Scandinavian Journal of Rheumatology最新文献

Objectives: The objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population.

Method: Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18-85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis. Patients administered three consecutive self-injections at home. Descriptive statistics regarding baseline characteristics, retention rates, and reasons for withdrawal were assessed, along with the Beliefs about Medicines Questionnaire.

Results: In total, 59 patients participated (Netherlands 25, Denmark 15, Sweden 19). Most subjects (71%) were women, with a mean ± sd age of 55 ± 16.2 years and mean disease duration 12 ± 8.8 years. Six patients (10%) started CZP de novo and the remaining patients switched device. The overall retention rate was 42% after 52 weeks, declining to 38% after 104 weeks. A sharp decline, 34%, was seen at week 8. Between weeks 32 and 112, only four patients (6.8%) withdrew from the study. The primary reason for withdrawal was the patient's request. Stratification by country showed significant differences for some outcomes.

Conclusion: An initial large dropout was evident within the first 8 weeks, with almost no dropouts thereafter. The reasons for withdrawal were primarily patient requests. Thus, the injection experience must be tailored carefully when selecting patients for new autoinjector e-Devices to enhance retention rates and patient satisfaction.

Objective: To investigate changes in socioeconomic inequalities in patient-related outcomes and pain medication use, following participation in a digital self-management intervention for osteoarthritis (OA) in Sweden.

Method: Participants with hip/knee OA enrolled in the digital intervention were included. Self-reported outcomes collected were the numerical rating scale (NRS) pain, activity impairment, general health, Knee/Hip injury and Osteoarthritis Outcome Score (KOOS-12, HOOS-12) Pain, Function, and Quality of Life subscales, 5-level EuroQol 5 Dimensions (EQ-5D-5L), Patient Acceptable Symptom State (PASS) for function, walking difficulties, fear of movement, wish for surgery, pain medication use, physical function measured by the 30s chair-stand test, and level of physical activity. Educational attainment was used as a socioeconomic measure and the concentration index was used to assess the magnitude of inequalities at baseline and 3 month follow-up.

Results: The study included 21,688 participants (mean ± sd age 64.1 ± 9.1 years, 74.4% females). All outcomes except for PASS demonstrated inequalities in favour of highly educated participants at both time-points, with highly educated participants reporting better outcomes. At 3 month follow-up, the magnitude of inequality widened for activity impairment, but narrowed for NRS pain, EQ-5D-5L, KOOS-12/HOOS-12 Pain and Function, physical function, and wish for surgery. There were no statistically conclusive changes in the magnitude of inequalities for the remaining outcomes.

Conclusions: There were inequalities in patient-related outcomes in favour of those with higher education among participants of a digital self-management intervention for OA, although the magnitude of these pre-existing inequalities generally narrowed after the 3 month intervention.

Objective: Patients with primary Sjögren's syndrome (pSS) have an increased risk of lymphoma, especially mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands. Risk factors for lymphoma are well known, but there are no studies on screening by imaging. Therefore, we aimed to assess the usefulness and adverse effects of ultrasound of the major salivary glands and neck as lymphoma screening.

Method: A retrospective, single-centre, analysis of imaging studies in pSS patients was conducted. Imaging studies were classified as either screening examinations (asymptomatic patients) or occasion-related (imaging due to signs of lymphoma or at least moderate systemic activity). Results were categorized as: not suspicious; requiring control; triggering tissue sampling with exclusion of lymphoma; or triggering tissue sampling with diagnosis of lymphoma.

Results: The study included 134 patients and covered 1031 patient-years. Lymphoma was diagnosed in 15 patients (11.2%), all of whom had clinical signs of lymphoma at the time of diagnosis. During this period, 569 screening examinations and 179 occasion-related examinations were conducted. None of the screening examinations detected lymphoma, but follow-up imaging was recommended in 17.1% (95% CI 14.2-20.4%) and invasive exclusion of lymphoma was performed in 0.5% (95% CI 0.1-1.5%). In contrast, lymphoma was detected in 6.1% (95% CI 3.5-10.6%) of occasion-related examinations.

Conclusion: pSS patients with neither signs of lymphoma nor increased systemic disease activity did not benefit from screening. In contrast, patients with symptoms of lymphoma or at least moderate systemic activity can benefit from imaging of the neck and major salivary glands.

Objective: The family of protein disulphide isomerases (PDIs) is a group of oxidoreductases that catalyze the oxidation, reduction and isomerization of disulphide bonds. Recent studies have shown that overexpression of one of the family enzymes, ERp46, potentiates arthritis severity, suggesting that the PDI family participates in arthritis pathogenesis. This study investigated the role of another PDI member, ERp72, in autoantibody-induced arthritis.

Methods: Using the Cre-LoxP method, a mouse strain lacking ERp72 (ERp72^-/- mice) was generated. Autoantibody-induced arthritis was induced in both ERp72^-/- and ERp72^+/+ control mice by injecting serum from K/BxN mice. The synovial inflammation severity was evaluated by joint diameter measurements and histological analysis. Proinflammatory cytokines expression in joint tissue and plasma was assessed by quantitative real-time PCR and ELISA.

Results: : The absence of ERp72 in the joints, white blood cells, spleen, thymus, and bone marrow of ERp72^-/- mice was confirmed. In the K/BxN serum transfer-induced arthritis (STIA) model, ERp72^-/- mice exhibited exacerbated arthritis compared to ERp72^+/+ mice, with greater joint swelling, bone and cartilage erosion, and synovial inflammation. Furthermore, ERp72^-/- mice exhibited increased expression of IL-1β, IL-6 and TNF-α in inflamed joint tissues and higher IL-6 levels in plasma. Conversely, IL-10 levels were lower in ERp72^-/- mice inflamed joints than in ERp72^+/+ mice. Notably, the basal TNF-α level in the blood of ERp72^-/- mice was significantly higher than in ERp72^+/+ mice.

Conclusion: ERp72 plays a key role in the negative regulation of autoantibody-induced arthritis.

Objectives: In axial spondyloarthritis (axSpA), patient-perceived quality of life/global functioning and health (GH) can be assessed using disease-specific [Assessment of SpondyloArthrit is international Society Health Index (ASAS-HI)] or generic [(3-level EuroQol 5 Dimensions (EQ-5D-3L)] scores. Our objectives were to explore the link between these scores and to define thresholds for good and poor GH.

Method: We conducted a post-hoc analysis of the cross-sectional ASAS-PerSpA study for patients fulfilling ASAS criteria for axSpA. The ASAS-HI and EQ-5D scores were analysed visually (distribution, scatterplot) and through Spearman correlation and agreement (deciles). To determine cut-offs for good and poor GH on EQ-5D based on the validated ≤5 and ≥12 cut-offs for ASAS-HI, respectively, receiver operating characteristics (ROC) curves and distribution-based methods were applied. Validity was assessed using crude concordance and prevalence-adjusted bias-adjusted kappa; discordance between groups was explored.

Results: In 2651 patients (median age 41.0 years, 66.5% men), the correlation between ASAS-HI and EQ-5D was high (r = -0.73) and agreement (between deciles) was moderate (weighted kappa = 0.51). Both ROC areas under the curve were 0.86; thresholds of 0.69 and 0.54 for EQ-5D were chosen for good and poor GH, respectively. Crude concordances and agreement were satisfactory (0.80-0.81 and 0.60-0.61, respectively). The EQ-5D cut-off for good GH performed better than that for poor GH.

Conclusion: ASAS-HI and EQ-5D were highly correlated but did not fully overlap. We propose EQ-5D thresholds corresponding to the ASAS-HI thresholds for good and poor GH; however, caution is needed when assessing poor GH with EQ-5D. These findings will be useful to compare GH when only one of the outcome measures is available.

Objective: The north-south gradient hypothesis proposes that individuals with rheumatoid arthritis (RA) residing in southern regions manifest a younger age of onset and milder disease compared to their northern counterparts. This study aimed to compare treatment-naïve, new-onset RA patients in Denmark and Turkey, examining demographic, clinical, laboratory, and genetic parameters.

Method: Prospective data collection was conducted, with all patients meeting the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Shared epitope (SE) allele carrier frequencies were examined for genetic comparisons between patients and normal controls.

Results: Out of 223 RA patients, 109 were Danish and 114 Turkish. Danish patients exhibited a median age at onset of 60 years, whereas Turkish patients were younger at 51 years (p = 0.0007). The Danish cohort displayed significantly more swollen and tender joints, resulting in higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP). Danish RA patients and controls possessed more RA risk-enhancing alleles (S2 + S3P) and fewer risk-protective (S1 + S3D) alleles than Turkish patients and controls.

Conclusion: This study substantiates the north-south gradient hypothesis, highlighting that new-onset RA patients in Denmark tend to experience an older age of onset and more severe disease activity than their Turkish counterparts. Variations in risk-enhancing alleles and fewer risk-protective alleles in Danish patients and controls are associated with these distinctions. Future research should investigate the genetic and environmental factors underlying these regional disparities, exploring their persistence in the long-term course of the disease through follow-up studies.

Objective: To investigate the function of mitophagy in instructing T-cell differentiation of patients with rheumatoid arthritis (RA).

Method: The mRNA and protein levels of optic atrophy protein-1 were detected in T cells from 94 RA patients and 37 age- and sex-matched healthy individuals by quantitative polymerase chain reaction and Western blotting. The impact of mitophagy on the differentiation of T cells was determined by flow cytometry. The therapeutic effect of targeting mitophagy was explored in humanized RA chimeras.

Results: Our study showed that T cells exerted high levels of mitophagy in RA patients. Since multiple T-cell subtypes play crucial roles in RA, we determined that mitophagy had a significant impact on the differentiation of tissue-resident memory T (Trm) cells, but not Th1 or Th17 cells. Importantly, we demonstrated that inhibiting mitophagy significantly reduced the number of Trm cells and downregulated inflammatory responses, as evidenced by diminished levels of T cell receptor β, interferon-γ, and interleukin-17A, in the humanized RA chimeras.

Conclusions: Mitophagy is elevated in RA T cells, leading to maldifferentiation of Trm cells in RA patients. Since these findings were obtained from clinical patients, mitophagy may be a potential therapeutic target for RA treatment.

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA.

Method: Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws.

Results: We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway.

Conclusions: This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.