Rheumatology and Therapy最新文献

The transition from a comorbidity-based to a multimorbidity-focused to ultimately a network medicine approach in people with rheumatic diseases might mark a significant shift in how we understand and manage these complex conditions. Multimorbidity expands on the concept of comorbidity by encompassing the presence of multiple diseases, which results in further individual and societal impacts. This approach, while valuable, often leads to fragmented care focused on individual diseases rather than the patient as a whole.Network medicine, on the other hand, offers a more integrated perspective. It is an emerging concept that leverages the understanding of biologic networks and their interactions within the human body to gain insights into disease mechanisms. In the context of rheumatic diseases, network medicine involves examining how different diseases interconnect and influence each other through shared pathways, genetic factors, and molecular mechanisms.This paradigm shift allows for a more holistic understanding in how we manage rheumatic diseases. For instance, rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are not just a collection of symptoms affecting various organs but are also interconnected through underlying systemic inflammatory processes, immune system dysregulation, and genetic predispositions.

Current literature regarding cancer risk in rheumatic and musculoskeletal diseases (RMDs) is particularly poor and controversial, even though the incidence of malignancy in some patients with RMDs is considered to be increased compared with the general population. Malignancy may be a major comorbidity in subjects with spondyloarthritis (SpA) as the result of multifactorial mechanisms, from disease pathogenesis to the iatrogenic effect of immunomodulating drugs. Several recommendations for screening and management of cancer risk have been developed in recent years with the aim of improving the different outcomes in these patients. The goal of this narrative review is to provide an overview of the currently available evidence on the risk of malignancy connected with RMDs and examine the association of SpA with cancer and the potential impact of its treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs on development of malignancy.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited. Participants received a single intra-articular LOR or placebo (PBO) injection at their parent-trial baseline. The primary outcome was the comparative incidence of serious adverse events (SAEs), with AEs and similar safety measures comprising secondary outcomes. A post hoc baseline-adjusted analysis of covariance (ANCOVA) compared changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function subscores and medial joint space width (JSW) between LOR 0.07 mg and PBO groups in a subpopulation of participants with unilateral knee pain and widespread pain low enough to allow participants to differentiate their target knee pain.

Results: The safety analysis set for the extension study included 495 LOR-treated and 208 control participants, with 409 (82.6%) and 175 (84.1%) remaining at study close, respectively. There were 68 SAEs reported in 38 (5.4%) patients; none were considered treatment-related by investigators. The incidence of AEs was similar between groups. In the post hoc subgroup efficacy analyses, LOR 0.07 mg demonstrated greater mean improvements from baseline compared with PBO in WOMAC pain and function scores out to 12 months post-injection. No between-group differences in medial JSW were observed out to 18 months.

Conclusions: LOR appeared generally safe and well tolerated. Efficacy analyses on the subset of completer patients demonstrated durable symptom improvements in WOMAC pain and function for at least 12 months compared to PBO after a single injection of LOR.

Clinical trial registration number: NCT02951026.

Introduction: Ozoralizumab (OZR) is a novel tumor necrosis factor (TNF) inhibitor that was launched in Japan for treating patients with rheumatoid arthritis (RA) who have had an inadequate response to existing therapies. This post-hoc analysis aimed to compare the efficacy of OZR administered without methotrexate (MTX) with placebo or OZR administration in combination with MTX.

Methods: We analyzed the OZR group (30 mg) in the NATSUZORA trial (non-MTX, open trial) (OZR group; n = 94) and the placebo group (MTX group; n = 75) and the 30-mg OZR group (OZR + MTX group; n = 152) in the OHZORA trial (combined MTX, double-blind trial), and the covariates were adjusted by propensity score matching. Subsequently, the American College of Rheumatology (ACR) 20/50/70 response rates from baseline to 24 or 52 weeks were compared. Furthermore, to compare longitudinal data on disease activity indicators, a mixed-effects model for repeated-measures analyses was used.

Results: Comparing the OZR and MTX groups, 52 patients were matched in each group. The OZR group showed improvements in the ACR20 (OZR group, 67.3% vs. MTX group, 34.6%, p = 0.001), ACR50 (51.9% vs. 17.3%, p < 0.001), and ACR70 (26.9% vs. 11.5%, p = 0.047) response rates compared to those in the MTX group. Comparing the OZR and OZR + MTX groups, 77 patients were matched in each group. No significant difference was observed in the ACR20 response rate (OZR group, 58.4% vs. OZR + MTX group, 70.1%, p = 0.130). However, the OZR + MTX group showed higher ACR50 (44.2% vs. 62.3%, p = 0.024) and ACR70 (29.9% vs. 45.5%, p = 0.046) response rates.

Conclusion: OZR administration without MTX was associated with an improvement in the signs and symptoms of RA compared to placebo administration (continuation of MTX monotherapy). OZR and MTX administration showed better efficacy than OZR administration alone.

Introduction: Prescribable digital health applications (DiGAs) present scalable solutions to improve patient self-management in rheumatology, however real-world evidence is scarce. Therefore, we aimed to assess the effectiveness, usage, and usability of DiGAs prescribed by rheumatologists, as well as patient satisfaction.

Methods: The DiGAReal registry includes adult patients with rheumatic conditions who received a DiGA prescription. Data at baseline (T0) and the 3-month follow-up (T1) were collected through electronic questionnaires. Study outcomes included DiGA-specific outcome assessments as well as generic outcome assessments, including the Patient Global Impression of Change (PGIC), Patient Activation Measure (PAM®), and the German Telehealth Usability and Utility Short Questionnaire (TUUSQ). Changes between T0 and T1 were analyzed using descriptive statistics and paired tests.

Results: A total of 191 patients were included between June 2022 and April 2023. Of these, 127 completed the 3-month follow-up, and 114 reported using the prescribed DiGA, with 66% reporting weekly use and 15% completing the full DiGA program. The most commonly prescribed DiGAs targeted pain management (53%). Symptom improvement was reported by 51% of patients using a DiGA, with significant reductions in exhaustion levels (p = 0.03). Significant DiGA-specific improvements were observed for DiGAs addressing back pain (p = 0.05) and insomnia (p = 0.006). However, no overall significant changes were detected in patient activation, health literacy, pain, overall health, or disease activity. Back pain and weight management DiGAs were the most effective, frequently used, and best-rated DiGAs, with symptom improvements reported by 50% to 82% of patients.

Conclusion: The findings suggest that DiGAs can improve symptom management in rheumatic patients, especially for conditions like back pain and weight control. Further real-world evidence is needed and may support value-based digital health efforts and reimbursement frameworks.

Introduction: Celiac disease (CD) affects the small intestine, leading to a progressive disappearance of intestinal villi, and can be found in association with several other autoimmune and inflammatory conditions. The main objective of this study was to determine the prevalence and the clinical significance of anti-transglutaminase and anti-endomysium antibodies in patients diagnosed with early rheumatoid arthritis (RA) and spondyloarthritis (SpA).

Methods: We measured anti-transglutaminase and anti-endomysium antibodies in biobanked serum samples at inclusion in two French prospective multicenter cohorts of patients with suspected early rheumatoid arthritis (ESPOIR, n = 713) and spondyloarthritis (DESIR, n = 709). Results were compared with the clinical, laboratory, and radiographic findings obtained in patients during a 10-year follow-up period.

Results: In the DESIR cohort, anti-transglutaminase antibodies were evidenced at low levels (less than three times the upper limit of normal) in 2/709 (0.42%) patients and anti-endomysium antibodies in 0/709 (0%). In the ESPOIR cohort, anti-transglutaminase antibodies were evidenced in 6/713 (0.84%) patients and anti-endomysium antibodies in 1/713 (0.14%). Only the latter patient was confirmed to have celiac disease. Interestingly, this patient was ultimately diagnosed with Sjögren's disease, an autoimmune condition known to be associated with an increased risk of celiac disease.

Conclusion: The very low identified prevalence of anti-transglutaminase and anti-endomysium antibodies suggests a negligible risk of celiac disease in patients with early-stage RA or SpA, which are among the most common inflammatory rheumatic conditions. Consequently, routine screening for celiac disease via these antibodies in patients presenting with early inflammatory rheumatic conditions should not be performed except in case of clinical suspicion of celiac disease.

Introduction: Axial spondyloarthritis (axSpA) is a chronic inflammatory condition associated with considerable pain and impaired health-related quality of life (HRQoL) for affected patients. Despite the documented increase in healthcare resource utilization (HRU) related to axSpA, few studies have explored the impact of diagnostic delays on these outcomes. This study sought to determine the association between diagnostic delay of axial spondyloarthritis (axSpA) and costs in the 3 years after diagnosis.

Methods: This is a retrospective, observational study based on routine follow-up data from adult patients with confirmed axSpA diagnosis in three tertiary Spanish hospitals. Sociodemographic and clinical variables were collected at diagnosis. Direct and indirect healthcare costs were estimated from healthcare resource use (HRU) and productivity losses. The correlation between diagnostic delay and total healthcare costs was analyzed.

Results: Eighty-two patients (62.2% men; mean age: 39.3 years at diagnosis) were included, mostly with radiographic axSpA (r-axSpA) (67.1%). The mean (standard deviation, SD) diagnostic delay was 10.1 (9.3) years, with a median (interquartile range, IQR) of 5.4 (2.3, 17.2) years. The mean total healthcare cost per patient accumulated over 3 years was €25,812.6 (direct: €16,384.7; indirect: €9427.9). Patients with longer diagnostic delay (> 5.4 years) had 57% higher total healthcare cost (€31,717.7 vs. €20,188.7, p = 0.029) and higher disease activity at diagnosis (BASDAI score 4.7 vs. 3.4, p = 0.007) and after 3 years (3.9 vs. 2.9, p = 0.042) compared to those with shorter delay (≤ 5.4 years).

Conclusions: The diagnostic delay in axSpA remains high and is associated with an increase in healthcare costs post-diagnosis. Actions to reduce diagnostic delay should be prioritized by healthcare systems to potentially improve outcomes and reduce long-term costs.