Scandinavian Journal of Rheumatology最新文献

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.

Objective: Currently, expedited by the coronavirus disease 2019 pandemic, there is high demand for allocating patients in a state of low disease activity to telehealth, ideally based on remote measurements. This cross-sectional study assesses the discriminative accuracy of the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire regarding high and low disease activity. Furthermore, we aimed to optimize this classification, developing a remote triage score based on RAID and other patient-reported outcome measures (PROMs).

Method: Data were acquired from an outpatient clinic cohort of chronic rheumatoid arthritis patients at a large trainee hospital in the Netherlands. Patients were divided into high and low disease categories, based on 28-joint Disease Activity Score-C-reactive protein. Least absolute shrinkage and selection operator logistic regression were performed, including RAID item scores and other PROMs. Receiver operating characteristics curves and areas under the curve (AUCs) were obtained, and cut-off scores were based on predefined criteria of 90% and 95% sensitivity.

Results: In total, 278 patients were analysed, of whom 77.2% were identified as having low disease activity. RAID results correlated with DAS28-CRP, showing good performance. The regression model included the RAID items pain and functional disability assessment, and the self-reported swollen joint count (SR-SJC). With an AUC of 0.88 (95% confidence interval 0.84-0.92), this model performed better than the RAID total score.

Conclusion: A remote triage score based on a composite score of pain, functional disability assessment, and SR-SJC can detect a sufficient proportion of patients with low disease activity who can be allocated to remote consultations.

Objective: To assess the agreement between child- and parent-reported orofacial symptoms in the Danish version of the patient questionnaire Assessment of Orofacial Symptoms in Juvenile Idiopathic Arthritis.

Method: This cross-sectional study was conducted at Aarhus University in March 2023. Eligible candidates were consecutive subjects with juvenile idiopathic arthritis (JIA) and temporomandibular joint involvement accompanied by a parental proxy for examination in the Craniofacial Clinic. After obtaining written informed consent, the questionnaire was completed individually and separately by the child and the parent without any communication between them. The level of agreement was analysed using Cohen's (weighted) kappa for nominal and ordinal outcome variables (orofacial pain frequency, pain location, jaw function, orofacial symptoms, and changes since last visit) and the intraclass correlation coefficient for linear outcome variables (orofacial pain intensity and functional disability of the jaw).

Results: The 34 included dyads had an overall 'poor' to 'moderate' child-proxy reporting agreement on the questionnaire for the assessment of JIA-related orofacial symptoms. After dividing the children into two age groups, < 13 and ≥ 13 years old, we found substantial agreement on pain frequency and moderate to excellent agreement on pain intensity for the older group. The child-proxy agreement for children aged < 13 years was slight on pain frequency and poor to moderate on pain intensity.

Conclusion: The child-proxy reporting agreement on JIA-related orofacial symptoms is inconsistent. We suggest collecting information from both children and parents, especially when assessing orofacial pain and symptoms in children < 13 years of age.

Objective: To investigate a potentially primary involvement of the facet joints (FJs) in axial spondyloarthritis (axSpA) development, by studying inflammatory and structural magnetic resonance imaging (MRI) and radiographic changes in the sacroiliac joints (SIJs) and lumbar spine, focusing on FJs, in newly diagnosed radiographic axSpA over a 3 year period.

Method: Twenty-four patients (14 male, 10 female; mean ± sd age 33.75 ± 8.6 years) with radiologically and MRI-confirmed axSpA according to modified New York and Assessment of SpondyloArthritis international Society criteria, with a symptom duration < 5.5 years at baseline (t0), were followed up after 3 years (t1) by rheumatologists and radiologists with axSpA MRI experience > 15 years. The Berlin MRI score was extended by an inflammation score of the lumbar FJs. Clinical assessments were performed.

Results: Radiographic SIJs and syndesmophyte progression increased significantly between t0 and t1. MRI progression of the SIJs between t0 and t1 showed increasing bone marrow oedema (BME), significant fat lesion progression, and significant increases in sclerosis and erosion. In the lumbar spine, BME and fat lesions decreased while erosions in the vertebral units (VUs) significantly increased. Facet joint inflammation (FJI) in t0 significantly influenced MRI changes in VU bone proliferation at t1. Biologicals had no effect on MRI changes from t0 to t1.

Conclusions: Structural MRI changes in the SIJs and lumbar VUs, and radiographic axSpA progression, developed significantly within 3 years. MRI-detected lumbar FJI in early disease is associated with MRI signs of VU bone proliferation, indicating a risk of potential ossification.

Objective: Inverse associations between systemic inflammation and cholesterol ('the lipid paradox') have been reported in rheumatoid arthritis (RA) and, in established axial spondyloarthritis (axSpA), but little is known about this relationship in early axSpA, which is the focus of the present study.

Method: In the Swedish part of the SPondyloArthritis Caught Early (SPACE) cohort (patients with chronic back pain for ≥3 months, ≤2 years; age at onset <45 years), serum levels of total cholesterol (TC) and apolipoproteins ApoA1 and ApoB were measured at inclusion, together with parameters reflecting inflammatory disease activity [C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and sacroiliitis by magnetic resonance imaging (MRI) following Assessment of SpondyloArthritis international Society (ASAS) criteria]. All patients included in the analysis either had axSpA based on a high physician's level of confidence or fulfilled the ASAS criteria for axSpA. Associations between lipids/lipoproteins and inflammation were assessed using multivariable linear regression models.

Results: In the 64 patients included, there were inverse associations for CRP with TC, ApoA1, and ApoB in age-sex-adjusted models. The negative associations with CRP remained significant for TC and ApoB in multivariable models adjusted for age, sex, BASDAI, and current smoking (p = 0.048). There were no significant associations for the lipid parameters with BASDAI or inflammation on MRI of the sacroiliac joints.

Conclusion: Inverse associations between systemic inflammation and lipids, particularly TC and ApoB, are present in early axSpA, similar to those shown for other inflammatory joint diseases. These patterns must be considered when including lipids in the evaluation of cardiovascular disease risk.

Objective: To evaluate the cost-effectiveness of longstanding personalized exercise therapy compared with usual care in people with rheumatoid arthritis (RA) and severe functional disability.

Method: In this cost-utility analysis of a randomized controlled trial (n = 215), with 1 year follow-up, the study population comprised individuals with RA and reported severe difficulties in performing basic daily activities. Assessments were at baseline, 12, 26, and 52 weeks, with measurements of costs including medical and non-medical costs as recorded by patients and healthcare providers. Quality-adjusted life-years (QALYs) were estimated using the EuroQol 5 dimensions 5 levels (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ-VAS). Costs and QALY differences were analysed according to the intention-to-treat principle using cost-effectiveness acceptability curves.

Results: The 1 year societal costs were non-significantly in favour of the usual care group, with a small difference of €180 [95% confidence interval (CI) €-4493 to €4852]. The QALYs were non-significantly in favour of the intervention group, by 0.02 according to the EQ-5D-5L (95% CI -0.05 to 0.09) and by 0.04 according to the EQ-VAS (95% CI 0.00 to 0.08). For a willingness-to-pay threshold of €50 000 per QALY, the intervention was the cost-effective strategy with 60% certainty.

Conclusion: This economic evaluation showed no clear economic preference for either group, as the intervention costs were higher in the intervention group, but partly compensated by other cost savings and improved QALYs. Despite severe RA, patients had better clinical outcomes compared with usual care, suggesting no economic reasons to refrain from exercise therapy.

Trial registration number: Netherlands Trial Register NL8235, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8235).