RMD Open最新文献

We report the case of long-term persisting rheumatoid arthritis (RA), treated with CD20-CD19 CAR-T when it became associated with diffuse large B cell lymphoma (DLBCL), resulting in a sustained drug-free remission of the preceding RA, as well as of the subsequent DLBCL that formed the indication of the CAR-T therapy using zamtocabtagene autoleucel, with a 1-year follow-up. According to our best knowledge, this is the first published clinical case report of long-term persisting RA treated with CAR-T cell therapy.

Objective: To assess the presence of mental health disorders in persons with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and Sjögren's disease (SjD) (all: inflammatory rheumatic disease, iRMD) in a population-based cohort.

Methods: Baseline data from 101 601 participants of the German National Cohort (NAKO) were analysed. Self-reported physician's diagnoses of depression and anxiety, the depression scale of the Patient Health Questionnaire (PHQ-9), the Generalised Anxiety Disorder Symptoms Scale (GAD-7), the depression section of the Mini-International Neuropsychiatric Interview (MINI) and cognitive tests on memory and executive functions were analysed. Results of participants with iRMD were compared with participants with osteoarthritis (OA), stratified by age and sex. Cognitive function was described for iRMD and OA using a linear regression model, adjusted for sex and education.

Results: n=3257 participants (3.2%) had an iRMD (2.3% RA, 0.6% AS, 0.5% PsA, 0.2% SLE, 0.1% SjD) and n=24 030 (24%) had OA. Physicians' diagnoses of depression (26% vs 21%), anxiety (15% vs 11%), current depressive (PHQ-9 ≥10: 13% vs 9.0%) and anxiety symptoms (GAD-7 ≥10: 8.6% vs 5.8%) were more frequent in iRMDs compared with OA. In all age groups, women were more often affected than men. Linear regression models showed no differences in neuropsychological test results between iRMD and OA.

Conclusion: Individuals with iRMD frequently experience mental disorders. The study provides an assessment of both self-report and test-based occurrences in this group. Depression and anxiety are more frequent in iRMD compared with OA, whereas levels of cognitive dysfunction were comparable.

Objectives: The widespread adoption of wearables, for example, smartphones and smartwatches in the daily lives of the general population, allows passive monitoring of physiological and behavioural data in the real world. This qualitative study explores the perspective of psoriatic arthritis (PsA) patients towards these so-called digital biomarkers (dBMs).

Methods: As part of a Design Thinking approach, six focus groups were conducted involving 27 PsA patients. The semistructured topic guide included disease activity, coping strategies, care needs, and potential advantages and disadvantages of dBMs. Thematic analysis followed an abductive coding method.

Results: PsA daily permeates patients' lives, both physically and mentally. Participants discussed how their lives are focused on minimising the impact of the disease on their daily routines. Their attempts to gain control over their disease highly depend on trial and error. Flare-ups are related to physiological as well as behavioural micro and macro changes. Understanding these changes could enable the detection of (early) flare. Participants elicited pros and cons of the use of dBMs, discussed their intended use and made practical remarks. This led to three main themes: 'Perceived dBM opportunities', 'Mapping Disease activity' and 'Perceived dBM barriers and pitfalls'.

Conclusion: PsA patients are receptive to dBMs for tracking the disease symptoms. Disease activity is regarded multifaceted and thus, dBMs should include a broad range of features to truly reflect the disease activity status. Reducing the time of trial and error in learning to manage the disease is regarded beneficial. Establishing and maintaining the relationship with their attending physicians is a prerequisite, even if remote patient monitoring becomes an alternative for some physical hospital visits.

Objective: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Adding to studies focused on the role of T cells and macrophages, we sought to investigate the systemic activation of leukocytes in PsA.

Methods: We assessed the activation state of leukocyte populations, including polymorphonuclear neutrophils (PMNs) and monocyte/macrophages, in blood and synovial fluid (SF) by multicolour flow cytometry. We also evaluated the correlation between leukocyte numbers and expression of activation markers with disease activity parameters.

Results: SF PMNs showed an elevated activation state compared with blood PMNs, but a reduced activation state compared with oral PMNs of non-arthritic controls. In vitro stimulation caused SF PMNs to become further activated, demonstrating that they retain a reserve capacity for activation in response to specific triggers. We found significant variability between patients in the expression of SF PMN CD activation markers, indicating a range of possible activation states across patients. However, PMN CD marker expression remained consistent over two sequential visits in a subset of patients, indicating patient-specific distinct inflammatory states during flares. We further found that markers of disease activity increased with elevated SF macrophage numbers. Expression of several CD markers on blood or SF cells, for example, PMN expression of the high-affinity Fc-receptor CD64, correlated with disease activity markers, including pain score and Disease Activity in Psoriatic Arthritis score.

Conclusion: These preliminary findings support a potential role for surface antigens on PMNs and monocytes/macrophages as prognostic or disease activity monitoring tools.

Objective: Treatment strategies of patients with active rheumatoid arthritis (RA) vary within and between countries. While most patients in Germany are treated on an outpatient basis, some are hospitalised (inpatients). In the recently published randomised CORRA (CORRA, CORticoid bridging in Rheumatoid Arthritis) trial, we studied two 12 week glucocorticoid (GC) bridging strategies in patients with early RA comparing high or low GC doses with placebo, followed by an extension phase of 9 months. Here, in this posthoc analysis, we compared 12 week outcomes of patients according to their initial treatment as inpatients or outpatients.

Methods: Inpatients initially spent 2-5 days (short-term) or 14 days (long-term) in one tertiary rheumatology hospital. Outpatients were mostly treated in rheumatology practices. There was no randomisation regarding the initial treatment strategy. The main endpoint of this posthoc analysis was Clinical Disease Activity Index (CDAI) remission at weeks 4, 8 and 12.

Results: Data of 280 outpatients and 95 inpatients could be analysed. Inpatients were more often male, had less cardiovascular comorbidity, but higher baseline CDAI scores and more symptoms of depression compared with outpatients. At weeks 8 and 12, CDAI remission was more frequently observed in inpatients (week 8: 24.7 vs 14.9%; week 12: 30.5 vs 17.3%). These results were confirmed in a multivariable model: OR=2.43 (1.06; 5.55); p=0.035, and OR=2.91 (1.37; 6.14); p=0.005, respectively.

Conclusion: In early active RA, initial inpatient treatment was associated with higher CDAI remission rates at weeks 8 and 12. This may be due to the initially more intense hospital care.

Introduction: Systemic sclerosis (SSc) is a serious life-threatening tissue disease. A significant aspect of its mortality arises from comorbid conditions. Our study aimed at mapping out the prevalence of these comorbidities and their relation to mortality, thus creating a 'comorbidome'.

Methods: In our retrospective, single-centre observational study, we recorded each patient's data, including demographic informations, vital stats and SSc-related organ involvement, along with the presence or absence of 14 predefined comorbidities. We also documented the dates of their initial and most recent visits. To construct survival curves, we used the Kaplan-Meier method, followed by a Cox regression model for multivariate analysis.

Results: Our study involved 400 participants, 74 of whom unfortunately passed away. It is important to note that three specific comorbidities showed significant correlation to mortality: neoplasia, cardiovascular diseases and polypharmacy, as well as two SSc-specific organ involvements (lung and cardiac).

Conclusion: Our research led to the successful creation of the SSc comorbidome. Comorbidities are a major concern for patients suffering from SSc, particularly cardiovascular diseases and neoplasms. Our study highlights the effects of polypharmacy. The resultant comorbidome offers a comprehensive and analytical perspective on this complex issue and underscores the inter-relatedness of the data. Our study, however, was limited by a small sample size. Therefore, to confirm our findings, validation on a larger scale is necessary. This could potentially contribute to the creation of a future mortality scoring tool.

Objectives: To demonstrate efficacy equivalence of CT-P47 and EU-approved reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA).

Methods: This double-blind, phase III study randomised (1:1) patients to receive CT-P47 or r-TCZ (8 mg/kg) every 4 weeks until week 20 during treatment period (TP) 1. Prior to week 24 dosing, patients receiving r-TCZ were randomised (1:1) to continue r-TCZ or switch to CT-P47; patients receiving CT-P47 continued CT-P47 (TP2, 8 mg/kg every 4 weeks until week 48). The dual primary endpoints (for different regulatory requirements) were mean changes from baseline in Disease Activity Score in 28 joints (DAS28; erythrocyte sedimentation rate (ESR)) at week 12 and week 24. Efficacy equivalence was determined if CIs for the treatment difference were within predefined equivalence margins: (95% CI -0.6, 0.6 (analysis of covariance (ANCOVA)) at week 12 or 90% CI -0.6, 0.5 (ANCOVA with multiple imputation) at week 24). Additional efficacy, pharmacokinetic (PK) and safety endpoints, including immunogenicity, were investigated. Findings up to week 32 are presented.

Results: In TP1, 471 patients were randomised (234 CT-P47; 237 r-TCZ). The 95% and 90% CIs for the estimated treatment differences were contained within the predefined equivalence margins; the estimated difference in DAS28-ESR at week 12 was -0.01 (95% CI -0.26, 0.24) and at week 24 was -0.10 (90% CI -0.30, 0.10). Secondary efficacy endpoints, PKs and overall safety were comparable between groups up to week 32.

Conclusions: Efficacy equivalence, alongside comparable PK, safety and immunogenicity profiles, was determined between CT-P47 and r-TCZ in adults with RA, including after switching from r-TCZ to CT-P47.

Objectives: To investigate whether a combination of general health (Visual Analogue Scale (VAS)), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain (VAS/Numerical Rating Scale (NRS)), quality of life (EQ-5D), fatigue (VAS/NRS) and presenteeism (0%-100% productivity loss) could aid as a screening tool to detect active disease in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Methods: RA patients from the tREACH trial and TARA trial (n=683) and PsA patients from the DEPAR cohort (n=525) were included. The association of a deterioration in the aforementioned patient-reported outcome measure (PROM) scores between two consecutive visits and having active disease was assessed. Active disease was defined as a change from disease activity score (DAS) ≤2.4 to DAS >2.4 in RA or Disease Activity Index in Psoriatic Arthritis (DAPSA) ≤14 to DAPSA >14 in PsA. The area under the curve (AUC) of the sum score of deteriorated PROMs was evaluated.

Results: 4594 RA and 1154 PsA visits were evaluated and active disease occurred in 358 (8%) RA and 177 (15%) PsA visits. In both RA and PsA, a deterioration in general health (VAS), HAQ-DI, EQ-5D and pain (VAS/NRS) was significantly associated with active disease. The combination of these PROMs showed acceptable to excellent discriminative ability (RA AUC=0.76, PsA AUC=0.85). If a cut-point of ≥1 deteriorated PROMs is used, 40% of the visits in which RA patients have remission or low disease activity are correctly specified (specificity of 40%), while 10% of visits with active disease are overlooked (sensitivity of 90%). In PsA, these percentages are 41% and 4%, respectively.

Conclusion: A combination of general health, HAQ-DI, EQ-5D and pain could aid as a screening tool for active disease in patients with RA and PsA. These data could help facilitate remote monitoring of RA and PsA patients in the future.

Trial registration numbers: ISRCTN26791028, NTR2754.

Objectives: Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients' quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population.

Methods: Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)).

Results: No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=-0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found.

Conclusion: One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development.

Trial registration number: Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).