ACR open rheumatology最新文献

Objective: Despite advances in rheumatoid arthritis (RA) treatment, a considerable proportion of patients exhibit refractory disease, prompting the need for a comprehensive understanding of refractory RA. We aimed to analyze the burden and patient experiences associated with initiation of a third biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (BT3-RA) in a large observational cohort.

Methods: Data were obtained from participants with RA in the FORWARD Databank from 1999 to 2019. Participants, stratified into BT3-RA and a comparator BT1-RA (first initiation of a b/tsDMARD) cohorts, were matched based on key demographic and disease-specific parameters. Demographics, patient-reported outcomes (PROs), comorbidities, and health care interactions were assessed at initiation of first advanced therapy and at the time of meeting BT3-RA criteria.

Results: After matching, 1,384 participants were included in the study (692 each for BT3-RA and BT1-RA). The BT3-RA cohort had worse PROs, greater comorbidity burden, and lower health satisfaction than BT1-RA controls. Those with BT3-RA had significantly higher odds of having a greater number of rheumatology visits in the previous six months than controls (>4 visits, 0-2 visit reference, odd ratio [OR] 3.8 [95% confidence interval (CI) 2.7-5.4], P < 0.001; 3-4 visits, 0-2 visit reference, OR 1.9 [95% CI 1.5-2.5]; P < 0.001). Those with BT3-RA also had higher odds of concomitant glucocorticoid use (OR 1.5 [95% CI 1.2-2.0], P < 0.001) and gastrointestinal disorders (OR 1.5 [95% CI 1.1-1.9], P < 0.01).

Conclusion: Exposure to three advanced RA therapies was associated with significant disease burden and unmet health care needs. These findings underscore the importance of well-defined refractory criteria and the need for further investigation into this RA phenotype to identify targeted treatment strategies and ultimately improve outcomes.

Objective: The synovial tissue pathotype may determine the treatment response in rheumatoid arthritis (RA); however, biopsies are not widely available. Synovial fluid is a promising tissue surrogate. Our purpose was to compare RA synovial fluid cell counts with histopathology and use synovial fluid to predict tissue inflammation.

Methods: Synovial fluid and tissue were collected during knee arthroplasty. Patients were stratified based on their medication treatment history. Synovial lymphocytic inflammation (SLI) was graded from low to high. Synovial fluid white blood cell (WBC) count and differentials were performed in the clinical laboratory. Descriptive statistics, correlations, receiver operating characteristic curve analysis, and multivariable regression were performed to determine the associations with tissue SLI.

Results: Sixty-four patients with RA had paired synovial tissue and synovial fluid data available. The mean Clinical Disease Activity Index (CDAI) score was 17.9. High tissue SLI was observed in 29 patients, and low SLI was observed in 35 patients, with roughly equal distribution among treatment groups. The mean synovial fluid WBC count was 5,661 cells/μL and was not correlated with CDAI but correlated positively with SLI and percentage polymorphonuclear cells (PMN%). Synovial fluid WBC count ≥1,400 cells/μL was sensitive (0.86) and specific (0.91) for high SLI (area under the curve 0.91). In a multivariable regression, PMN% was associated with high SLI (odds ratio [OR] 1.46 [95% confidence interval (CI) 1.14-1.85]). Synovial fluid monocyte percentage was negatively associated with high SLI (OR 0.44 [95% CI 0.27-0.73]).

Conclusion: Synovial fluid WBC count is sensitive and specific for differentiating high and low lymphocytic synovial inflammation. Further analysis of the synovial fluid as it relates to the adjacent tissue in different cohorts is needed.

Objective: To evaluate the clinical characteristics and serum cytokine profiles of patients with anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease (MDA5+ DM-ILD) treated with JAK inhibitors and to compare survivors and nonsurvivors.

Methods: Six patients diagnosed with MDA5+ DM-ILD at Nagasaki University Hospital (from 2018 to 2023) were analyzed. All patients received high-dose glucocorticoids, intravenous cyclophosphamide, and plasma exchange. Five patients received calcineurin inhibitors. JAK inhibitors (tofacitinib, n = 3; baricitinib, n = 3) were added to the treatment regimen. Clinical data, including serum ferritin levels, hypoxemia status, and lymphocyte counts, were recorded at initial presentation and during JAK inhibitor treatment. Serum cytokine levels were analyzed using multiplex assays.

Results: The mean patient age was 66.6 years, and four patients were women. Three patients died within six months of starting JAK inhibitor therapy. Nonsurvivors had higher initial ferritin levels than survivors (mean 3,413 vs 809 ng/mL). Hypoxemia was present in five patients at JAK inhibitor initiation, and four patients had low lymphocyte counts. Serum cytokine analysis revealed elevated levels of granulocyte colony-stimulating factor, interferon-α, interleukin-4, interleukin-13, and CXCL8 in nonsurvivors compared with survivors.

Conclusions: Serum cytokine profiles may serve as prognostic markers in patients with MDA5+ DM-ILD treated with JAK inhibitors. The persistent elevation of multiple cytokines in nonsurvivors may reflect inadequate suppression of the cytokine storm despite treatment. Further research is needed to determine the optimal selection and timing of JAK inhibitor therapy.

Objective: Prompt referral to a rheumatologist is essential for the prevention of joint damage in people with inflammatory arthritis (IA). We investigated whether rheumatology referrals can improve triage if additional information from two self-assessment tools, namely the tender joint count (TJC) and the Early Inflammatory Arthritis Detection Tool (EIADT), was included with the referral letter.

Methods: Newly referred patients with no history of IA were recruited from two rheumatology practices. All patients were randomly allocated within a 2 × 2 factorial design to one of the following four groups: (1) no self-assessment, (2) TJC + EIADT, (3) TJC, and (4) EIADT. Participants were blinded to group allocation. Primary outcome was urgency rating, which was either 0 to 4 weeks, 4 to 6 weeks, 6 to 12 weeks, or nonurgent (>12 weeks). For each patient, an urgency rating was assigned to each of the following: (1) referral letter, (2) referral letter plus self-assessment, and (3) clinical assessment.

Results: Two hundred two patients were recruited and allocated across the four groups. Compared to referral letter alone, adding self-assessment to the referral letter significantly increased the number of participants marked nonurgent in the EIADT group (P < 0.05, McNemar-Bowker test), but not in any of the other groups. Also, in the EIADT group, clinical assessment did not significantly increase the number of nonurgent ratings compared to referral letter plus self-assessment (P ≥ 0.05, McNemar-Bowker test).

Conclusion: Including the EIADT with the referral letter may improve triage for new referrals.

We report a 49-year-old male patient with a normal serum uric acid and recent diagnosis of acute promyelocytic leukemia (APL) who developed a severe polyarticular gout flare during treatment with arsenic trioxide (ATO). Unlike conventional chemotherapies, ATO acts through the generation of reactive oxygen species (ROS), leading to APL cell apoptosis. The gout flare in our patient was initially treated with high-dose intravenous glucocorticoids with no clinical response and was subsequently treated with interleukin-1β receptor blockade, which resulted in complete clinical resolution of his gout. Our case offers insights into inflammatory pathways in gout, including the evolving role of ROS in autoinflammation.

Objective: To assess differences in perception between patients and physicians regarding the determinants of the burden of systemic lupus erythematosus (SLE) in France.

Methods: An online survey was conducted by IPSOS, a market research company, among adult patients with SLE and physicians (internists, rheumatologists, nephrologists, and dermatologists) involved in SLE care. The questionnaires were designed by a committee of lupus experts and patient research partners to cover key areas: symptoms experienced by patients with SLE, social and economic impact of the disease, and needs and expectations for the improvement of care pathways. Most questions were formulated to assess comparatively how they were perceived by patients and physicians.

Results: Responses from 107 patients and 101 physicians were analyzed. Regarding experienced symptoms, a patient-physician discordance was observed on the number of reported symptoms (P < 0.001) and in terms of prioritization, especially with the impact of extreme fatigue (76% vs 51%; P < 0.001) and anxiety and depression (45% vs 13%; P < 0.001), even outside flare-up periods. Physicians rarely reported that SLE significantly impacts all areas of their patients' lives, including physical, psychological, social, professional, sexual, and emotional aspects, whereas most patients expressed a lack of medical advice on areas such as sexual and emotional health, family life, professional life, and anxiety. Most patients also declared a perceived lack of information about treatment adverse effects, available therapeutic options, and potential causes of SLE.

Conclusion: This survey highlights the significant patient-physician discordances about the burden of SLE in France and supports the need for specific interventions to improve patient information and holistic care.

Objective: Interstitial lung disease (ILD) is common in idiopathic inflammatory myositis (IIM), particularly in antisynthetase syndrome (ASyS), antimelanoma differentiation-associated protein 5 (anti-MDA5) syndrome, and scleromyositis. ILD can progress despite resolution of extrapulmonary symptoms, termed postmyopathic progressive pulmonary fibrosis (PmPPF). We outlined ILD trajectories in these subgroups of IIM, focusing on PmPPF.

Methods: A retrospective review of patients with IIM (ASyS, anti-MDA5+ dermatomyositis [DM], scleromyositis) from a British Columbia cohort (2019-2024) assessed demographics, auto-antibodies, treatments, and ILD progression.

Results: Among 111 patients with ASyS, anti-MDA5+ DM, and scleromyositis (median age 51 years, follow-up 35.5 months), ILD prevalence was highest in ASyS (87.5%), followed by anti-MDA5+ DM (84.6%), and scleromyositis (65.5%). PmPPF occurred in 13.5% of the cohort, predominantly in anti-MDA5+ DM (23.1%) and ASyS (16.1%) but not in scleromyositis. Patients with PmPPF had higher rates of active disease (46.7% vs 9.3%), rapidly progressive ILD (33.3% vs 5.3%), and lung transplantation (20% vs 1.3%). Anti-MDA5+ DM exhibited the highest remission rate (88.5%) but also the highest transplant requirement (11.5%). Organizing pneumonia (OP)/nonspecific interstitial pneumonia (NSIP) overlap on high-resolution computed tomography was more common in PmPPF (33.3% vs 9.3%). PmPPF showed a nonsignificant trend toward higher mortality compared to non-PmPPF (20% vs 4%). Rituximab use was greater in PmPPF (73.3% vs 37.3%).

Conclusion: This study highlights distinct ILD patterns across three idiopathic inflammatory myopathy subtypes, with PmPPF occurring more frequently in ASyS and anti-MDA5+ DM but not in scleromyositis. The persistence of ILD progression independent of extrapulmonary disease activity underscores the importance of ongoing pulmonary monitoring and multidisciplinary management.