BMC Rheumatology最新文献

Background: Canakinumab, an IL-1β inhibitor, has demonstrated long-term efficacy and safety in patients with sJIA, FMF, TRAPS, and MKD/HIDS who experience inadequate disease control with conventional treatments. This non-interventional study aimed to gain insights into canakinumab use and treatment patterns for these diseases in Belgium.

Methods: Between July 1, 2018 and June 30, 2023, this national, non-interventional, retrospective/prospective study enrolled patients aged ≥ 2 years with sJIA, FMF, TRAPS, or MKD/HIDS reimbursed for, and treated with, canakinumab in Belgium. Part 1: retrospective data collection from first canakinumab administration in the initial 6-month reimbursement period until date of study inclusion. Part 2: prospective data collection following study inclusion. Canakinumab treatment and safety data were collected throughout.

Results: At data cut-off, 96 patients (7 sJIA, 70 FMF, 13 TRAPS, 6 MKD/HIDS) were enrolled, of whom 54.2% were female and 87.5% were adults (aged ≥ 18 years). Median age at first canakinumab administration was 34.0 years (20.0, 35.0, 37.0, and 42.0 years in sJIA, FMF, TRAPS, and MKD/HIDS, respectively). Eighteen patients discontinued treatment (3 sJIA, 11 FMF, 4 TRAPS), which was due to lack of efficacy (per investigator's judgment) in 10 (10.4%) patients. Median dose per administration was 289.1 mg in patients with sJIA, and 150.0 mg in patients with FMF, TRAPS, and MKD/HIDS, while median interval between two consecutive administrations was 28.0 days. Thirty-five (36.5%) patients with FMF, TRAPS, or MKD/HIDS received ≥ 1 dose increase (≥ 150 mg). No safety events were reported.

Conclusions: These non-interventional study data highlight that canakinumab treatment patterns are generally aligned with the summary of product characteristics (SmPC) and reimbursement criteria in Belgium and further support the well-tolerated safety profile of canakinumab. However, Belgian reimbursement criteria require long-term glucocorticoids prior to canakinumab therapy; if it were possible to align treatment more closely with EULAR/PReS guidance, which recommends early initiation of anti-IL-1 or anti-IL-6 therapy, glucocorticoid treatment would be limited and improved outcomes for these patients would likely be possible.

Clinical trial number: Not applicable.

Background: Regional variability in the effectiveness and safety of biologic therapies for rheumatoid arthritis (RA) and spondyloarthritis (SpA) underscores the need for comprehensive assessment. The aim of this study was to provide real-world evidence of the effectiveness and the safety of biologic for RA, SpA including psoriatic arthritis, in the daily clinical practice.

Materials and methods: RBSMR registry was a multicenter, cohort study conducted in 10 university departments of rheumatology. The study included RA and SpA patients receiving biotherapy, either as an initiation or ongoing treatment, and investigated for 3 years. The statistical analysis was performed using JAMOVI software (T student test, Mann-Whitney U test, Chi-squared test, Fisher's exact test, Paired T test and Wilcoxon test).

Results: 223 RA and 194 SpA were eligible. After 3 years of follow-up, DAS28 CRP (3.6 ± 1.4 versus 5.8 ± 1.0 at baseline) and ASDAS CRP (1.8[1-2.4] versus 3.5[2.5-4.4] at baseline) significantly improved; 13.8% of RA patients achieved remission based on DAS28 CRP and 20.1% of SpA patients achieved remission based on ASDAS CRP. Overall, 163 and 126 adverse events were reported in RA and SpA patients respectively. Infections were the most frequently reported events with an incidence of 11.8 and 13.4/100 patients-year in RA and SpA respectively. Total incidence rate of tuberculosis was 0.80 patient/100 patients-year.

Conclusions: The RBSMR registry provides real-world insights into the effectiveness of biologics in the practice of rheumatology for RA and SpA patients in Morocco. It underscores the critical need for continued vigilance in monitoring and addressing adverse events, with a particular focus on tuberculosis infection.

Background: Osteoarthritis (OA) is a leading cause of lower limb disability worldwide, imposing significant socioeconomic and personal burden. Thus, many internationally recognised organisations have developed management guidelines for this condition. Among these, the National Institute for Health and Care Excellence (NICE) recommends four first-line approaches to osteoarthritis management: education, exercise, self-management, and weight management. Despite the development of guidelines, adherence to OA management recommendations appears to be suboptimal internationally, and little is known about guideline adherence in South Korea. This study aimed to explore whether research-based physiotherapy interventions for OA in South Korea align with the NICE guidelines.

Methods: A comprehensive search was conducted across multiple Korean and English electronic databases, including the Korea Citation Index (KCI), Korean Studies Information Service System (KISS), MEDLINE, EMBASE, CINAHL, SPORTDiscus SCOPUS, and Google Scholar. Twelve randomized controlled trials conducted in South Korea met the inclusion criteria, with sample sizes ranging from 20 to 60 participants. Participants' mean age ranged from 57 to 75 years, and their Body Mass Index (BMI) varied from 23.00 to 25.68 kg/m². The primary outcome measure was the alignment of interventions with NICE OA guidelines, assessed using a scoring system (0-2 points per study) developed specifically for this review. Additionally, the methodological quality of included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale.

Results: Most studies had poor methodological quality (PEdro scale range: 3-5). Only 42% of the Korean studies aligned with the NICE OA recommendations. Commonly applied interventions were predominantly passive, such as heat therapy, electrotherapy, and kinesiology taping, none of which are recommended by NICE.

Conclusions: A discrepancy was found between research-based physiotherapy interventions for osteoarthritis in South Korea and the therapeutic approaches recommended by the National Institute for Health and Care Excellence guidelines. Factors such as a lack of evidence-based education, research, healthcare funding in South Korea, and cultural health experiences and expectations of the patients may have contributed to these findings. These results could help develop new strategies for improving osteoarthritis management in South Korea.

Background: Patients infected with Hepatitis C Virus (HCV) often present with rheumatic symptoms, but its link to rheumatoid arthritis (RA) remains unclear. The purpose of this cross-sectional study was to investigate whether HCV infection is related to the risk for RA in adults.

Methods: We analyzed data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). HCV infection and RA status were determined through questionnaires. Covariates included gender, age, race, marital status, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), and diabetes status. Multivariate logistic regression and subgroup analyses were used to assess the relationship between HCV infection and RA risk.

Results: In this population-based study involving 5,825 participants aged 18-80 years (including 485 RA patients), we observed a significantly higher prevalence of HCV infection in the RA group compared with non-RA controls. After adjusting for covariates, multivariate logistic regression showed that HCV infection was associated with an increased risk of RA (OR = 1.93; 95%CI = 1.07-3.50, p < 0.05).

Conclusion: This study demonstrates that HCV infection is associated with the risk of RA in adults, underscoring the potential value of HCV screening in RA patients for improved disease management. However, causal interpretation is limited by the cross-sectional design and reliance on self-reported data.

Background: Axial spondyloarthritis (AS) is a chronic inflammatory disease that significantly affects quality of life and imposes a high economic burden on patients due to the cost of biologic disease-modifying antirheumatic drugs (bDMARDs). Dose reduction strategies for bDMARDs may offer a feasible approach to maintaining clinical efficacy while reducing costs. This study aimed to evaluate the clinical effectiveness and cost-efficiency of bDMARD dose reduction in patients with AS and apply machine learning to identify key factors influencing disease control.

Methods: This 12-month prospective study, 368 AS patients receiving ≥ 3 months of full-dose bDMARDs were included. Among 215 initial responders (ASDAS < 2.1), 146 underwent dose reduction while 69 continued full-dose therapy. Clinical outcomes such as C-reactive protein (CRP) levels, the Bath ankylosing spondylitis disease activity index (BASDAI) and ankylosing spondylitis disease activity score (ASDAS) were assessed, along with cost effectiveness using incremental cost effectiveness ratios (ICER). Random forest models were developed to predict the achievement of inactive disease (ASDAS < 1.3) and to identify key predictors.

Results: The dose reduction group demonstrated significantly greater improvements in CRP (-4.05 vs. +2.83 mg/L, p < 0.001), BASDAI (-3.00 vs. +0.89, p < 0.001), and ASDAS (-1.42 vs. +0.09, p < 0.001) compared to the full dose group. A greater proportion of patients in the reduced dose group achieved ASDAS < 1.3 at 12 months (93.2% vs. 33.3%, p < 0.001), with a shorter median time to response (4.20 vs. 4.70 months, p < 0.001). The ICER for achieving ASDAS < 1.3 was favorable (-$6,209.78; 95% CI:-$9,048.35 to-$4,015.78), supporting the cost-effectiveness of dose reduction. A random forest model identified reduced dose strategy, baseline ASDAS, BASDAI, treatment duration, and CRP as key predictors of ASDAS < 1.3, achieving an AUC of 0.845 and F1-score of 0.774.

Conclusions: In this cohort, bDMARD dose reduction was associated with preserved clinical outcomes and lower costs, suggesting it may be a viable strategy for selected patients under close clinical supervision. Predictive modeling provided actionable insights to optimize personalized treatment strategies, balancing efficacy and economic sustainability. These findings support further evaluation of dose reduction strategies, especially in resource-limited settings, to inform potential integration into routine practice.

Background and objective: In recent years, many studies have been conducted on the possible link between rheumatologic diseases and inborn errors of immunity. Rheumatologic diseases may occur as manifestations of an underlying immunodeficiency disorder, and may appear before the more-common infectious manifestations more typically seen in immunodeficiency disorders. In this study, we have attempted to study such symptoms and uncover their relationship with inborn errors of immunity.

Methodology: In this retrospective descriptive-analytical study, 381 cases of IEIs in children that were referred to Mofid Children's Hospital clinic between 2015 and 2019 were evaluated for eligibility to be enrolled in the study. Of these patients, 20 that had confirmed rheumatologic diagnoses were entered into the study. Patients' demographic and medical data, including age at disease onset, age at diagnosis and type of diagnosed rheumatologic and immunodeficiency disorders, parental consanguinity rate, and relevant laboratory findings were retrieved for study and analyzed.

Results: Among 20 eligible patients, half of which were female and half were male, the average age at disease onset, average age at diagnosis of the underlying immunodeficiency disease and average age at diagnosis of the rheumatologic disease were 2.98 ± 1.56, 5.26 ± 3.45 and 3.58 ± 2.97, respectively. JIA made up 10 of the observed rheumatic diseases ("the JIA group"); the remaining 10 patients included SLE (3), FMF (2), juvenile dermatomyositis (2), MCTD (1), GPA (1) and reactive arthritis (1) ("the non-JIA group"). As for the underlying immunodeficiency disorders, CID was seen in 8 patients, followed by CVID (5), XLA (4), SIgAD (2) and CGD (1). The average age at onset of the disease and the average age at diagnosis of the rheumatologic disease were significantly lower in the JIA group than in the non-JIA group (p < 0.05).

Conclusions: A plethora of rheumatologic manifestations may be observed in patients with IEIs; such manifestations should be actively sought out and treated in IEI patients.

Clinical trial number: Not applicable.

Background: Obesity is highly overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity and inferior treatment outcome. We have previously reported in 41 patients with PsA and body mass index (BMI) ≥ 33 kg/m² that weight loss treatment with Very Low Energy Diet (VLED) resulted in a median weight loss of 18,6% and concomitantly a significant improvement in C-reactive protein (CRP) and disease activity at six months (M6). This sub-study analyzes the effects on serum biomarkers associated with inflammation, bone and cartilage metabolism in the same PsA patients and matched controls.

Methods: Patients and controls received VLED treatment (640 kcal/day) during 12-16 weeks depending on baseline (BL) BMI < 40 or ≥ 40 kg/m², followed by an energy restricted diet. Serum was collected at BL and M6, and biomarkers were measured with Magnetic Luminex^® Assays and enzyme-linked immunosorbent assay (ELISA). Nonparametric statistics and paired comparison tests were used.

Results: In the PsA patients, the following proteins were significantly reduced at M6 as compared to BL: hepatocyte growth factor (HGF) (median (first-third quartile) 327.9 (250.3-413.6) pg/mL vs. 271.3 (206.9-331.0) pg/mL, p < 0.01), vascular endothelial growth factor (VEGF) (79.6 (55.9-113.5) pg/mL vs. 69.6 (53.1-105.3) pg/mL, p = 0.01), B-cell activating factor (BAFF) (794.4 (716.4-868.3) pg/mL vs. 674.6 (613.2-790.5) pg/mL, p = 0.01) and cartilage oligomeric matrix protein (COMP) (266.1 (209.9-366.0) ng/mL vs. 217.0 (156.0-272.0) ng/mL, p < 0.01), whereas carboxyterminal telopeptide of type-1 collagen (CTX-1) was significantly increased (268.0 (196.0-378.5) pg/mL vs. 508.0 (350.0-640.0) pg/mL, p < 0.01). Similar results were found in the control group.

Conclusions: Weight loss was associated with reduced levels of serum biomarkers related to inflammation and cartilage degradation, and increased biomarkers for bone resorption. The study supports the strong relationship between obesity, inflammation, bone and cartilage metabolism, identifying BMI as a possible confounder for biomarker levels.

Trial registration: ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.

Background: The early diagnosis of inflammatory rheumatic diseases (IRDs) is of paramount importance in order to prevent irreversible damage to joints and to optimize treatment outcomes. Nevertheless, conventional care pathways frequently entail diagnostic delays spanning several months. Symptom checkers (SCs) have the potential to provide a solution by offering validated symptom assessments, improving triage systems and expediting diagnostic evaluations. The objective of this mixed-methods study is to assess the usability and acceptability of the SC Rheumatic? among individuals with suspected rheumatic diseases.

Methods: A total of 105 individuals with suspected IRDs who were newly presenting at an outpatient rheumatology clinic completed the Rheumatic? symptom checker and an evaluation questionnaire. The questionnaire comprised the System Usability Scale (SUS) and Net Promoter Score (NPS). Additionally, 14 participants were interviewed by telephone in order to gain further insights through the qualitative method.

Results: The Rheumatic? symptom checker received a "good" usability score, with an average SUS of 78 ± 16 (range 0-100). Younger participants reported significantly higher usability scores (p < 0.03). However, the NPS was - 15 (range - 100 to 100), indicating lower acceptability. Qualitative data supported the positive usability ratings but emphasized the need for enhancements to increase user engagement and perceived value, such as a current perceived lack of immediate benefit for many users. Their experience varied in terms of impact, with some patients suggesting an increased awareness of their symptoms while others did not notice any difference.

Conclusion: Rheumatic? demonstrates good usability, particularly among younger users. Interviews revealed valuable suggestions for improvements, which could enhance overall acceptability and user satisfaction. Implementing Rheumatic? could lead to more efficient triage, potentially reducing diagnostic delays and an optimized allocation of resources. Future iterations should prioritize implementation strategies to maximize user impact and benefit.

Clinical trial number: Not applicable.

Background: The identification of responders to methotrexate (MTX) would optimize the therapy of patients with early rheumatoid arthritis (eRA). Our aim was to identify protein biomarkers for the prediction of the response to MTX.

Methods: We analysed patients with eRA (N = 135) from the Swedish Pharmacotherapy (SWEFOT) trial population (Trial registration number: NCT00764725). Baseline serum levels of 177 proteins with an inflammatory signature were profiled via 380 antibodies in a suspension bead array format. Protein levels were analysed for their associations with the achievement of a low 28-joint disease activity score (LDA = DAS28 ≤ 3.2) after 3 months of MTX therapy (primary outcome) or a good response according to the European Alliance of Associations for Rheumatology (EULAR) criteria (secondary outcome).

Results: Multivariable analysis revealed that the serum levels of two of the 177 proteins at baseline, matrix metalloproteinase 7 (MMP-7) and the alpha-chain of fibrinogen (FGA), were significantly different between patients who did and did not achieve LDA at 3 months. Among patients with low versus high levels of either MMP-7 or FGA, 60% versus 24% and 58% versus 22%, respectively, achieved LDA (p < 0.001). Among patients with low levels of both proteins, 79% achieved LDA at 3 months, whereas only 18% of those with high levels of both proteins achieved LDA at 3 months (p < 0.001). The results were similar when a secondary outcome was used.

Conclusions: Low levels of MMP-7 and FGA at baseline were associated with improved clinical outcomes in eRA patients. Validation of these results in another eRA cohort is now warranted, and if confirmed, it may facilitate clinical decision-making regarding whether to start with MTX in monotherapy or more potent alternatives.

Background: Understanding the impact of intensive treatment on pain in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) is crucial to informing the application of evidence-based arthritis pain care. The impact of intensive treatment on inflammatory arthritis pain has received relatively limited attention. We addressed this through a detailed secondary analysis of three trials evaluating varying intensities of disease-modifying anti-rheumatic drug treatment. We considered a range of pain outcomes of clinical relevance to patients, including the achievement of mild endpoint pain scores and clinically-meaningful pain reductions.

Methods: The trials comprised MIPA in PsA, CARDERA in early RA, and TITRATE in established RA. Pain was measured using a 100-mm pain intensity visual analogue scale (VAS). The impact of intensive treatment on (a) patients achieving "mild" endpoint pain intensity scores (of ≤ 34), b) mean changes in pain intensity scores, and (c) patients achieving ≥ 30% reductions in pain intensity scores was evaluated using t-tests, chi-squared tests, and regression models (with the latter adjusting for relevant potential confounding variables).

Results: From MIPA, CARDERA, and TITRATE 128, 379, and 258 patients had endpoint outcome data available and were included in this secondary analysis. In all trials, significantly more patients achieved mild endpoint pain intensity scores with intensive vs. control treatment (MIPA 70% vs. 42%, P = 0.003; CARDERA 71% vs. 56%, P = 0.011; TITRATE 67% vs. 50%, P = 0.008). In the two trials employing the most intensive management strategies (CARDERA; TITRATE) overall reductions in pain scores were significantly greater (6.6 to 6.8 units in adjusted linear regression models), and significantly more achieved ≥ 30% reductions in pain with intensive vs. control treatment (adjusted logistic regression models: CARDERA odds ratio [OR] 1.9, P = 0.009; TITRATE OR 2.2, P = 0.002).

Conclusions: Intensive treatment is an important component of improving pain in patients with active RA and PsA. Our findings support EULAR guidance that optimising disease activity is crucial for pain control. As approximately one third of patients receiving active treatment had moderate/high endpoint pain intensity levels across trials, additional pain management strategies that complement intensive treatment are needed.

Trial registration: Current Controlled Trials CARDERA ISRCTN32484878 (25/10/2000), MIPA ISRCTN54376151 (04/02/2002), and TITRATE ISRCTN70160382 (16/1/2014).