Clinical and experimental rheumatology最新文献

Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY).

Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints).

Conclusions: The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.

Objectives: People with systemic sclerosis (SSc) may find it challenging to obtain high-quality nutrition and diet information. Objectives were to evaluate (i) how commonly different information resources are used and (ii) perceived trustworthiness, accessibility, comprehensibility, and individualisation of resources.

Methods: We administered the Scleroderma Patient-centred Intervention Network Nutrition Information Resources Survey to participants in an international cohort. Participants were asked if they had used 26 informational resources in four categories, including (i) health care providers, (ii) websites or social media, (iii) print materials, and (iv) events, and to rate each resource on trustworthiness, accessibility, comprehensibility, and individualisation (0 = not at all to 10 = completely).

Results: 727 participants completed the survey. Most (94%) had sought nutrition or diet information from at least one resource. The most-used category was health care providers (86%), followed by print materials (68%), websites or social media (66%), and events (43%). People who had used a resource generally rated it more favourably across all domains than those who had not. The highest-rated resources across domains were conventional health care providers (doctors, registered dieticians, nurses), SSc patient organisations, SSc support groups, and university or research institution websites.

Conclusions: Respondents used many different diet and nutrition information resources. They preferred resources from conventional health care providers, affiliated with credible institutions (e.g., SSc patient organisations), or with personal connections (e.g., SSc support groups). Future research should address the limited evidence base on nutrition in SSc and assess the quality of information provided by different information resources.

Objectives: Bosentan is a dual endothelin receptor antagonist approved for the treatment of SSc digital ulcers (DU) and pulmonary arterial hypertension (PAH). Systolic pulmonary arterial pressure (sPAP) is a relevant parameter for the follow-up and prognosis of SSc-PAH. The therapeutic magnitude of bosentan in SSc-PAH is not fully understood, thus we aim to establish the degree of sPAP reduction in bosentan treated SSc-PAH patients.

Methods: We performed a systematic literature review in three databases from January 2000 to June 2023, involving sPAP measurement at transthoracic echocardiography of SSc patients before and after starting bosentan. Following the study quality assessment and data extraction, we performed random-effects meta-analysis and Egger's test for publication bias. Stratified analysis was performed for mono-/combination therapy, follow up duration (≤1 year), indication for bosentan therapy (PAH or DU/mixed).

Results: In the 11 selected manuscripts, sPAP mean difference before and after bosentan therapy was - 5.63mmHg (CI95% -9.79 to -1.48, p=0.0078). In stratified analysis, sPAP mean was significantly different before and after bosentan therapy only for studies considering < 1 year of follow-up (p=0.0020), monotherapy (p=0.0140) and the strict indication for PAH (p=0.0002).

Conclusions: Bosentan significantly decreases sPAP, a relevant prognostic marker, especially in overt SSc-PAH. However, bosentan did not decrease sPAP when started for DU/mixed indication nor for follow-up>1 year. The burden of publication bias was significant. Therefore, further studies are required to assess bosentan's haemodynamic effect in high-risk patients for SSc-PAH.

Objectives: Conflicting results about clinical and subclinical atherosclerosis in systemic sclerosis (SSc) and the associated risk factors have been reported. Hence, we aimed to determine the prevalence of clinical and subclinical atherosclerosis in a large number of Italian SSc patients and the associated risk factors.

Methods: This study included 613 SSc patients from 11 Italian tertiary Rheumatologic Units. All patients underwent full history taking, clinical examination, and relevant laboratory and radiological investigations. Doppler ultrasonography (US) of the common carotid and upper and lower limbs was performed to measure carotid and femoral intima-media thickness (cIMT and fIMT), and carotid and peripheral atheroma plaques. Doppler US of the brachial artery was performed to measure flow-mediated dilatation (FMD).

Results: Patients were mostly women (91.4%) with a median age of 61 years (range, 20-100); a median disease duration of 14 years (range, 0-77) from the onset of the first non-Raynaud's phenomenon (RP); 9.3% had a history of clinical atherosclerosis (9 stable/unstable angina, 21 myocardial infarctions, 24 heart failure, 3 strokes, 8 transient ischaemic attack, 6 intermittent claudication, 10 atrial thrombo-embolism). In 37.1% of patients, subclinical atherosclerosis was detected, after excluding those with a history of clinical atherosclerosis. The prevalence of clinical and subclinical atherosclerosis was higher than that reported by the European Society of Cardiology and observational studies that enrolled Italian healthy individuals as a control group, respectively.

Conclusions: A higher prevalence of clinical and subclinical atherosclerosis was detected in SSc Italian patients and correlated with traditional and SSc-related risk factors.

Objectives: The aim of this study was to investigate the predictive value of uric acid (UA) in prognosis of pulmonary artery involvement (PAI) in patients with Takayasu's arteritis (TAK).

Methods: A total of 166 TAK patients were enrolled in the study, including 76 with PAI and 90 without. Outcomes of 144 TAK patients were followed up and recorded. The possible associations between serum UA levels and incidence of PAI in TAK and PAI-related prognosis of TAK patients were examined using different statistical models.

Results: The serum UA levels were significantly higher in TAK patient with PAI than TAK patients without PAI. Multivariate logistic regression analysis indicated that serum UA level ≥284.5 umol/L was associated with an increasing incidence of PAI in TAK (OR: 2.108, 95% CI: 1.063 to 4.180; p=0.033). Kaplan-Meier survival analysis showed that TAK patients with serum UA level ≥328.1 umol/L had a significantly higher cumulative incidence of PAI-related adverse events compared to TAK patients with serum UA level <328.1 umol/L (p=0.008). Multivariate Cox proportional hazard regression analysis revealed that serum UA level ≥328.1 umol/L (HR: 2.595, 95% CI: 1.198 to 5.622; p=0.016) was a PAI-related prognostic risk factor for TAK.

Conclusions: Elevation of serum UA level was associated with an increasing risk of PAI and PAI-related adverse event in patients with TAK, indicating its potential as a predictor for identification of PAI onset and worsening in TAK patients.

Objectives: Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis.

Methods: Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured.

Results: Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP.

Conclusions: IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Objectives: Patients with fibromyalgia syndrome (FM) often suffer from sleep disorders, adversely affecting their prognosis. Active non-pharmacological therapies are considered the mainstay of treatment for FM, but the optimal treatment choice remains contentious. We aimed to compare and rank community-based non-pharmacological interventions for FM with sleep disorder by quantifying information from randomised controlled trials (RCTs).

Methods: Two authors independently selected studies and extracted data. We searched Embase, MEDLINE, PubMed, CNKI, Scopus, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) from the database inception to June 2022. Network meta-analyses were conducted using a frequency-based method. The study protocol is registered with the Prospective Register of Systematic Reviews (PROSPERO, CRD 42022373704). Eleven RCTs (n=729) were included in the analysis.

Results: Mindfulness-based therapy (MBT) (SMD=-0.84 (95% CI: -1.49 to -0.20)) and cognitive behavioural therapy (CBT) (SMD=-0.54 (95% CI: -1.04 to -0.04)) were associated with significantly improved sleep symptoms in a patient with FM compared with usual care.

Conclusions: MBT exhibited the highest probability (91.14%) of being the most effective intervention in sleep improvement, followed by CBT (72.39%). MBT exhibited marked advantages over other interventions and is likely to have optimal efficacy in ameliorating sleep disorders.