Rheumatology最新文献

Objective: To examine cancer risk associated with Janus kinase inhibitors (JAKis) and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA).

Methods: Case-control study of patients with RA age 65 years or older in the United States Surveillance, Epidemiology, and End Results (SEER)-Medicare database during 2014-2019. Cases were individuals with a first cancer diagnosed in SEER registries (N = 12 463). Cancer-free controls (N = 38 345) were Medicare beneficiaries residing in SEER areas. Exposure to JAKis, tumor necrosis factor inhibitors (TNFis), and other bDMARDs was ascertained using prescription claims. Logistic regression was used to estimate adjusted odds ratios (ORs).

Results: 1.9% of cases and 2.0% of controls were prescribed a JAKi. Among patients prescribed a JAKi, the median duration of documented exposure was 1.8 years. Overall cancer risk was not associated with exposure to JAKis (adjusted OR 1.04, 95% confidence interval [95%CI] 0.87-1.26), TNFis (0.98, 0.92-1.05), or other bDMARDs (0.98, 0.90-1.07). However, JAKi exposure was associated with significantly increased risk of lung cancer (OR 1.40, 95%CI 1.06-1.87), especially in males (2.12, 1.14-3.94) and with >2 years of JAKi exposure (1.52, 1.01-2.28). Among females, JAKi exposure was associated with lower risk of breast cancer (OR 0.62, 95%CI 0.39-0.97).

Conclusions: Among older adults with rheumatoid arthritis, JAKi exposure over a median of 1.8 years was not associated with an overall increase in cancer risk. However, lung cancer risk was elevated, supporting clinical caution in prescribing this medication class to smokers. Further research is needed to understand the role of the JAK/STAT pathway in cancer.

Objectives: Janus kinase inhibition (JAKi) has been proposed as a treatment for idiopathic inflammatory myopathies to target increased interferon signalling. Predominantly retrospective reports have demonstrated effectiveness of JAKi in refractory juvenile dermatomyositis (JDM). However, JAKi remains an off-label treatment for JDM and there may be variation in use worldwide. An international survey was conducted to investigate approaches to JAKi for JDM.

Methods: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Therapeutics workgroup and core members of the Paediatric Rheumatology European Society (PReS) JDM working party devised an electronic survey to assess the use of JAKi in JDM. CARRA and PReS members were invited by email to complete the survey.

Results: There were 229 respondents (18%), with 50% from the US and 29% from Europe. 150 had used JAKi for over 450 patients with JDM; among them, 77% noted clinical improvement in most or all patients and 17% reported side effects. The highest ranked perceived barriers to JAKi use were lack of clinical data and inability to obtain insurance approval. The highest ranked clinical indications for starting JAKi were refractory skin disease, refractory muscle disease, inability to wean steroids, and intolerance to other steroid-sparing agents.

Conclusion: Pediatric rheumatologists use JAKi off-label treatment for refractory JDM. Most providers noted clinical improvement in their patients. Barriers to JAKi use include lack of clinical data and insurance coverage. Clinical trials are needed to provide better data on the efficacy and safety of JAKi.

Objectives: Obesity affects 53% of gout patients, while its effect on urate-lowering therapy (ULT) is unclear. This study aimed to compare the response to febuxostat among different body mass index (BMI) catalogs of male gout patients.

Methods: A prospective study recruited 633 men with gout, classified by BMI into normal-weight, overweight, and obese groups. Baseline age, disease duration, and serum urate (SU) levels were matched simultaneously. All participants received febuxostat for 12 weeks, increasing the dosage from 20 to 40 mg daily. We compared the efficacy of ULT and the incidence of gout flares in three groups. Cox regression analysis was used to identify risk factors for achieving target SU levels before and after matching. Restricted cubic spline (RCS) curves were used to illustrate the relationship between BMI and hazard ratio (HR) for SU achievement.

Results: The proportion of participants achieving SU < 6.0 mg/dl in the obese group was 38.9%, significantly lower than the overweight (54.2%) and normal-weight groups (63.8%) (p < 0.05), with no significant difference between the overweight and normal-weight groups at week 12. High BMI (HR = 0.92, 95% CI 0.89-0.96, p < 0.001) independently prevented achieving the SU target, with a similar effect after matching. Obese and overweight individuals had a higher cumulative incidence of gout flares compared with the normal-weight group (p < 0.05). The linear relationship between BMI and HR for achieving the SU target was suggested by RCS (nonlinear p > 0.05).

Conclusion: Obesity significantly reduces the efficacy of febuxostat-based ULT in male gout patients rather than being overweight.This study was registered in the China Clinical Trial Registry (#ChiCTR2300078804).

Objectives: Acute chikungunya virus infection often leads to chronic post-infection arthritis, but investigation and evaluation of treatment is hampered by the subjectivity of symptoms. This study was designed to evaluate ultrasound scores and serum inflammatory markers as objective measures for the severity of chronic post-chikungunya arthritis.

Methods: Patients with acute chikungunya virus infection were enrolled in a prospective study and followed up at 3, 6 and 12 months. Assessments included both a physical exam and standardised ultrasound examination of 40 joints. Symptom severity and patient reported outcomes were recorded, and serum inflammatory markers were measured. Global ultrasound synovitis and tenosynovitis scores were calculated and correlation of ultrasound and serum markers with clinical symptoms and outcomes was analysed.

Results: 60 patients (mean age 34 years, 67% female) were followed up. Widespread joint involvement was observed in the acute infection phase. This was followed by increasing involvement of small joints contributing to persistent symptoms in 57% of patients at 3 months and 30% at 12 months. Global ultrasound scores for synovitis at 3 months correlated with tender joint counts (r = 0.54, p< 0.0001), pain severity (r = 0.59, p< 0.0001), musculoskeletal stiffness (r = 0.42, p< 0.001) and RAPID3 scores (r = 0.59, p< 0.0001), confirmed at 6 and 12 months. Serum inflammatory markers were poorly associated with persistent symptoms during follow-up.

Conclusion: Global ultrasound scores for synovitis were found to be a relevant measure to support clinical observations in studies of chronic post-chikungunya joint disease.

Objective: To determine the prevalence and predictive factors of cerebrovascular accidents (CVA) in giant cell arteritis (GCA).

Methods: ARTESER is a large Spanish multicentre registry including patients with GCA from across the entire country diagnosed between June 2013 and March 2019 and sponsored by the Spanish Society of Rheumatology. The variables collected at diagnosis were demographics, clinical manifestations (including the occurrence and location of CVA), laboratory, histology and imaging findings. Patients with and without CVA were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of CVA.

Results: A total of 1540 patients with GCA were included for analysis (mean age 77.1 years, 70% females). CVA occurred in 61 (3.96%), of whom 38 (62.3%) involved the vertebrobasilar territory and 21 (34.4%) the carotid territory. The factors associated with CVA were the occurrence of transient ischaemic attack (TIA) (OR 8.63; 95% CI 2.877-25.86), large vessel (LV) involvement (OR 2.79; 95% CI 1.421- 5.465) and the presence of concomitant visual manifestations (OR 2.73; 95% CI 1.427-5.235). The risk of death during follow-up was significantly higher in patients with CVA (18% vs 8.8%; p= 0.014). Patients with CVA received significantly higher mean prednisone (mg) dose at diagnosis (433.9 vs 216; p< 0.001) and cumulative prednisone dose during follow-up (11 203.9 vs 8,194.1; p< 0.001).

Conclusion: The prevalence of CVA in patients with GCA is low, but increases the risk of mortality. The presence of TIA, LV involvement and visual manifestations are factors associated with increased risk of CVA.