diagnosis than lymphoid malignancies.

Aim: To evaluate the reliability and diagnostic performance of artificial intelligence (AI) driven robotic ultrasonography (RUS) compared with human ultrasonography (HUS) performed by a trained rheumatologist for assessing synovitis in the hands of healthy controls and patients with rheumatoid arthritis (RA).

Methods: 20 healthy controls and 29 patients with RA eligible for initiation or intensification of disease-modifying anti-rheumatic drugs, with at least one clinically swollen joint in the hands, were included. The ultrasound robot scanned controls and patients twice without interval, whereas HUS was performed once. Synovitis was scored from 0 to 3 for Greyscale (GS) and Doppler (CD) by RUS (using AI software) and HUS according to the European League Against Rheumatism-OMERACT scoring system (range 0-66).Intrarobot and human-robot reliability and agreement were assessed. Furthermore, the diagnostic performance of RUS for detecting arthritis was evaluated using the clinical arthritis diagnosis as reference.

Results: Intrarobot reliability was moderate to good, with intraclass correlation coefficients (ICCs) values of 0.65 (GS) and 0.86 (CD) in patients with RA. Human-robot agreement was moderate, with ICCs of 0.59 (GS) and 0.64 (CD). At joint level, RUS obtained higher scores for MCP joints than HUS, while scores were comparable for other joint groups. The diagnostic accuracy of RUS for detecting clinically-detected arthritis was 59%.

Conclusion: A moderate to good overall agreement was seen between RUS and HUS in assessing synovitis in RA hands. However, at the joint level, low agreement was observed, particularly for MCP joints in both intrarobot and human-robot comparisons, which affected diagnostic performance.

Objectives: To evaluate the diagnostic utility of optical coherence tomography angiography (OCTA)-derived biomarkers in patients with giant cell arteritis (GCA) and to advance the pathophysiological understanding of disease-related microvascular alterations and their association with vascular manifestation.

Methods: Newly diagnosed, untreated GCA patients and healthy controls were assessed using OCTA of the optic nerve head (ONH). Skeletonised and binarised vessel densities were quantified in retinal vascular plexus and in the choriocapillaris in concentric rings around the ONH (0.5/1.0 mm diameter). Associations with clinical data, vascular ultrasound including Outcome Measures in Rheumatology Giant Cell Arteritis Ultrasonography Score (OGUS) and large-vessel involvement were evaluated using correlation and multivariable regression analyses.

Results: A total of 60 GCA patients and 69 healthy controls were prospectively enrolled. Reduced vessel density in the outer ring (1 mm) of the superficial retinal plexus was the strongest OCTA-derived discriminator of GCA (r=0.28, p=0.001), independent of visual symptoms. Multivariable regression identified lower superficial plexus density as significantly associated with GCA (β=-0.22, p=0.015). Calculated OGUS was positively associated with OCTA alterations (ρ=0.28, p=0.03), while aortic involvement was inversely associated (ρ=-0.32, p=0.02). Age was the only independent predictor of visual symptoms (β=0.173, p=0.013).

Conclusions: Our study reveals microvascular alterations in GCA, even in the absence of visual symptoms. Vessel density reduction in the superficial peripapillary plexus may serve as an early biomarker of retinal hypoperfusion. The inverse association with aortic involvement supports the concept of distinct immunophenotypes in GCA.

Objectives: To explore characteristics and treatment of patients with rheumatoid arthritis (RA) with invasive fungal infections (IFIs) and to describe infection details and outcome.

Methods: IFIs reported to the German RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) register between May 2001 and December 2023 were analysed using a two-stage approach. First, a detailed case description, including a comparison of cases by infection outcome, was conducted using routine register data and hospital discharge letters. Second, a multivariable time-dependent Cox regression model was fitted to analyse associations with IFI development using routine register data only.

Results: Among 22 535 patients with RA, 69 IFIs occurred (incidence rate: 0.65/1000 patient-years), with a case fatality of 35% (n=24). Causative pathogens were Pneumocystis jirovecii (35%), Candida spp (33%) and Aspergillus spp (13%).Patients with IFIs were on average 65.4 years old; 54% were female, 80% ever-smokers, 84% glucocorticoid (GC) users and 91% had any infection-risk associated comorbidity at hospitalisation. IFI development was associated with older age (HR 1.36 per 10 years (95% CI 1.05 to 1.76)), male sex (HR 1.92 (95% CI 1.14 to 3.21)), ever-smoking (HR 2.43 (95% CI 1.35 to 4.37)), cardiovascular disease (HR 3.03 (95% CI 1.80 to 5.10)), chronic lung disease (HR 2.09 (95% CI 1.21 to 3.61)), other autoimmune disease (HR 2.11 (95% CI 1.10 to 4.07)), and the use of GCs (HR 1.17 (95% CI 1.11 to 1.22)).

Conclusion: In patients with RA, IFIs are rare but life-threatening. They occur particularly in patients who are predisposed to infection due to relevant comorbidities, a history of smoking or both. Except for GC use, the overall impact of targeted RA treatment on the risk of IFI appears to be less relevant than that of multimorbidity.

Objective: To assess the long-term safety and efficacy of upadacitinib over 5 years in Japanese patients with moderate-to-severe active rheumatoid arthritis and an inadequate response to stable doses of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs-IR).

Methods: Japanese patients received upadacitinib 7.5, 15 or 30 mg once per day or placebo for 12 weeks in a double-blind, randomised manner. Patients who completed the placebo-controlled phase entered a long-term extension phase during which they continued the same upadacitinib dose or were switched from placebo to upadacitinib 7.5, 15 or 30 mg once per day. Blinding was maintained until dose switching from upadacitinib 30 mg to 15 mg, prior to the regulatory approval of 15 mg; the earliest switch occurred at week 132. Safety and efficacy were evaluated through week 260.

Results: In total, 121/187 (64.7%) patients who entered the long-term extension phase completed the study. The types and frequency of adverse events were comparable with those reported at week 84 and in other studies of upadacitinib. The incidences of any adverse events, serious adverse events, infection and serious infection were numerically higher on upadacitinib 15 and 30 mg than on 7.5 mg. Clinical outcomes were improved and maintained over 260 weeks; Clinical Disease Activity Index clinical remission rates after 5 years were 40.8%, 26.5% and 28.0% on upadacitinib 7.5, 15 and 30 mg, respectively (non-responder imputation).

Conclusions: Upadacitinib showed sustained efficacy with no new safety signals identified through 5 years of treatment and is a long-term treatment option for Japanese patients with rheumatoid arthritis and csDMARDs-IR.

Objective: To determine the prevalence of poor health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) in Lupus Low Disease Activity State (LLDAS) or Definitions of Remission in SLE (DORIS) remission and sustained LLDAS or sustained DORIS remission, after a 52-week therapeutic intervention.

Methods: We analysed data from four phase III trials of belimumab in SLE (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; n=2406). Sustained LLDAS/remission was defined as persistent LLDAS/remission for at least two visits, maintained through week 52. Poor HRQoL was defined as Short Form-36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores ≤the normative fifth percentile, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scores <30 and responses of 'some/moderate problems' or 'extreme/major problems' in any of the five dimensions of the three-level version of EuroQol 5-Dimension (EQ-5D) health questionnaire.

Results: At week 52, among patients in LLDAS, remission, sustained LLDAS and sustained remission, 15.7%, 13.6%, 14.3% and 9.0% reported poor SF-36 PCS, and 12.5%, 11.4%, 12.9% and 14.0% reported poor SF-36 MCS scores, respectively. The highest frequencies were reported in the physical functioning domain (24.0%-26.3%), while 18.5%-26.2% reported FACIT-F scores 30. Among EQ-5D dimensions, pain/discomfort yielded the greatest frequencies of poor HRQoL experience (27.9%-28.7%). While significant improvements were observed among patients achieving the treatment goals in all HRQoL outcomes over the 52-week study period, PCS scores remained below population norms.

Conclusions: Despite LLDAS or DORIS remission, notable proportions of SLE patients report poor HRQoL, indicating that current therapeutic goal definitions do not fully capture patients' perspectives of health.