Clinical and experimental rheumatology最新文献

Objectives: Despite significant savings with biosimilars, their negative perception can lead to the occurrence of a nocebo effect (NE), therefore we aimed to quantify the NE in inflammatory rheumatism after switching from adalimumab or etanercept originators to biosimilars.

Methods: This retrospective study was conducted in 4 hospitals in Normandy, France between January 2018 and July 2022. The study included patients with rheumatoid arthritis or spondyloarthritis in remission under adalimumab or etanercept originators before switching to biosimilars. The occurrence of a NE was considered in patients who did not maintain biosimilars at 12 months and who presented a subjective adverse event (AE). A comparative analysis of the quantitative data collected before and after switching was performed. The AE that led to biosimilar discontinuation was identified. Additional analyses were performed to identify potential risk factors for the occurrence of a NE.

Results: Among 183 patients included,13.1% presented a NE. Objective AEs were observed, including rheumatism reactivation (15.3%), intolerance (8.2%), infection (1.6%) and allergic reactions (0.5%). Morning stiffness duration was significantly different before and after the switch in the spondyloarthritis group (p=0.01). No risk factors were associated with the occurrence of a NE within the limits of the studied parameters.

Conclusions: The occurrence of a NE after switching to a biosimilar remains acceptable. It appears less frequent when the switch is supervised by the practitioner rather than being systematic (up to 33% in some countries). A shared medical decision seems to be essential in a subset of patients, which remains to be defined.

Psoriatic arthritis is a very pleomorphic inflammatory disease characterised by its association with psoriasis and the development of a wide spectrum of comorbidities that can impact patients' prognosis and quality of life.In recent years, several new drugs have been developed, showing significant efficacy in alleviating symptoms and signs, while maintaining a generally favourable safety profile. Despite these advancements, the management of PsA remains potentially suboptimal. Indeed, a percentage of patients do not respond to therapies, or they may improve only in limited outcomes, resulting in a challenge for the management of the burden of disease.In this paper we reviewed the literature on PsA from January 1st 2022 to July 1st 2024.

Objectives: Th1/Th2 shift occurs during pregnancy. Systemic lupus erythematosus (SLE) flares may induce the dysregulation of Th1 and Th2 cells. We aimed to investigate the dynamic changes of Th1/Th2 associated transcription factors and cytokines in patients with SLE during pregnancy.

Methods: Twenty-five pregnant patients with SLE and twenty-two healthy age-matched women served as controls from September 2021 to March 2022 were enrolled in the study. Real-time quantitative reverse transcription polymerase chain reaction analysis of peripheral blood mononuclear cells were performed to measure the expression of Th1 specific transcription factors T-bet, cytokine IFN-γ, and Th2 specific transcription factors GATA3, cytokine IL-4. The main statistical analysis methods were t test, Mann-Whitney U-test, Pearson correlation and Spearman rank correlation analysis.

Results: The mRNA level of IFN-γ and the relative expression of T-bet/GATA3 and IFN-γ/IL-4 in SLE patients were significantly higher than those in healthy individuals, whereas the GATA3 expression is lower in pregnant patients with SLE (p<0.001, p<0.05, p<0.05 and p<0.01 during the whole pregnancy, respectively; p<0.05, p<0.01, p<0.05 and p<0.05 specifically for the 3rd trimester, respectively). There were significant correlations between T-bet and IFN-γ (r=0.492, p<0.05), and between T-bet/GATA3 and IFN-γ/IL-4 (r=0.482, p<0.05).

Conclusions: Our work indicates that in SLE patients Th1/Th2 shift is blocked with up-regulation of Th1 cell function and insufficient Th2 polarisation during pregnancy, which may be involved in adverse pregnancy outcomes.

Objectives: Systemic sclerosis (SSc), a chronic autoimmune disorder, characterised by local inflammation and progressive fibrosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) has been established as a key mediator in fibrotic processes across multiple organs, primarily through binding to its receptor, fibroblast growth factor-inducible 14 (Fn14). However, the precise role of the TWEAK/Fn14 signalling in SSc pathogenesis remains unclear. This research probes into the potential involvement of TWEAK in the pathological progression of SSc.

Methods: The skin tissue was harvested from SSc patients and a bleomycin (BLM)-induced mouse model. Immunohistochemistry staining, Western blotting and detection of hydroxyproline content were applied to determine the effect of Fn14 signalling on skin fibrosis in SSc.

Results: TWEAK and Fn14 were markedly elevated in SSc cutaneous lesions. In the SSc mouse model, exogenous TWEAK partially exacerbated cutaneous fibrosis and the infiltration of inflammatory cells. Conversely, an Fn14 antagonist significantly reduced BLM-induced histological changes in the skin tissue.

Conclusions: These findings demonstrate that the TWEAK/Fn14 signalling axis contributes to SSc progression by exacerbating local inflammation and fibrosis. Targeting the Fn14 signalling pathway holds potential for the development of novel therapeutic approaches for SSc.

Objectives: Body mapping of normal values of skin thickness and hardness may be a useful aid in daily practice. By employing non-invasive techniques, our pilot study provides these values in healthy individuals using high frequency ultrasound (HFUS) and durometry in areas used to evaluate the modified Rodnan skin score (mRSS).

Methods: One-hundred-fifty-two healthy volunteers from Ghent and Genova University Hospitals (mean ages 31.2, 35.5, and 64.9 years), were evaluated to exclude rheumatologic diseases. HFUS and durometry were used to assess the dermal status in mRSS areas. Exploratory analyses were performed to assess the impact of demographic and anthropometric characteristics on intra-subject skin measurements. Statistical analysis was performed with Datatab®.

Results: The upper and lower arms exhibited significantly higher durometry values and lower dermal thickness compared to the trunk regions, underscoring distinct variations across these areas (all p<0.05). The hardest skin was found on the finger, while the thickest dermal measurements were at the abdomen and thighs. Dermal thickness was higher in men in multiple areas in the three cohorts, albeit with relatively modest effect sizes (r coefficients ranging between 0.02 and 0.6). Despite the presence of significant inter-group differences in dermal thickness, HFUS mapping showed similar topographical distributions in both centres.

Conclusions: Our study offers a comprehensive skin mapping status in healthy individuals. Key findings indicate lower dermal thickness in the upper arms, legs, and feet, and higher skin hardness in peripheral areas like fingers, compared to truncal regions.This skin mapping pilot study might provide the normal distribution values in outpatient clinics for physicians to be used when comparing the same areas in pathological conditions like systemic sclerosis-related fibrotic skin.

Objectives: The challenge of achieving low disease activity or remission in psoriatic arthritis (PsA) is an unmet need for many patients. Persistent disease activity in PsA may require treatment adjustments due to its complex pathogenesis and varied tissue involvement, highlighting the need for dedicated definitions. This study evaluates patients' frequency and contributing factors with potential "difficult-to-treat PsA (D2TPsA)", similar to the EULAR definition of D2T rheumatoid arthritis.

Methods: A retrospective study was conducted at two tertiary centres to define potential D2TPsA, defined as failure of ≥1 conventional synthetic disease-modifying anti-rheumatic drug (DMARD) and ≥2 biological or targeted synthetic DMARDs with different mechanisms of action.

Results: Of the 171 patients included in the study, 116 (67.8%) were women; the average age was 48.16 ±11.23 years. D2TPsA was detected in 33 patients (19.3%). This group exhibited a longer disease duration, higher disease burden (median number of tender and swollen joints, patient and physician global evaluation, morning stiffness, erythrocyte sedimentation rate and C-reactive protein, DAPSA), HLA-B27 positivity, and higher prevalence of peripheral involvement. Secukinumab usage and mean glucocorticosteroid dosage were significantly higher in the D2TPsA group. Comorbidities such as fibromyalgia (FM) and diabetes mellitus (DM) and the median number of comorbidities were significantly higher in D2TPsA. In multivariate analysis, FM, DM, and HLA-B27 positivity were independently associated with D2TPsA.

Conclusions: This study underscores the impact of comorbidities on PsA disease activity and emphasises the need for further research to differentiate treatment challenges influenced by comorbidities from true treatment resistance.

Objectives: To perform a systematic review and meta-analysis to assess the clinical efficacy of collagen-based supplements on knee osteoarthritis (OA) symptoms.

Methods: Until October 2023, we conducted searches on the MEDLINE, EMBASE, Web of Science, and Scopus databases to identify randomised controlled trials (RCTs) that reported the effects of oral collagen-based supplements on knee OA. Quantitative data from outcomes were pooled using a random- or fixed-effects model (depending on inter-study variability) and the generic inverse variance method. The Cochrane Risk of Bias 2.0 tool was employed to assess the risk of bias.

Results: This systematic review incorporated information of 870 participants included from 11 RCTs, with 451 allocated to the collagen supplementation group and 419 to the placebo group. The meta-analysis revealed an overall significant improvement of both function [MD, -6.46 (95% CI -9.52, -3.40); I2=75%; p=0.00001] and pain scores [MD, -13.63 (95% CI -20.67, -6.58); I2=88%; p=0.00001], favouring collagen supplementation.

Conclusions: The results of this meta-analysis suggest that oral collagen administration relieves OA symptoms. Our findings revealed noteworthy improvements, statistically and clinically, in both functional and pain scores.

Objectives: We aimed to investigate choroidal involvement and the degree of anterior chamber inflammation in a cohort of patients with juvenile idiopathic arthritis (JIA) without clinical signs of active uveitis and to compare it with healthy controls (HC).

Methods: Enhanced-depth imaging optical coherence tomography (EDI-OCT) scans of 21 patients diagnosed with JIA and 22 HC of equal age were acquired. Images were binarised to measure subfoveal choroidal thickness (SCT), nasal choroidal thickness (NCT), temporal choroidal thickness (TCT), total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascular index (CVI). Patients also underwent a measurement of the degree of inflammation in the anterior chamber by laser flare meter (LFM).

Results: No significant differences were found in the choroidal thickness in the subfoveal region (p=0.274), nasally to the fovea (p=0.568) and temporally to the fovea (p=0.430) between JIA patients and HC. No statistically significant difference in the choroidal area (TCA, LA and SA) between the JIA patients and HC were found. Moreover, CVI was not significantly different between the two groups (p=0.166), while the LFM of the JIA patients and HC (p=0.002) revealed a statistically significant difference.

Conclusions: In the absence of active uveitis, choroidal thickness and vascularity are not significantly different in JIA patients and HC.

Objectives: To assess the association between life events and subsequent diagnosis of systemic autoimmune rheumatic diseases (SARDs) by comparing siblings discordant for SARDs and unrelated controls.

Methods: Life events 12 months prior to SARD diagnosis/reference date were queried using the Interview for Recent Life Events in 227 adults (96 probands with SARDs, 78 siblings, 53 controls). Probands were matched by age, sex, and race with their unaffected siblings or with unrelated controls. Logistic regression was used to calculate the relative odds of SARDs in relation to life events scores, adjusting for age, sex, race/ethnicity, education, and ever smoking.

Results: The study identified consistent trends of probands reporting greater numbers of total and highly stressful events, and higher stress ratings than their unaffected siblings. Probands reported greater numbers and higher stress ratings of total, uncontrollable, and undesirable events compared to unrelated controls (p<0.001-0.024). The number of highly stressful events and the scores of weighted major events were also greater in probands and siblings compared to unrelated controls (p<0.001-0.046). The number of total, major, uncontrollable, undesirable, and highly stressful life events (OR range 1.31-1.64, p-value range 0.001-0.049), along with their corresponding stress ratings (OR range 1.22-1.51, p-value range <0.001-0.016), were associated with higher odds of SARD diagnosis, based on probands compared to controls.

Conclusions: This case-control study of life events preceding SARDs diagnosis using a validated life events questionnaire provides support for an aetiologic role of negative life events and psychological stress in SARDs among adults.