Scandinavian Journal of Rheumatology最新文献

Objective: Lung computed tomography (CT) is a valid method for the detection and assessment of the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. The objective of this study is to conduct a comparative analysis of the characteristics of individuals with RA-ILD, with and without radiographic progression, determined using lung CT scans.

Method: In this retrospective observational study, three radiologists re-evaluated CT scans of RA-ILD patients who had at least one follow-up CT. The lungs were divided into upper, middle, and lower zones, with equal slices. Progression was defined as the involvement of more zones in the vertical extent by the same elementary findings or the emergence of more severe findings in the same zones compared to the previous examination. Logistic regression analysis was used to assess the possible factors identified in univariate analysis.

Results: This study included 104 patients with 215 lung CT scans for analysis. Radiographic progression was seen in 43 patients (41.3%). Male sex, findings compatible with ILD on the last X-ray, age at diagnosis of ILD > 50 years, and presence of ground-glass opacity on CT were more common in the group with progression. In multivariate analysis (adjusted for ILD disease duration), findings consistent with ILD on chest X-ray and male sex were independent risk factors for progression, while taking methotrexate (ever) was an independent protective factor for progression.

Conclusion: Our findings indicate a negative association between methotrexate use and ILD progression. These results should be confirmed in further studies.

Objective: Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated.

Method: Interleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression.

Results: ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E₂, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes.

Conclusion: Knockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.

Objective: To study the impact of tumour necrosis factor-α inhibitor (TNFi) therapy on the use of non-steroidal anti inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in Iceland.

Method: This registry cohort study used data from the nationwide database on biologics in Iceland (ICEBIO) and the Icelandic Prescription Medicines Register on disease activity, and filled prescriptions for NSAIDs, to study the period from 2 years before to 2 years after initiation of a first TNFi. Five randomly selected individuals from the general population matched on age, sex, and calendar time for each patient served as comparators.

Results: Data from 940 patients and 4700 comparators were included. Patients with arthritis were prescribed 6.7 times more defined daily doses of NSAIDs than comparators (149 vs 22 per year). After TNFi initiation, NSAID use decreased to a mean of 85 DDD per year, or by 42% in RA, 43% in PsA, and 48% in axSpA. At TNFi initiation, the quintile of axSpA patients who used most NSAIDs reported significantly worse pain (mean ± sd 66 ± 21 vs 60 ± 23 mm), global health (70 ± 20 vs 64 ± 23 mm), and Health Assessment Questionnaire score (1.21 ± 0.66 vs 1.02 ± 0.66) than the other patients, whereas no significant differences were observed in the groups with peripheral arthritis.

Conclusion: Patients with inflammatory arthritides requiring TNFi therapy use more NSAIDs than matched comparators, and consumption decreased following TNF initiation. Patient-reported measures are not associated with high NSAID use in patients with peripheral arthritis.

Objective: The efficacy of Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) has been clearly shown. However, information on comparative drug retention rates (DRRs) of different JAKi is heterogeneous. The aim of this study was to compute and compare DRRs of different JAKi in a large cohort of RA patients.

Method: Patients with RA treated with at least one JAKi and followed up at our centre were retrospectively identified. DRRs of each JAKi were computed at 24 months. The association of baseline features with drug persistence was tested. Variations in 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) scores between baseline and 12 months were analysed.

Results: The study included 365 patients, with a total of 463 therapy courses. Tofacitinib was the most prescribed JAKi (33%), followed by baricitinib (25%), upadacitinib (24%), and filgotinib (21%). The mean treatment duration was 24 ± 17 months, with a maximum of 70 months. At 24 months, the overall DRR was 86%. DRRs were not significantly different across different JAKi. The only baseline predictor of treatment discontinuation was previous treatment with a biological disease-modifying anti-rheumatic drug (bDMARD) (hazard ratio 1.65, 95% confidence interval 1.08-2.53; p = 0.021). There were significant reductions in DAS28-CRP and CDAI 1 year after treatment start.

Conclusions: In our large, monocentric cohort, the overall 24 month DRR for JAKi was greater than 80%. No significant differences in retention were found among different JAKi. Persistence was lower in patients who had previously been treated with other bDMARDs.

Objective: To assess the efficacy and safety of iguratimod in adult patients with active axial spondyloarthritis (axSpA).

Method: This randomized, double-blind, placebo-controlled clinical trial lasted for 28 weeks. Patients with axSpA were randomized 1:1 to receive iguratimod 25 mg twice daily or a placebo. All patients also took celecoxib 200 mg twice daily for the first 4 weeks and on demand from 4 to 28 weeks. The primary endpoints were ASAS20 at 4 weeks and the non-steroidal anti-inflammatory drug (NSAID) index at 28 weeks. Other assessment variables included ASAS40, ASAS5/6 response rates, Spondyloarthritis Research Consortium of Canada (SPARCC) scores, and adverse events.

Results: In total, 35 patients completed the study and were included for analyses. The median (interquartile range) NSAID index was 43.8 (34.9-51.8) in the iguratimod group, which is significantly lower than 68.9 (42.5-86.4) in the placebo group (p = 0.025). ASAS response rates and changes in disease activity scores were similar between the iguratimod and placebo groups. Patients in the iguratimod group had more improvement in median (interquartile range) SPARCC scores for sacroiliac joints than did those in the placebo group [71% (54-100%) vs 40% (0-52%), p = 0.006]. Iguratimod combined with celecoxib was not associated with a greater risk of adverse effects than was monotherapy with celecoxib. No severe adverse events occurred.

Conclusions: In the treatment of active axSpA, iguratimod has a potential NSAID-sparing effect, and may also reduce magnetic resonance imaging-assessed bone marrow oedema in sacroiliac joints. Iguratimod provides an additional treatment option for patients with active axSpA.Clinical trial registration numberChiCTR2000029112, Chinese Clinical Trial Registry (http://www.chictr.org.cn).

Objective: Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature.

Method: Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment.

Results: Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active.

Conclusion: vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Objective: Interstitial lung disease (ILD) is an important cause of mortality in patients with rheumatoid arthritis (RA). Early RA-ILD detection is essential to improve prognosis. Here, we investigated eight serological biomarkers that may contribute to RA-ILD detection.

Method: Fifty-five patients from the Early Rheumatoid Arthritis Program were evaluated for ILD with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) using the SCAPIS protocol. Blood samples were obtained for biomarker analysis, and patients' clinical records were reviewed. We defined ILD using five different models based on the measurements used to confirm ILD: Model A = HRCT; B = PFTs; C = A plus B; D = C plus symptoms; and E = D plus inhalations.

Results: Among 55 patients, two had an ILD diagnosis before the study, but over one-third fulfilled the ILD criteria. Cancer antigen 15-3 (CA15-3) and matrix metalloproteinase-7 (MMP-7) differentiated between RA with and without ILD (all p < 0.05). Surfactant protein D (SP-D) showed similar trends, as did macrophage inflammatory protein-1β (MIP-1β) and chitinase 3-like protein-1 (YKL-40). Based on Pearson's correlation coefficients, MIP-1β and YKL-40 were significantly correlated with DAS28 (MIP-1β: 0.3; YKL-40: 0.4), ESR (MIP-1β: 0.3; YKL-40: 0.4), and CRP (only MIP-1β: 0.4) (all p < 0.05). CA15-3 was correlated with rheumatoid factor and anti-citrullinated peptide antibodies (Pearson's correlation 0.3; both p = 0.03).

Conclusions: CA15-3 was the most significant biomarker for ILD detection in RA patients with stable low disease activity, closely followed by MMP-7. SP-D, MIP-1β, and YKL-40 may also contribute to RA-ILD diagnosis.

Objectives: Early identification of interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA) is a challenge for clinicians. The aim of this study was to evaluate screening algorithms for ILD by comparing the proportion of patients assigned a high-risk profile by three recently proposed models.

Method: We used the four-factor risk score, categorizing patients into high and low risk; the ILD screening criteria, categorizing patients into high, intermediate, and low risk; and the risk score for detection of subclinical RA-ILD, with four different risk categories, on patients with RA followed for 5 years after the RA diagnosis with pulmonary function tests, dyspnoea score, and pulmonary imaging.

Results: The four-factor risk score identified 22% of the cohort (25/115) as eligible for further ILD investigations, while the ILD screening criteria identified 37% as high risk (43/115) and 34% as intermediate risk (39/115). The risk score for detection of subclinical RA-ILD identified 44% of the cohort as being at increased risk, with 7% in the highest risk group. The agreement between high-risk groups in the two clinical ILD screening models was moderate (kappa 0.43). Three patients in the cohort had clinical or subclinical ILD, and they were identified as high risk in the two clinical models.

Conclusion: The three algorithms identified approximately one-third of the cohort as being at increased risk of ILD. Further development and validation of these algorithms are needed to reduce false positives and balance the potential benefit of earlier ILD diagnosis and healthcare resources used for respiratory assessment.