Annals of the Rheumatic Diseases最新文献

Objectives: To analyse the similarity in clinical manifestations and laboratory findings between systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD).

Methods: Three systematic reviews (SR) were performed. One included cohort studies comparing sJIA versus AOSD that described clinical and biological manifestations with at least 20 patients in each group (SR1). The second identified studies of biomarkers in both diseases and their diagnostic performance (SR2). The last focused on diagnostic biomarkers for macrophage activation syndrome (MAS, SR3). Medline (PubMed), Embase and Cochrane Library were systematically searched. The risk of bias was assessed with an adapted form of the Hoy scale for prevalence studies in SR1 and the Quality Assessment of Diagnostic Accuracy Studies-2 in SR2 and SR3. We performed meta-analyses of proportions for the qualitative descriptors.

Results: Eight studies were included in SR1 (n=1010 participants), 33 in SR2 and 10 in SR3. The pooled prevalence of clinical manifestations did not differ between sJIA and AOSD, except for myalgia, sore throat and weight loss, which were more frequent in AOSD than sJIA because they are likely ascertained incompletely in sJIA, especially in young children. Except for AA amyloidosis, more frequent in sJIA than AOSD, the prevalence of complications did not differ, nor did the prevalence of biological findings. Ferritin, S100 proteins and interleukin-18 (IL-18) were the most frequently used diagnostic biomarkers, with similar diagnostic performance. For MAS diagnosis, novel biomarkers such as IL-18, C-X-C motif ligand 9, adenosine deaminase 2 activity and activated T cells seemed promising.

Conclusion: Our results argue for a continuum between sJIA and AOSD.

Prospero registration number: CRD42022374240 and CRD42024534021.

Objectives: To explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE).

Methods: The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group).

Results: From 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; P_{non-inferiority}=0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI -0.5% to 13.5%; P_{non-inferiority}=0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups.

Conclusions: GC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal.

Trial registration number: NCT02842814.

Objectives: Belimumab is a putative disease-modifying agent in systemic lupus erythematosus (SLE), yet the molecular underpinnings of its effects and the ability to predict early clinical response remain unexplored. To address these, we undertook a longitudinal, in-depth blood transcriptome study.

Methods: RNA-sequencing was performed in the blood of active SLE patients at baseline and following 6 months of belimumab treatment (n=45 paired samples). Clinical response was determined according to the SLE Responder Index (SRI)-4 and Lupus Low Disease Activity State (LLDAS). Weighted correlation network analysis (WGCNA) was used to uncover gene module trait associations. Reversibility of SLE susceptibility and severity gene signatures was assessed. Machine learning was used to build models predictive of response.

Results: Belimumab induced widespread transcriptome changes with downregulation of pathways related to B cells, type I/II interferon, IL-6/STAT3 and neutrophil activation. These effects were more pronounced among patients with LLDAS+ compared with to SRI-4+/LLDAS- response, with amelioration of the SLE 'susceptibility' signature observed in the former group. Unsupervised analysis unveiled gene modules enriched in neutrophil degranulation, type I interferon signalling and cytokine production to correlate positively with response at 6 months. Using neural networks, a set of 50 genes (including CCL4L2, CARD10, MMP15 and KLRC2) predicted response to belimumab with a cross-validated 84% specificity (test set). Lack of response was linked to perturbations of the cell cycle checkpoints, PI3K/Akt/mammalian target of rapamycin and TGF-beta signalling pathways.

Conclusion: Belimumab treatment ameliorates multiple innate and adaptive immunity dysregulations of SLE and may reverse the disease signature, consistent with the drug effects on reducing activity and preventing flares. Fingerprints of innate immunity correlate with robust improvement whereas DNA damage response with less responsive disease to BAFF inhibition.

Objectives: A EULAR task force was convened to develop points to consider (PtC) for patient education in physical activity and self-management of pain in young people with juvenile-onset rheumatic and musculoskeletal diseases during transitional care.

Methods: A task force of 26 people from 10 European countries followed the EULAR Standardised Operating Procedures to establish overarching principles (OAPs) and PtC based on a literature review and expert consensus. Level of evidence (LoE), grade of recommendation (GoR) and level of agreement (LoA) were determined.

Results: Two OAPs and seven PtC were formulated. The OAPs highlight the importance of personalised transitional care in rheumatology, ideally based on shared decision-making and incorporate interactive education to empower young individuals in managing their physical activity and pain. The PtC emphasise the clinical importance of patient education in these areas to improve readiness to transfer from paediatric to adult care. For two PtC, the GoR was moderate (grade B), based on individual cohort study (LoE 2b). For the remaining five PtC, the GoR was weak (grade D), based on expert opinion (LoE 5). The LoA among the task force was high, ranging from 9.4 to 9.8, except for one PtC that was 8.7.

Conclusion: These EULAR PtC establish guidance on best practices for delivering patient education in physical activity and self-management of pain during transitional care in rheumatology. The adoption of these PtC in clinical settings is recommended to standardise and optimise transitional care across European healthcare systems. Additionally, the task force expects that these PtC will drive future research and potentially shape policies across Europe.

Objectives: This work aimed to resolve the conflicting reports on Prevotellaceae abundance in the development of rheumatoid arthritis (RA) and to observe structural, functional and temporal changes in the gut microbiome in RA progressors versus non-progressors.

Methods: Individuals at risk of RA were defined by the presence of anticyclic citrullinated protein (anti-CCP) antibodies and new musculoskeletal symptoms without clinical synovitis. Baseline sampling included 124 participants (30 progressed to RA), with longitudinal sampling of 19 participants (5 progressed to RA) over 15 months at five timepoints. Gut microbiome taxonomic alterations were investigated using 16S rRNA amplicon sequencing and confirmed with shotgun metagenomic DNA sequencing on 49 samples.

Results: At baseline, CCP+ at risk progressors showed significant differences in Prevotellaceae abundance compared with non-progressors, contingent on intrinsic RA risk factors and time to progression. Longitudinal sampling revealed gut microbiome instability in progressors 10 months before RA onset, a phenomenon absent in non-progressors. This may indicate a late microbial shift before RA onset, with Prevotellaceae contributing but not dominating these changes. Structural changes in the gut microbiome during arthritis development were associated with increased amino acid metabolism.

Conclusion: These data suggest conflicting reports on Prevotellaceae overabundance are likely due to sampling within a heterogeneous population along a dynamic disease spectrum, with certain Prevotellaceae strains/clades possibly contributing to the establishment and/or progression of RA. Gut microbiome changes in RA may appear at the transition to clinical arthritis as a late manifestation, and it remains unclear whether they represent a primary or secondary phenomenon.