Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the predominant types of large-vessel vasculitis, sharing IL-6-mediated immunopathology but differing in age profile and clinical phenotype. Glucocorticoids (GC) remain standard for induction therapy, although relapse rates and treatment-associated toxicity on GC monotherapy are high. Therefore, current guidelines support early tapering and the use of GC-sparing agents in relapsing or high-risk patients. Tocilizumab is now established as standard therapy in GCA, while methotrexate remains an alternative option. Recently, the janus kinase (JAK) inhibitor upadacitinib has gained regulatory approval for GCA, supported by results of a phase 3 trial. In TAK, conventional immunosuppressants are used in new-onset disease, while TNF-alpha or IL-6-blockade can be considered in relapsing or refractory disease. Optimal duration of treatment is not yet well defined.

Post-stroke inflammation contributes to poor outcomes in both clinical and experimental studies. Interleukin-6 (IL-6) is a key inflammatory mediator in ischemic stroke, and higher circulating IL-6 levels are associated with greater stroke severity and worse clinical outcomes. Targeting IL-6 signaling therefore represents a potential therapeutic strategy. We tested whether inhibition of IL-6 signaling with the IL-6 receptor (IL-6R) blocking antibody tocilizumab (TCZ) improves recovery after experimental stroke. Aged mice (18-20 months) underwent 60 minutes of middle cerebral artery occlusion. TCZ (20 mg/kg) was administered 5 hours after ischemia onset, and behavioral outcomes were assessed weekly for 5 weeks. Delayed TCZ treatment improved long-term functional recovery in aged male mice but not in aged females. To explore this difference, we measured circulating soluble IL-6R (sIL-6R) levels in mice and patients with ischemic stroke. Females exhibited significantly higher post-stroke sIL-6R levels. Increasing the TCZ dose to 100 mg/kg restored efficacy in aged female mice and improved long-term outcomes. These findings support a role for IL-6R pathway modulation in improving recovery after experimental stroke and suggest that therapeutic response may differ by sex and target availability, potentially related to differences in circulating sIL-6R after ischemic injury.

We report a 72-year-old patient with intermittent fever for 7 months, accompanied by leukocytosis, tachycardia, myalgias and arthralgias. Prior evaluations-including imaging, cultures, bone marrow biopsy, serologies, and autoimmune panels-were unrevealing. The patient's persistent fever was previously diagnosed as fever of unknown origin (FUO), which is defined by a core temperature exceeding 38.0 °C for more than 3 weeks with no defined causes during ≥ 3 inpatient days or ≥ 3 outpatient visits. The patient's fever initially improved with steroids. During the hospital course, empiric antibiotics were started and discontinued following negative blood cultures, and prednisone was reinitiated at discharge. There was high suspicion for atypical adult-onset Still's disease (AOSD), and the patient was treated in the outpatient setting with steroids and tocilizumab. This case highlights the importance of systematic evaluation, multidisciplinary collaboration, and careful selection of pharmacological therapy and invasive procedures in the workup of FUO, especially in an elderly patient. The case also illustrates the challenges in diagnosing AOSD due to the highly variable clinical presentation and low prevalence, and further outlines current treatment recommendations for AOSD, which include corticosteroid therapy in combination with an interleukin (IL)-6 inhibitor.

Chimeric Antigen Receptor T-cell (CAR-T) therapy, where genetically engineered patient T cells target tumor antigens, has transformed care for hematologic malignancies but requires careful tracking of adverse events (AEs) often documented only in unstructured EHR notes. We evaluated a Large Language Model (LLM)-based approach in UCSF's secure environment to extract AEs, dates, grades, and interventions within 30 days post-infusion for six commercial CAR-T products (2012-2023), benchmarking against two evaluators. Using GPT-4-0314 in a zero-shot setting with four prompts (prespecified AEs, non-prespecified AEs, CRS, ICANS), we compared outputs against dual annotations on a random sample of 50 notes using accuracy, precision, recall, F1, and Cohen's kappa. From 4,762 progress notes for 293 patients (median age 65.6), CRS occurred in 80.2% (median onset 4 days); neutropenia 70.0% (16 days); neutropenic fever 64.8% (4 days); ICANS in 34.8%. Interventions included tocilizumab and corticosteroids. Grades were frequently undocumented (CRS 62.3%, ICANS 56.1%); documented cases were mainly CRS grade 1 (59.4%) and ICANS grade 2 (28.0%). Performance was high on CRS and ICANS grading (accuracy of 0.97 and 0.91, respectively). Moderate performances were assessed for prespecified AE extraction (accuracies 0.62-0.76), and non-prespecified AEs (accuracies 0.76-0.84). Inter-rater reliability was strong to near-perfect for CRS/ICANS presence and grade (kappa 0.86-0.96), moderate for dates and interventions, and weaker for broader AE attributes. LLM-derived insights can augment AE monitoring and real-world evidence generation by unlocking unstructured clinical detail and characteristic timelines after CAR T. However, performance varied for broader AE attributes, warranting cautious use. Performance was highest for detecting the presence and grade of CRS and ICANS, with strong to near-perfect inter-rater reliability. While cautious use of LLMs for broad AE extraction is warranted due to the variable performance observed in this study, these results support integrating high-performing CRS/ICANS extraction into EHR workflows.

Cytokine release syndrome (CRS) is a rare but serious complication of rabbit anti-thymocyte globulin, a common induction medication for solid organ transplant recipients. We present a case of grade 4 cytokine release syndrome in a renal transplant patient in whom tocilizumab successfully salvaged the graft function and stabilized the patient. A 22-year-old woman with end-stage renal disease on hemodialysis and a complex history including systemic lupus erythematosus nephritis underwent a deceased donor kidney transplant with thymoglobulin induction. Hours postoperatively, she developed hemodynamic collapse with escalating vasopressor requirements. Elevated IL-6 supported a diagnosis of CRS, and transthoracic echocardiogram suggested acute cardiogenic shock, requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Treatment with tocilizumab, an IL-6 receptor-blocking monoclonal antibody, resulted in a 76% decrease in IL-6 and subsequent gradual recovery. She was decannulated, weaned off pressors, and extubated over the next week. She was discharged 24 days postoperatively with preserved allograft function and adequate urine output that remained stable after 6 months. This report describes a rare case of severe CRS and acute cardiogenic shock after thymoglobulin induction and highlights the complexities of diagnosing shock of unknown etiology. Tocilizumab shows a promising role in treating post-transplant cytokine crisis, though reports of its use in thymoglobulin-induced CRS in perioperative kidney transplant recipients remain limited. Finally, we show how a multimodal treatment approach of tocilizumab, VA-ECMO, and best care practices was able to preserve the function of the allograft transplant.

The interleukin-6 (IL-6) inhibitors tocilizumab and sarilumab have been repurposed for COVID-19 treatment. However, discrepancies exist across global and national COVID-19 guidelines, with limited data on the comparative effectiveness between these therapeutics especially during the delta/omicron periods. With the approval of NHS England and Public Health Scotland, we compared their effectiveness among adults hospitalised with COVID-19 using electronic health records data through the OpenSAFELY-TPP (England) and EAVE II (Scotland) platforms. Following the target trial emulation framework, 10,487 patients treated between July 2021 and February 2022, when both drugs were frequently prescribed, were included. In England, 1150 (20.1%) of 5710 participants receiving tocilizumab died by day 28 compared with 820 (20.4%) of 4025 participants receiving sarilumab (adjusted hazard ratio [aHR] 1.07, 95% CI 0.96-1.19). In Scotland, 114 (29.4%) of 388 participants receiving tocilizumab died by day 28 compared with 97 (27.0%) of 359 participants receiving sarilumab (aHR 0.92, 95% CI 0.68-1.23). There was no evidence of a difference in time to hospital discharge between the groups, and no credible effect modification by variant of concern, vaccination status, age, sex, ethnicity, body mass index, or comorbidities. Our findings provide supportive evidence for both drugs as alternative therapeutic options in COVID-19 in-patient management.