BMC Rheumatology最新文献

Background and aim: Spondyloarthritides (SpA) are common entities of the inflammatory rheumatic type. There are still 3 relevant problems in everyday clinical practice: early disease detection, cardiovascular risk assessment, and less so, disease activity measurement. Metabolomics allows the quantification of a large number of small-molecule substances from biological samples.

Methods: The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1973 until 2024.

Results: Finally, 14 analyses were identified. Most studies have evaluated patients with established disease. Some studies were able to un-mask metabolomic characteristics of certain forms of SpA. Approaches that utilize an integrative view of several metabolites in combination with general patient characteristics appear to be quite promising. Such approaches are suitable, for example, for assessing activity in psoriatic arthritis (PsA) or evaluating cardiovascular risk in individuals with psoriatic disease.

Conclusions: Metabolomics are helpful in identifying new diagnostic and predictive parameters in SpA, so far mainly in PsA. An almost consistent limitation of the studies to date is the inclusion of patients with already manifest disease.

Objective: Anifrolumab, a monoclonal antibody targeting the type I interferon-α receptor, has been approved for the treatment of moderate-to-severe systemic lupus erythematosus (SLE). This study aimed to assess its safety profile in real-world settings.

Methods: This study analyzed all adverse events reports involving anifrolumab as the primary suspected drug from the quarter of 2021 to the third quarter of 2024 in the FDA Adverse Event Reporting System database. Disproportionality analyses were conducted using reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network. The temporal risk of AEs was modeled using the Weibull distribution.

Results: The most frequently reported AEs included upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, cough, hypersensitivity, and nasopharyngitis. Potential adverse reactions not listed in the product label were identified, such as dyspnea, pyrexia, vomiting, pruritus, dizziness, abnormal feeling, chest pain, urticaria, alopecia, increased blood pressure, swelling, and migraine. AEs primarily occurred within the initial month of treatment.

Conclusion: This study provides valuable safety data on the real-world application of anifrolumab, confirming known AEs and revealing additional potential risks. The findings offer critical safety information for clinicians prescribing anifrolumab for the treatment of SLE, aiding in the optimization of patient management and treatment decision-making.

Background: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). However, MTX use is associated with gastrointestinal adverse effects in a number of patients. Early detection of MTX intolerance could help modify the treatment strategy, thereby ensuring patient compliance and response. In the present study we aimed to identify the prevalence of MTX intolerance, and associated risk factors in a cohort of Indian RA patients receiving oral MTX therapy.

Methods: In this cross- sectional study, RA patients who were in regular use of oral or subcutaneous MTX for a minimum duration of three months were included. The participants were evaluated based on their responses to the methotrexate intolerance severity score (MISS) questionnaire. Patients with a MISS score ≥ 6 were considered MTX intolerant. Demographic data encompassing the patient's age, sex, diet, MTX dosage, duration of use, route of administration, other medication, and disease activity assessed using the DAS-28 CRP was collected using a standardized patient history sheet.

Results: Out of 200 adult RA patients, 86% were females with an average age of 49.25 ± 11.89 years, and the average duration of MTX use was 46.16 ± 53.40 months. A high prevalence of MTX intolerance (34.5%) was observed in RA patients. Nausea (85.5%) followed by abdominal discomfort (59.42%) were the most prevalent symptoms in intolerant patients. Furthermore, using multivariate analysis, we observed a positive association of MTX intolerance with female gender, disease severity, and MTX dose.

Conclusion: Although MTX is the one of the most commonly used medication for the treatment of RA, there is significant intolerance to this drug among adult RA patients. The symptoms observed not only occur after MTX intake but are also present before intake (anticipatory) and while thinking of taking MTX (associative). Our data indicates that a MTX dose of 15 mg/week or greater may be associated with intolerance. There is a need to objectively monitor RA patients to identify MTX intolerance early on to ensure mitigation steps for effective treatment response.

Background: Rituximab is known as an efficacious drug for the treatment of Rheumatoid Arthritis (RA). The original administration schedule consisted of two infusions of 1000 mg with a 2-week interval. We aimed to explore the long-term effectiveness of rituximab in daily clinical practice in patients with RA.

Methods: Data of patients with RA treated with rituximab in a tertiary university hospital (2006-2019) were retrospectively collected from rituximab initiation until December 1st 2019 or rituximab discontinuation, whichever came first. Rituximab retreatment was based on a treat-to-target-approach guided by a 28-joint disease activity score (DAS28) ≥ 3.2, as dictated by national reimbursement criteria. Rituximab retention rate was investigated using a Kaplan-Meier survival curve.

Results: We collected data of 104 patients (59% female, 94% RF/ACPA-seropositive). At rituximab initiation, patients had a mean ± SD age of 58 ± 12 years and median disease duration of 12 (IQR 5-17) years. Patients were followed for a median of 40 (IQR 14-80) months and received a median of 3 (IQR 2-6) rituximab cycles. In total, 9% (9/104) patients discontinued rituximab and 14% (15/104) were treated with a reduced dose. Inherent to the retreatment strategy, disease activity fluctuated with a DAS28-increase before every new rituximab administration. Similar fluctuations were noticed for patient and physician reported outcomes. Proportion of patients continuing rituximab after three years was 94% (95% CI 89% - 99%).

Conclusions: Although rituximab can be considered as an efficacious drug for RA treatment in daily practice, fluctuations in disease activity were noticed related to the retreatment approach, accompanied by impaired patient's wellbeing.

Trial registration: Not applicable.

Objectives: To quantify the influence of lifestyle factors on tumour necrosis factor inhibitor (TNFi) treatment response, in axial spondyloarthritis (axSpA).

Methods: Data on biologics-naïve adults with axSpA were captured from European rheumatology registries. Information on lifestyle factors (smoking, overweight/obesity, and/or alcohol consumption) were identified ± 30 days of commencing their first TNFi. Treatment response (BASDAI-50, ASDAS or ASAS response criteria) was determined at 3 and 12 months. In separate models, the relationship between treatment response and baseline smoking, BMI and alcohol was assessed using logistic regression, adjusted for age, sex, country, calendar year of treatment initiation, disease duration and baseline disease activity.

Results: From 14 registries, 14,885 patients were included. Of those with available data, 29% were current smokers, 49% current drinkers, 37% were overweight and 21% were obese. At 12 months, smokers were less likely to achieve BASDAI-50 treatment response compared to non-smokers (adjusted odds ratio: 0.77; 95%CI: 0.68-0.86). A similar effect was observed among overweight (0.76; 0.66-0.87) or obese patients (0.53; 0.45-0.63). In contrast, alcohol drinkers experienced a seemingly beneficial effect (1.47; 1.16-1.87). These associations were also observed with other measures of treatment response and were robust to further adjustment for clinical characteristics.

Conclusion: Smoking and high BMI decrease the odds of bDMARD treatment success in axSpA. Rheumatologists should consider referral to smoking cessation and/or weight management interventions at the time of commencing therapy, to enhance treatment response. The relationship between alcohol and treatment response is unlikely to be causal and warrants further investigation.

Background: Rheumatoid arthritis (RA) is a progressive autoimmune disease. During complex therapy, vitamin D supplementation could have an immunomodulatory effect and improve disease activity.

Aim: The aim of this study was to investigate the effects of vitamin D supplementation on laboratory parameters and the disease course among patients with RA.

Methods: This prospective, randomized, parallel-group, double-blind study with a follow-up period of 6 months aimed to investigate the effects of 4000 IU/day vitamin D on visual analogue scale (VAS) and disease activity score-28 (DAS-28) scores among RA patients treated at the Rheumatology Clinic of the University Clinical Centre of Kosova. The study included 100 RA patients (82 women and 18 men) who were divided into two groups: patients with vitamin D supplementation and patients without vitamin D supplementation.

Results: Our results revealed no significant differences in baseline clinical or laboratory parameters between the study groups. At the beginning of the study, to ensure homogeneity between the study groups, we compared inflammatory mediators between groups. We found no significant differences in the IL6 (H statistic of 1.79 for p.180), IL17 (H statistic of 0.015 for p.902), TNF (H statistic of 1.15 for p.284), ESR (H statistic of 0.085 for p.771) or CRP (H statistic of 1.45 for p.229) levels between the two groups. After six months of supplementation therapy, the vitamin D group showed significant differences in pain reduction (VAS score, U'=2245.5; P < 0.0001) and disease activity (DAS28 score, U'=2285.5; P < 0.0001).

Conclusions: Supplementation with 4000 IU/day of vitamin D can potentially improve disease activity and pain management among RA patients after six months. However, further research is needed with a focus on longer patient follow-up periods to determine the long-term benefits of vitamin D in RA patients.

Trial registration: ID NCT06716476, Date of Registration 04.12.2024.

Background: The incidence of autoimmune diseases in cold environments has been a topic of interest due to the observed geographical patterns and potential environmental influences on disease development. We aimed to investigate the prevalence of five main autoimmune diseases in 201 countries according to average annual temperatures.

Methods: Linear regression analysis was performed for 201 countries by analyzing average annual temperatures and age-standardized rates (prevalence) of five autoimmune diseases: alopecia areata, diabetes mellitus (DM) type 1, inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis (RA). A systematic review was also conducted to evaluate whether the observed correlations were supported by published original studies.

Results: The linear regression analysis showed a strong correlation between average annual temperatures and age-standardized prevalence rates (p < 0.0001) across 201 countries. The systematic review analysis indicated that certain autoimmune diseases, such as DM type 1, RA, psoriasis and IBD, demonstrate robust associations with geographic and climatic factors. However, there were no available published data for alopecia areata.

Conclusions: These findings underscore the complexity of interactions between environmental, and genetic factors in the development of autoimmune diseases. Further investigation is required to better understand the association between temperature and prevalence of autoimmune diseases and to identify any additional epidemiological factors that contribute to autoimmune pathogenesis.

Background: Janus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-recognise evolving epitopes of new viral variants, as evidenced by the SARS-CoV-2 vaccination. Consequently, we investigated the de novo T-cell response to SARS-CoV-2 vaccination in patients with rheumatic diseases undergoing treatment with JAK inhibitors.

Methods: Cross-sectional study, conducted in an outpatient department. Patients with rheumatic disease who had received two vaccinations against SARS-CoV-2 while under therapy with JAKi (n = 22) or tumour necrosis factor-blocking biologicals (TNFi) (control group n = 16) were recruited. To evaluate the vaccine-induced T cell response, the patients' PBMCs were stimulated with SARS-CoV-2 spike protein peptides. The percentage of CD4⁺ T cells responding specifically to this stimulation by producing IFNγ was then measured using intracellular cytokine staining and flow cytometry. In addition antibody response to vaccination was assessed.

Results: A specific T cell response was detected in 11 out of 22 (50.0%) of patients in the JAKi cohort, compared to 13 out of 16 (81.3%) of the TNFi cohort (p = 0.088). Patients on JAKi had a lower percentage of CD4⁺ T cells responding to stimulation with SARS-CoV-2 spike peptides than patients on TNFi (p = 0.021). The proportion of patients with an antibody response and absolute anti-spike IgG levels did not significantly differ between the cohorts.

Conclusions: Patients on JAKi exhibited a compromised de novo T cell response to SARS-CoV-2 vaccination compared to TNFi patients. There is a need for further research on the effect of JAKi on T cell responses to vaccination.

Background: It is well-documented that systemic lupus erythematosus (SLE) is associated with asthma. However, the causal relationship between SLE and asthma, and the potential mediator need to be explained. This study aims to confirm the cause-and-effect relationship between SLE and asthma, and evaluate the mediation effect of lipid in European ancestry.

Methods: A Two-sample Mendelian randomization (MR) study was applied to analyze the causal relationships between SLE and asthma. A two-step MR design was used to explore whether low-density lipoprotein cholesterol (LDL-C) mediates the causal pathway from SLE to asthma outcome. Cochran's Q statistic methods and MR-Egger regression were used to assess heterogeneity and pleiotropy. Leave-one-out (LOO) sensitivity test was adopted to estimate the effect of removing one of the selected individual SNPs on the overall results. Funnel and forest plots were also conducted to detect the pleiotropy directly.

Results: SLE was significantly associated with higher asthma risk according to inverse-variance weighted (IVW) method [OR (95%CI): 1.093 (1.024-1.166)] (P = 0.007), MR Egger method [OR (95%CI): 1.192 (1.077-1.319)] (P = 0.028) and Maximum likelihood [OR (95%CI): 1.094 (1.036-1.155)] (P = 0.001), which were robust across adequate sensitivity analysis. On the contrary, asthma has no causal relationship with SLE. In addition, LDL-C may mediate a proportion of 6.15% of the total effect between SLE and asthma.

Conclusion: This study demonstrates that patients with SLE may have a higher risk of developing asthma, which may be mediated by LDL-C. Understanding this relationship provides insight into potential mechanisms underlying asthma development in SLE patients and offers a foundation for developing targeted treatment strategies to manage these risks effectively.

Background: Many outcomes relevant to rheumatoid arthritis are measured as continuous variables. Judging whether the results of those measurements are clinically significant requires determining the minimal important difference (MID) estimate. Therefore, valid MID estimate(s) are essential for the purposes of clinical decision-making and developing clinical recommendations. Our objective is to present the MID estimates for instruments used to measure outcomes in rheumatoid arthritis studies.

Methods: We conducted a scoping review. We included original research reports on MID of instruments used to measure outcomes in rheumatoid arthritis, using distribution- or anchor-based methods. We excluded conference abstracts. We searched MEDLINE (OVID) and EMBASE (OVID) databases on January 6, 2025 and scanned the reference lists of included studies and of identified relevant systematic reviews. Reviewers screened the titles and abstracts and full-texts, then abstracted data in duplicate and independently. They resolved disagreements by discussion or by consulting a third reviewer. We summarized the data narratively and in tabular formats.

Results: We identified 35 eligible studies reporting on a total of 144 MID estimates for 72 instruments used in rheumatoid arthritis. The most common constructs measured were physical function (26%), disease activity (18%), health status (17%) and fatigue (14%). The majority of measurement instruments were generic (60%). The most common instrument with MID estimates was the Health Assessment Questionnaire Disability Index (7%). The majority of MID estimates were calculated using anchor-based methods (72%). We did not critically appraise the included studies.

Conclusions: We identified the MID estimates for a substantive number of measurement instruments used in rheumatoid arthritis. There was considerable variability in the findings for the same instrument within and across studies.