悪性関節リウマチ

BACKGROUND: The prevalence of hypertrophic pachymeningitis (HP) remains poorly defined worldwide. In Japan, the estimated prevalence is 0.949 cases per 100,000 inhabitants, with most cases related to ANCA-associated vasculitis or IgG4-related disease. In contrast, epidemiological data from other regions, including Latin America, are scarce. METHODS: This study was conducted at a tertiary referral center in the city of São Paulo, Brazil. The prevalence of HP was estimated by comparison with the known prevalence of multiple sclerosis (MS), based on the number of patients with each condition followed at our institution. The etiological distribution of HP was also analyzed. In addition, HP prevalence was compared with that of tuberculous meningoencephalitis, a compulsory notifiable disease and a well-established cause of chronic meningitis in Brazil, using data from the national surveillance system (SINAN). RESULTS: We identified 55 patients with HP: 36 (65%) idiopathic, 10 (18%) IgG4-related disease, 4 (7%) ANCA-associated pachymeningitis, 4 (7%) probable or definite neurosarcoidosis, and 1 (2%) secondary to rheumatoid arthritis. Among 968 registered MS patients and assuming an MS prevalence of 15 per 100,000 inhabitants in São Paulo, the estimated HP prevalence was 0.85 per 100,000 inhabitants. This estimate was comparable to the prevalence of tuberculous meningoencephalitis in the same region. CONCLUSION: The estimated prevalence of HP in São Paulo (0.85 per 100,000) is consistent with reports from other regions and is comparable to that of tuberculous meningeal disease, although with a distinct etiological profile. IgG4-related disease was the most frequent systemic association, differing from previous reports. ANCA-associated HP appears to be less frequent than in other geographic regions, possibly reflecting differences in disease phenotype. Key Points • The estimated prevalence of HP in São Paulo was 0.85 per 100,000 inhabitants. • IgG4-related disease was the most common systemic disease identified among patients with HP. • ANCA-associated HP was less common than reported in Asian and European cohorts. • The prevalence of HP was comparable to that of tuberculous meningoencephalitis in São Paulo.

BACKGROUND: Rheumatologic diseases significantly impact health-related quality of life (HRQoL), affecting physical, mental, and social well-being and pose unique challenges due to their wide range of symptoms. Patient-reported outcomes (PROs) provide valuable insights into how these diseases influence different dimensions of HRQoL, supporting personalized healthcare approaches. METHODOLOGY: In this cross-sectional study, we examined HRQoL in 213 patients with rheumatologic diseases, including, among others, rheumatoid arthritis, localized pain disorders, connective tissue diseases, and rarer conditions such as vasculitis, using the EQ5D-5L and the Patient-Reported Outcomes Measurement Information System (PROMIS®) as well as Pain and HRQoL specific PROs. We provided PROMIS health domain scores of key health aspects such as physical function, fatigue, pain interference, and social participation. Additionally, we compared HRQoL and PROMIS domain scores with a German general population reference sample and conducted exploratory comparisons across the three most frequent principal diagnosis groups: systemic sclerosis, rheumatoid arthritis, and vasculitis. Moreover, we investigated which patient-reported health domains were most strongly associated with HRQoL in these diseases. Penalized regression models with elastic net regularization were used to identify stable predictors of HRQoL, followed by a pooled linear regression model for interpretation. RESULTS: Individuals with rheumatic diseases had significantly lower HRQoL than the general population (EQ-5D-5L VAS mean: 55.4 versus 73.2). PROMIS T-scores indicated markedly reduced Physical Function (M = 36.5, SD = 9.6) and elevated pain interference (M = 61.7, SD = 9.2). Penalized regression analyses identified Physical Function, Fatigue, Ability to Participate in Social Roles and Activities as stable predictors of EQ-5D-5L VAS. Higher Physical Function and Social Participation were associated with higher HRQoL, whereas higher Fatigue was associated with lower HRQoL. CONCLUSIONS: These results highlight the importance of PROs in understanding the patient experience in rheumatologic disease and identifying individual needs. Routine assessment of HRQoL domains may help recognize unmet needs and support individualized care in rheumatology.

INTRODUCTION: The regimen of rituximab we not determined based on evidence from pharmacokinetics. However, rituximab exhibited significant pharmacokinetic variability among different clinical populations, which might be a key factor influencing individual exposure and response to this monoclonal antibody. This systematic review aimed to analyze the traditional and population pharmacokinetics of rituximab and to investigate covariates influencing its pharmacokinetics. METHODS: A systematic search was conducted in three English databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and two Chinese database (China National Knowledge Infrastructure and Wanfang Data). Traditional and population pharmacokinetics of rituximab conducted in humans were included. Study designs, population characteristics, pharmacokinetic parameters, and covariates were extracted. The ClinPK's checklist was used to assess the reporting quality of the included studies. The PROSPERO registered ID was CRD420251085784. RESULTS: The systematic research yield 25 traditional pharmacokinetics studies and 26 population pharmacokinetics studies. The included studies mainly investigated the pharmacokinetics of rituximab in patients with non-Hodgkin's lymphoma, rheumatoid arthritis, kidney disease and anti-neutrophil cytoplasmic antibody-associated vasculitis. Significant variability in pharmacokinetic parameters existed among different clinical populations as well as among different subjects encountering similar clinical conditions. Most (23, 88.5%) population pharmacokinetics studies used a two-compartment model to describe rituximab pharmacokinetics. However, the elimination kinetics were inconsistent including the first-order elimination, time-varying elimination and target-mediated drug disposition. Body size descriptors such as body surface area, body mass index and body weight were the most frequently observed significant covariates, which appeared in 17 studies. Other significant covariates included gender, basal CD19+/20+ count, tumor stage, baseline total metabolic tumor volume, anti-drug antibodies, disease progression, urinary protein to creatinine ratios and the number of rituximab treatment courses. In addition, the pharmacokinetic parameters of rituximab biosimilars were proved to be non-inferior to that of the originators. Compared with intravenous administration, subcutaneous administration with a specific dose of 1600 mg or 1400 mg could achieve non-inferior Ctrough in chronic lymphocytic leukemia and diffuse large B-cell lymphoma respectively. CONCLUSION: This systematic review presented a comprehensive overview of rituximab's pharmacokinetics across various clinical populations. It highlighted the complexity and variability of rituximab's pharmacokinetics. Future research should place emphasis on the model informed precision dosing of rituximab based on pharmacokinetics and various influencing factors in clinical practice.

OBJECTIVES: The increasing use of tumor necrosis factor (TNF) inhibitors poses new challenges in terms of drug iatrogenicity and diagnosis. In this study, we focus on the description of the TNF-inhibitors-induced vasculitis. METHODS: We conducted a retrospective descriptive study using the French national pharmacovigilance database to study cases of vasculitis attributable to TNF-inhibitor treatment. RESULTS: A total of 164 cases were analyzed, patients' mean age was 49.1 years, and 61.4% were women. The indications for TNF-inhibitor therapy were Crohn's disease (27%), rheumatoid arthritis (27%) and ankylosing spondylitis (21%). The median time to onset of vasculitis was 390 days [120-1095]. Clinical manifestations included cutaneous manifestations (88%), mainly purpura, rheumatic manifestations (27%), general symptoms (15%), renal manifestations (14%) and gastrointestinal and neurological manifestations (8% each). Skin biopsy was the most important diagnostic test, with 67.7% of cases showing vasculitis. Our study found mainly nonspecific vasculitis (54.9%), IgA vasculitis (28%) and ANCA vasculitis (7.9%). A possible association was observed between IgA vasculitis and TNF-inhibitors treatment for Crohn's disease, compared with other indications. CONCLUSION: Our study, based on national pharmacovigilance data, provides a better characterization of TNF-inhibitor-induced vasculitis. Resolution of vasculitis upon TNF inhibitor discontinuation, followed by recurrence upon reintroduction, confirms the drug's causative role and suggests that treatment should be stopped if possible. Clinicians should exercise heightened vigilance for symptom onset within the first 500 days of therapy. The atypical features of certain vasculitis, particularly from an epidemiological perspective given the unusual age at presentation, should prompt consideration of an iatrogenic etiology, including potential anti-TNF involvement.