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Objective: We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods: Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON ('continued nintedanib' group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug-drug interaction study and then received nintedanib in SENSCIS-ON ('initiated nintedanib' group).

Results: The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised 247 patients (231 from SENSCIS). Diarrhoea was the most frequent adverse event, reported in 152 (77.2%) and 183 (74.1%) patients in the continued nintedanib and initiated nintedanib groups, respectively. Among patients in the continued and initiated nintedanib groups, respectively, 53 (26.9%) and 148 (59.9%) had ≥1 dose reduction, 72 (36.5%) and 131 (53.0%) had ≥1 treatment interruption and 29 (14.7%) and 72 (29.1%) had adverse events that led to treatment discontinuation. Mean (SE) changes in FVC (mL) at week 148 were -189.1 (29.5) in the continued nintedanib group and -126.4 (26.4) in the initiated nintedanib group.

Conclusion: The safety profile of nintedanib over 148 weeks of SENSCIS-ON was consistent with that reported in SENSCIS. Changes in FVC during SENSCIS and SENSCIS-ON supported a continued effect of nintedanib on slowing the decline in lung function, but showed continued progression of SSc-ILD.

Objectives: Pulmonary involvement is common in systemic lupus erythematosus (SLE), but the relative risk of pulmonary manifestations in SLE versus non-SLE subjects remains unclear. This study aimed to evaluate the risk of pulmonary manifestations in SLE subjects compared with matched controls.

Methods: Using data from the Korean National Health Insurance Service (2009-2017), we identified 6074 individuals aged ≥20 years with newly diagnosed SLE and 60 740 matched controls by age and sex (1:10 ratio) who did not have prior pulmonary manifestations.

Results: Over a mean follow-up of 9.3±2.7 years, the incidence of pulmonary manifestations was 15.2 per 1000 person-years in the SLE cohort and 4.5 per 1000 person-years in the matched cohort. The SLE cohort had a significantly higher risk of pulmonary manifestations (adjusted HR (aHR) 3.26; 95% CI 2.99 to 3.56). The highest risk was observed for pulmonary hypertension (aHR 14.66; 95% CI 9.43 to 22.80), followed by interstitial lung disease (aHR 9.58; 95% CI 7.99 to 11.49), pleural disorders (aHR 3.29; 95% CI 2.84 to 3.81), pulmonary embolism (aHR 2.66; 95% CI 2.06 to 3.43), tuberculosis (aHR 2.35; 95% CI 1.88 to 2.93), acute respiratory distress syndrome and haemorrhage (aHR 1.85; 95% CI 1.51 to 2.25) and lung cancer (aHR 1.41; 95% CI 1.02 to 1.95).

Conclusions: Subjects with SLE have an approximately 3.3-fold higher risk of pulmonary manifestations compared with matched controls. Notably, the risks of pulmonary hypertension and interstitial lung disease are particularly elevated.

Objective: Sjögren's disease (SjD) can have a major impact on sexual functioning, but this topic has received limited attention in research and clinical practice. This qualitative study investigated how SjD affects sexual experience and functioning in both women and men.

Method: Reflexive thematic analysis was performed based on in-depth interviews with patients with SjD. Sexual functioning was measured using the Female Sexual Function Index and International Index of Erectile Function questionnaire.

Results: 11 female and 9 male patients with SjD, aged between 24 and 65 years, were included. According to questionnaire scores, 64% of female and 67% of male participants reported sexual dysfunction. In both sexes, six themes were identified as important in sexual experience and functioning: chronic stress in life, symptoms of SjD (affecting sexual experience), invisible suffering of SjD, impact of illness perception on coping strategies for sexuality-related symptoms, quality of (sexual) partner relationship and taboo of sexuality. These themes interact with each other and together shape the sexual experience.

Conclusion: SjD plays a crucial role in the quality of sexual experience. Many participants reported an unmet need for support, advice and treatment of sexuality-related symptoms related to SjD. The themes generated provide valuable insights into understanding the factors that shape sexual experience and underscore the importance of addressing sexuality-related symptoms as part of holistic care for patients with SjD. Due to the complexity of sexual experience and functioning, future research should focus on the patient as a whole person, and not solely on physical sexual functions.

Objectives: We aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA).

Methods: We conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.1) state at baseline, 6 and 12 months. We focused on cross-sectional methods which impute missing values of an individual at a particular time point based on the available information from other individuals at that time point. We applied nine single and five multiple imputation methods, covering mean, regression and hot deck methods. The performance of each imputation method was evaluated via relative bias and coverage of 95% confidence intervals for the mean ASDAS and the derived proportion of patients in LDA.

Results: Hot deck imputation methods outperformed mean and regression methods, particularly when assessing LDA. Multiple imputation procedures provided better coverage than the corresponding single imputation ones. However, none of the evaluated methods produced unbiased estimates with adequate coverage across all time points, with performance for missing baseline data being worse than for missing follow-up data. Predictive mean and weighted predictive mean hot deck imputation procedures consistently provided results with low bias.

Conclusions: This study contributes to the available methods for imputing disease activity in observational research. Hot deck imputation using predictive mean matching exhibited the highest robustness and is thus our suggested approach.

Background: Patient research partners (PRPs) are people living with a relevant disease who actively contribute to research. Their contribution is beneficial for any research project. Although the inclusion of PRPs in rheumatology research is increasingly recommended, its practical implementation, particularly in translational research, remains limited . Enhancing PRP engagement requires a clear understanding of the necessary steps.

Objective: This study aims to show steps to achieve successful collaboration between PRPs and researchers in clinical and transitional research in rheumatology.

Methods: We established a PRP network by following five main steps: setting up infrastructure, recruitment, training, PRP involvement at an early stage, and ongoing support. We adhered to overall principles of openness, feedback, and regular evaluations to create a respectful and collaborative environment. The initiative was qualitatively assessed via an online questionnaire developed by each six researchers and PRPs.

Results: Communicating our initiative at laboratory open days and to patient associations has enabled to create a network of 66 PRPs. A match-making tool was introduced to allocate interested PRPs with a project request. This led to PRP involvement in 15 projects, including 9 in translational research. Two PRP-coordinators provided support including glossaries and educational courses .

Conclusion: Our initiative outlines five essential steps for establishing PRP collaboration in rheumatology research, including translational research. This approach benefited both PRPs and researchers and might serve as a guide for other centres.

Objectives: Anatomical variation of the sacroiliac (SI) joints is common and specific variants are associated with erosions and bone marrow oedema on imaging. Our investigation aims to evaluate whether anatomical variations influence the clinical presentation of axial spondyloarthritis (axSpA).

Methods: In this propensity score matched post hoc analysis documented clinical data from four prospective clinical cohorts was assessed. Classification of back pain as inflammatory (=IBP), human leucocyte antigen-B27 positivity, family history, disease activity according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), symptom duration, elevated acute phase reactants, peripheral and extramusculoskeletal manifestations were evaluated. Statistical analyses were done using (generalised) linear models, t-tests, χ² tests and analysis of variances. Multiple testing was corrected according to Bonferroni.

Results: A total of 165 patients (86 women) were included. Atypical SI joints, defined by the presence of accessory joint facets, iliosacral complex or crescent-shaped ilii on MRI, were identified in 61 out of 165 patients with axSpA. Disease activity, assessed by BASDAI and symptom duration were similar in both groups (adjusted ß=-0.118 (95% CI -0.713, 0.476), p=0.696 and 120.0 (107.4) vs 116.5 (98.3) months, p=0.838, respectively). There was no significant difference in IBP between the groups (adjusted OR=0.614 (95% CI 0.274, 1.377), p=0.236). Sex-stratified analysis revealed no statistically significant results.

Conclusion: Our analysis suggests that clinical phenotypes do not significantly differ between patients with axSpA with and without atypical joints.

Objective: Ultrasonography is crucial for diagnosing giant cell arteritis (GCA); however, training opportunities are rare. This study tested the reliability of ultrasonography findings and measurements of the intima-media thickness (IMT) among ultrasonography experts by using phantoms of the axillary (AA) and temporal arteries (TA) created with high-resolution 3D printing.

Methods: Twenty-eight participants from 12 European countries received eight sets of phantoms of the AA and the superficial TA (including common, frontal and parietal branches), which were examined in a blinded fashion according to a predefined protocol and evaluated based on Outcome Measures in Rheumatology (OMERACT) GCA ultrasound definitions. Due to difficulties with the delineation of the intima-media complex, the parietal branch of the phantoms was modified, and a second round was conducted. The IMT was measured, and phantoms were classified as normal or vasculitic.

Results: In both rounds, the phantoms were correctly classified as normal/abnormal in >81% of cases yielding a Fleiss' kappa of 0.80 (95% CI 0.78 to 0.81) in round 1 and 0.74 (95% CI 0.72 to 0.75) in round 2. IMT measurements revealed an intraclass correlation coefficient (ICC 1.1) of 0.98 (95% CI 0.98 to 0.99) in both rounds. Intrarater reliability was good with a median Cohens Kappa of 0.83 and median ICC of 0.78.

Conclusion: The study demonstrated high reliability among ultrasound experts in applying the OMERACT ultrasound definitions for GCA and in measuring the IMT using a 3D-printed phantom of the AA and TA. This phantom could assist clinicians in training to assess the large arteries of patients with suspected or established GCA.

Objective: Anti-SS-B antibodies are often associated with anti-SS-A in Sjögren's disease. Compared to anti-SS-A antibody positivity, the significance of the immunological profile anti-SS-B positive/anti-SS-A negative remains controversial. We aimed to evaluate the prevalence and diagnostic significance of isolated anti-SS-B antibodies.

Methods: We conducted a retrospective study across three hospitals of the Assistance Publique-Hôpitaux de Paris. Patients with anti-SS-B positivity were identified using ELISA, addressable laser beam immunoassay (ALBIA) and immunodot assays. They were retained if anti-SS-B was positive in two techniques and anti-SS-A was absent. Clinical, biological and immunological data were extracted and presented in a descriptive analysis.

Results: A total of 80 540 requests for anti-SS-B antibody testing were carried out over a period of 7.9 years. Anti-SS-B positivity was found in 1693 patients. Among them, 335 (19.8%) patients had isolated anti-SS-B in ELISA/ALBIA. Immunodot was performed in 186 of them and confirmed anti-SS-B positivity in 61 patients (3.6% of anti-SS-B positivity). 24 patients (39.3%) presented with a history of various autoimmune or autoinflammatory diseases and only 6 were diagnosed with a new connective tissue disease. After a median follow-up of 26 months, only two new diagnoses were made.

Conclusion: Anti-SS-B without anti-SS-A is exceedingly rare when accurately identified by a rigorous immunological approach. The initial anti-SS-B positivity does not correlate with a specific condition, both at the time of initial identification and after a 26-month follow-up period. This supports the fact that isolated anti-SS-B has no diagnostic or prognostic value.

Objective: The antibody response against Porphyromonas gingivalis (Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the Pg virulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis.

Methods: At-risk individuals were included in a prospective study (Risk-RA) based on a positive anti-cyclic citrullinated peptide 2 (CCP2) antibody test, and having musculoskeletal complaints but no signs of arthritis. Study participants were followed for ≥3 years (arthritis-free, n=165) or until arthritis onset (progressors, n=95). Anti-Rgp IgG was measured in Risk-RA (260 baseline and 247 follow-up samples) and healthy controls (n=126); anti-CCP2 IgG was measured in Risk-RA (254 baseline samples). Data were analysed in GraphPad Prism and R using log-transformed antibody levels.

Results: 53% of Risk-RA and 26% of controls, p=0.003, were anti-Rgp IgG positive at baseline, with higher levels in Risk-RA compared with controls, p<0.0001. No changes in anti-Rgp IgG levels were observed during follow-up. The anti-Rgp IgG response at baseline did not associate with the development of arthritis; Cox-regression showed an HR of 0.95 (CI 0.80 to 1.13, p=0.6) for anti-Rgp IgG levels, and 0.82 (CI 0.55 to 1.23, p=0.3) for anti-Rgp IgG positivity.

Conclusions: Antibodies against the oral bacterium Pg are elevated during the RA-risk phase, both in individuals progressing to arthritis and in individuals remaining arthritis-free. Hence, Pg infection can be linked to the presence of RA-specific autoimmunity, ACPA, and musculoskeletal symptoms, but not to further development of arthritis in this at-risk population.

Objective: Assess long-term safety, tolerability and efficacy of bimekizumab in ankylosing spondylitis (radiographic axial spondyloarthritis (r-axSpA)).

Methods: Patients with active r-axSpA completing the dose-ranging 48-week randomised controlled trial could enrol in the open-label extension, where patients received bimekizumab 160 mg every 4 weeks. Safety (exposure-adjusted incidence rates/100 patient-years (EAIRs)) and efficacy outcomes (binary: non-responder imputation (NRI) and observed case (OC); continuous: multiple imputation (MI)) are presented through 256 weeks.

Results: From Weeks 0-256, 289/303 (95.4%) patients had ≥1 treatment-emergent adverse event (TEAE); most frequent were nasopharyngitis (21.8%) and upper respiratory tract infection (14.5%). The EAIR of fungal infections was 7.4 (Candida infections: 2.6; oral candidiasis: 2.2); none systemic. EAIR of serious infections was 1.4; no active tuberculosis was reported. Active inflammatory bowel disease and anterior uveitis EAIRs were 0.8 and 0.7, respectively. 202/303 (66.7%) patients completed Week 256. 42 (13.9%) patients discontinued treatment due to TEAEs.Efficacy at Week 48 was maintained for 5 years. At Week 256, NRI analysis showed 49.7% (OC: 73.1%) and 41.6% (OC: 71.1%) of patients achieved Assessment of SpondyloArthritis International Society 40% (ASAS40) response and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity, respectively. Mean (SE; MI) ASDAS improved from 3.9 (0.1) at baseline to 2.1 (0.1) at Week 48, which was maintained to Week 256. Improvements in pain, fatigue, physical function and health-related quality of life were sustained.

Conclusions: The safety profile of bimekizumab after 5 years of treatment remained consistent with previous reports, with no new safety signals identified. 5-year efficacy was sustained in this r-axSpA population following robust disease control achieved at Week 48.

Trial registration numbers: NCT02963506; NCT03355573.