Open Access Rheumatology-Research and Reviews最新文献

Purpose: To evaluate the characteristics, efficacy, and retention of tofacitinib monotherapy in patients with rheumatoid arthritis using data from randomized controlled trials (RCTs) and real-world data (RWD).

Patients and methods: Three patient groups receiving tofacitinib 5 mg twice daily (BID) monotherapy were defined for post hoc RCT/long-term extension (LTE) analyses: (1) disease-modifying antirheumatic drug (DMARD)-inadequate responder patients from phase 3/3b/4 RCTs; (2) methotrexate-naïve patients from a phase 3 RCT; and (3) index study patients continuing in an LTE study. Outcomes included low disease activity (LDA)/remission rates defined by Clinical Disease Activity Index (CDAI); Disease Activity Score in 28 joints (DAS28-4), erythrocyte sedimentation rate; DAS28-4, C-reactive protein (DAS28-4[CRP]); and rates of/time to discontinuation due to lack of efficacy/adverse events. RWD were identified by non-systematic literature searches of PubMed, Embase, and American College of Rheumatology/European Alliance of Associations for Rheumatology congress abstracts (2012-2022).

Results: RCT/LTE analyses included 1000/498 patients receiving tofacitinib 5 mg BID monotherapy. Baseline disease activity was high; patients tended to receive concomitant glucocorticoids; most were biologic DMARD-naïve. CDAI LDA rates were 32.2-62.2% for Groups 1/2 (months 3-12) and 64.0-70.7% for Group 3 (months 12-72). In Groups 1, 2, and 3, 4.0%, 15.6%, and 27.7% of patients, respectively, discontinued tofacitinib monotherapy due to lack of efficacy/adverse events. From 11 RWD publications, 16.6-66.1% received tofacitinib monotherapy. Consistent with clinical data, tofacitinib monotherapy effectiveness (month 6 CDAI LDA, 30.2%; month 3 DAS28-4[CRP] remission, 53.4%) and persistence were observed in RWD, with retention comparable to tofacitinib combination therapy.

Conclusion: Tofacitinib monotherapy demonstrated clinically significant responses/persistence in RCT/LTE analyses, with effectiveness observed and persistence comparable to combination therapy in RWD.

Trial registration: NCT00814307, NCT02187055, NCT01039688, NCT00413699, NCT00661661 (ClinicalTrials.gov).

Purpose: The prognosis of rheumatoid arthritis (RA) with interstitial lung disease (ILD) is particularly poor. Although drugs that do not contribute to the progression of ILD should be used in RA treatment, none have been established. This study evaluated the safety of tocilizumab in terms of ILD activity.

Patients and methods: This study prospectively enrolled all 55 patients with RA complicated by ILD who were treated with tocilizumab at Dokkyo Medical University Saitama Medical Center from April 2014 to June 2022. The outcome measures were MMP-3 and KL-6 as biomarkers of RA and ILD activity, respectively, and the relationship between them was analyzed.

Results: Both MMP-3 and KL-6 were significantly improved at 6 months of treatment (P < 0.001 and P < 0.05, respectively), and a weak correlation between MMP-3 and KL-6 was observed (R² = 0.086, P = 0.087). The group with increased MMP-3 due to RA progression had significantly higher KL-6 at 6 months compared with the group with RA improvement (P < 0.05). Also, the group with ILD progression on computed tomography had significantly higher MMP-3 compared with the groups with improvement or no change of ILD (P < 0.05 and P < 0.01, respectively). The mortality rate was 0% at 6 months, 2.0% at 1 year, 16.7% at 2 years, and 32.4% at 3 years, and mortality from acute exacerbation of ILD due to respiratory infection increased over time.

Conclusion: RA activity and ILD activity were found to be related at 6 months of treatment. Tocilizumab does not seem to affect the mechanism of ILD progression, as most patients showed improvement in both MMP-3 and KL-6 with tocilizumab within 6 months, when this drug would be expected to affect the lungs directly. However, respiratory infection exacerbated ILD from 1 year after the start of treatment. As immunosuppressive drugs, including tocilizumab, have a risk of respiratory infection, it is important to identify early signs of infection.

Background: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) have become the core effector cells for the progression of rheumatoid arthritis due to their "tumor-like cell" characteristics, such as being able to break free from growth restrictions caused by contact inhibition, promoting angiogenesis, invading surrounding tissues, and leading to uncontrolled synovial growth. In recent years, cold air plasma (CAP) has been widely recognized for its clear anticancer effect. Inspired by this, this study investigated the inhibitory effect of CAP on the tumor-like biological behavior of RA-FLS through in vitro experiments.

Methods: Treatment of RA-FLS with CAP at different time doses (0s, 30s, 60s, 120s). 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay was used to determine the cell viability. Analysis of cell migration and invasion was performed by wound-healing assay, transwell assay and immunofluorescent staining for f-actin, respectively. Flow cytometry technique was used for analysis of cell cycle and determination of reactive oxygen species (ROS). Hoechst staining was used for analysis of cell apoptosis. Protein expression was analyzed by Western blot analysis.

Results: Molecular and cellular level mechanisms have revealed that CAP blocks RA-FLS in the G2/M phase by increasing intracellular reactive oxygen species (ROS), leading to increased apoptosis and significantly reduced migration and invasion ability of RA-FLS.

Conclusion: Overall, CAP has significant anti proliferative, migratory, and invasive effects on RA-FLS. This study reveals a new targeted treatment strategy for RA.

Rheumatoid arthritis (RA) is a systemic, chronic, immune-mediated inflammatory condition. Treatments options encompass conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) like tumor necrosis factor (TNF) inhibitors (TNFis) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) including Janus Kinase inhibitors (JAKinibs). Orally administered JAKinibs have demonstrated comparable or, in specific cases, superior efficacy compared to bDMARDs in inflammatory conditions. However, the escalating clinical utilization has been accompanied by the emergence of serious adverse effects, including major adverse cardiac events (MACE), malignancies and venous thrombotic episodes (VTE), leading to regulatory restrictions imposed by health authorities in both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Objective: The current study aimed to determine the pregnancy outcomes complications in patients with SLE and its association with clinical, laboratory variables, disease activity, and medication use in the Saudi population, as well as pregnancy effect on disease activity.

Methods: A multicenter study included pregnant female patients with Systemic Lupus Erythematosus (SLE) from three tertiary centers in Saudi Arabia. The demographics, clinical, and laboratory variables, SLE disease activity index (SLEDAI), medication before, during, and after pregnancy, planned pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted.

Results: A total of 66 pregnant patients with SLE and 93 healthy age-matched pregnant controls were included in the study. A total of 77.3% had SLEDAI-2K ≤ 4 before conception, and 84.85% of pregnancies were planned. Age of conception, cesarean section, miscarriage, and low birth weight were statistically significant (p <0.05) higher in SLE patients than in healthy controls. Among all clinical and laboratory variables, SLEDAI-2K > 4 and active lupus nephritis during pregnancy were statistically associated with adverse outcomes (p <0.05), history of lupus nephritis was not associated with statistically adverse pregnancy outcomes. Higher SLEDAI-2K > 4 was an independent risk at least 4.87 times higher association with adverse pregnancy outcomes. (p <0.05).

Conclusion: SLE is intricately connected with unfavorable pregnancy outcomes. The preconception of high disease activity stands as a pivotal risk factor for adverse outcomes. Despite the disease remission and meticulous planning, SLE patients frequently grapple with disease exacerbations during pregnancy, culminating in unexpected and unfavorable pregnancy-related outcomes. This underscores the intricate and multifaceted nature of managing SLE during gestation.

Introduction: Spondyloarthritis (SpA) most commonly presents at childbearing age; thus, pregnancy is of concern. However, data on pregnancy outcomes in these patients are limited.

Purpose: This study aimed to retrospectively describe pregnancy outcomes in patients with SpA from the Middle East.

Patients and methods: We reviewed the electronic health records of all pregnant women attending a specialized pregnancy and rheumatic disease clinic between 2016 and 2022. All pregnant patients diagnosed with axial spondyloarthritis (axSpA) and peripheral SpA were included. Data on adverse maternal and fetal outcomes were collected.

Results: Fifty-seven eligible pregnancies were identified from hospital records: 10 pregnancies ended in early miscarriage. Forty-seven pregnancies resulted in live singleton births, 25 in patients with peripheral SpA and 22 with axSpA. Human leukocyte antigen B27 was positive in 7 (15%) patients and only in women with axSpA. Twenty-nine (64%) patients received treatment throughout pregnancy. Consistent biologic disease-modifying antirheumatic drug (bDMARD) use was high, in eight (32%) patients with peripheral SpA and in nine (41%) with axSpA. A conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) was used as treatment in 11 (50%) patients with peripheral SpA and two (8%) with axSpA. Twenty-two (53%) neonates were delivered by cesarean section, 19 (40%) by normal vaginal delivery and three (6%) by assisted delivery. Additionally, 44 (94%) deliveries were at term, and 42 (91%) neonates had a normal birth weight. Exploration of a subgroup showed no difference in reported outcomes between patients treated with bDMARD and those treated with csDMARD.

Conclusion: This descriptive study reports a high rate of favorable pregnancy outcomes in patients with SpA. There was no evidence to suggest a difference in pregnancy outcomes between women with axSpA and those with peripheral SpA. This study was one of the first reports from the Middle East. Further studies with larger sample size are warranted.

Purpose: To determine the value of lung ultrasound (LUS) compared to high-resolution computed tomography (HRCT) in the early diagnosis of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).

Patients and methods: An observational prospective study was performed. Were included patients with respiratory symptoms or/and, patients with crackles in auscultation during medical consultation. All patients underwent to chest X-rays, LUS, HRCT,and respiratory function tests.

Results: A total of 192 patients with RA were included. Mean disease duration was 16.8 ± 11.1 years. 72% were positive for rheumatoid factor or anti-citrullinated antibodies. Of the total number of subjects, 54.7% had respiratory symptoms. The other patients did not have respiratory symptoms, but they did have had crackles on pulmonary auscultation. B lines > 11.5 on the ROC curve predicted ILD (AUC 0.63; CI 95%: 0.55-0.71; p < 0.003). A DLCO value of <7.13 significantly predicted the presence of ILD (AUC 0.61; 95% CI: 0.52-0.70; p < 0.028).

Conclusion: The findings of this study suggest that LUS is a valuable tool for the early diagnosis of ILD in patients with RA, and together with DLCO, can adequately predict the presence of ILD in this population. LUS also helps to determine which patients with respiratory symptoms and signs suggestive for ILD are undergo to HRCT.

Background: The prevalence of gout has increased in the Western societies due to ageing and increasing BMI. Recently, lifestyle and dietary factors have been linked in epidemiological studies with an alteration of the risk of gout; however, there remains a lack of data on patient knowledge of these factors. The purpose of this survey-based study was to determine the knowledge of gout and its treatment both in the community and specialist care settings.

Methods: Participants were recruited from a hospital rheumatology outpatient department, consumer organization and a random sample of participants from a population-based cohort who had self-reported gout in South Australia. Participants completed a survey regarding basic demographics, the Single Item Literacy Screener, use of medication and diet for treatment of their gout and knowledge of gout.

Results: Seventy-four people were recruited (87% male) with a mean age of 66 years (range 35-88). The mean duration of gout was 16.6 years (range 0-60). On screening with SILS, 19.0% were identified as having limited reading ability. Most gout was managed by the family practitioner (81.1%) and/or rheumatologist (18.9%). In regard to current gout medications, 52.7% were taking allopurinol, 17.6% colchicine, 9.5% non-steroidal anti-inflammatory drugs, 6.8% prednisolone and 5.4% herbal preparations. For further information regarding gout, participants would most commonly approach their general practitioner (85.1%). Most participants correctly identified certain triggers to gout attacks and almost half of participants (41.9%) reported that they had altered their diet due to gout. Conversely, participants often incorrectly identified common risk or protective factors for gout.

Conclusion: Gout remains a common, yet undertreated, chronic condition. Our study highlights a lack of knowledge amongst patients of risk and protective factors in relation to gout. The increasing prevalence of gout within the population indicates a need to improve education and understanding among those with the condition.

Background: This pilot study measures pain perception, somatosensory amplification and its relationship to health anxiety in patients with fibromyalgia (FM) and patients with FM and obstructive sleep apnea (OSA); this study also examines the effects of OSA on pain perception in patients with FM.

Methods: In this pilot study, patients diagnosed with FM or FM and OSA, completed three self-reported questionnaires: Short-Form McGill Pain Questionnaire (SF-MPQ), Somatosensory Amplification Scale (SSAS), and Illness Behavior Questionnaire (IBQ). Sleep study results were analyzed. Scores were summarized using medians and interquartile ranges and are compared using Wilcoxon rank sum tests.

Results: Overall FM (n = 25), female n=23 male n=3 mean age, 57.48 years. OSA n=17 (68%) and 8 (32%) were not. The SF-MPQ Sensory sub-scale scores and the SF-MPQ overall scores differed significantly between patients with and without OSA. The SF-MPQ Sensory sub-scale scores were significantly lower for patients with OSA (p=0.03), as were SF-MPQ overall scores (p=0.04). SSAS overall scores and IBQ overall scores did not differ significantly by OSA diagnosis. Correlations of the different dimensions of IBQ with SSAS and mean number of diagnoses in FM and FM+OSA, mean number of diagnoses in problem list of SSAS ≤30 was 29.5, mean number of diagnoses in SSAS ≥30 was 34.9.

Discussion: Developing a better understanding of the effects of OSA on pain perception in patients with FM is needed for improved health status. More research is needed to see if higher pain perception and SSAS score lead to increased health care utilization and to evaluate the relationship between untreated disordered sleeping and pain perception in patients with FM.

Conclusion: Our findings highlight the need for more research to evaluate the relationship between treated and untreated disordered sleeping, pain perception, somatization and illness behavior in the health status of individuals with FM.

Takayasu arteritis (TA) is a large vessel arteritis that predominantly affects the aorta and its major branches. Its association with tuberculosis (TB) has been described in the literature. This association poses a diagnostic and therapeutic challenge, especially in TB-endemic areas. We report a case of a young Ethiopian female patient who was diagnosed with TA associated with TB. We discuss the diagnostic and therapeutic challenges of this association.