Lisa Christ

ANCA-associated small vessel vasculitis (AAV) and giant cell arteritis (GCA) are two clinically distinct forms of vasculitides with a high risk of relapse. We aimed to evaluate and compare the role of immune cells in patients with both vasculitis subtypes with active disease. Whole blood was collected from 12 untreated newly diagnosed or relapsing patients with AAV, 10 untreated newly diagnosed patients with GCA, and 11 age- and sex-matched healthy controls (HC). Transcriptomes were analysed by RNA sequencing. Differentially expressed genes (DEG) were calculated across disease groups. Pathway enrichment analysis was conducted using Overrepresentation Analysis (ORA), and Gene Onthology and Gene Set Enrichment Analysis (GSEA). The platelet receptor component CD42a was assessed by flow cytometry. We identified 104 DEG in AAV compared to HC, and 504 DEG between GCA and HC in whole blood samples. Strikingly, only 19 genes were differentially expressed between AAV and GCA. ORA of DEG, distinguishing both vasculitis subtypes from HC, identified pathways exclusively involved in innate immunity. GSEA of both AAV and GCA versus HC pointed to a striking overlap in up-regulated pathways comprising seven out of ten top signalling pathways, including “IL6 JAK Stat3 signalling”, “TNF signalling” and “complement activation”. We detected increased levels of CD42a on platelets of patients with GCA, in line with an increased expression of platelet-associated genes in GCA compared to AAV. Our results suggest that the rather homogeneous transcriptome of circulating immune cells does not sufficiently explain the clinically distinct phenotypes of AAV and GCA.

Zusammenfassung: Die European Alliance of Associations for Rheumatology (EULAR) hat im Juli 2026 ihre Leitlinien für Polymyalgia rheumatica (PMR), Riesenzellarteriitis (RZA) und Takayasu-Arteriitis (TAK) erstmals in einem gemeinsamen Dokument zusammengefasst. Dahinter steht ein moderneres Verständnis der klinischen Zusammenhänge zwischen PMR und RZA sowie der Herausforderungen in der Behandlung von Grossgefässvaskulitiden. Zentral ist ein Paradigmenwandel hin zum möglichst sparsamen Einsatz von Glukokortikoiden (GC). Bei RZA-Verdacht und kraniellen Symptomen sollte die GC-Therapie unmittelbar beginnen; bei PMR und TAK kann sie meistens erst nach Diagnosesicherung erfolgen. Zielgerichtete Therapien wie IL-6-Rezeptor-Inhibitoren (Tocilizumab, Sarilumab) und Upadacitinib erweitern die Optionen bei PMR und RZA. In der Schweiz werden diese Substanzen bei PMR allerdings meist off-label eingesetzt. Grundsätzlich wird für alle TAK-Patienten frühzeitig eine nichtbiologische GC-sparende Therapie empfohlen. Rezidive werden multimodal (Klinik, Labor und wenn notwendig mittels Bildgebung) beurteilt. Generell sollte die Therapie nach Möglichkeit immer individuell und zielgerichtet erfolgen.

Objectives: The GUSTO [GCA treatment with Ultra-Short glucocorticoids (GC) and TOcilizumab] trial was set up to evaluate the efficacy and safety of a 52-week tocilizumab (TCZ) monotherapy after a 3-day GC-pulse in new-onset GCA. The presented data show the maintenance effect of the GUSTO protocol over 3 years and the effectiveness or retreatment with TCZ after relapse. Methods: Eighteen patients with newly diagnosed GCA received 500 mg methylprednisolone i.v. for three consecutive days followed by TCZ monotherapy from day 3 until week 52 in a single-arm, single-centre, open-label clinical trial. Patients in clinical remission stopped TCZ at week 52. Maintenance of efficacy included the proportion of patients with complete lasting remission of disease at week 208. Results: Median age was 72 (interquartile range 67–75) years at inclusion and 15/18 patients complained of cranial symptoms. At week 52, 13/18 patients were in relapse-free remission and entered the follow-up study. Minor relapses were observed in 2/13 patients at weeks 72, 187 and 200. In both patients, remission was achieved after restart of TCZ monotherapy. At week 208, 11/18 patients stayed in relapse-free remission; 11/13 patients remained in drug-free remission for 156 weeks. Conclusion: Drug-free remission was maintained in all but two patients entering long-term extension. This relapse rate is substantially lower than reported in the randomized controlled trials. Patient characteristics (exclusively new diagnoses), and the intensive initial treatment may explain the lasting remission.

Purpose of the Review: Glucocorticoid (GC) toxicity is a major concern in the management of giant cell arteritis (GCA). Tocilizumab (TCZ) has been introduced as a GC-sparing agent in GCA. This review critically analyses the extent of the GC-sparing capacity of TCZ and explores its impact on molecular and imaging findings. Recent Findings: Two randomized controlled trials investigated the GC-sparing potential of TCZ in the treatment of GCA. Four Proof-of-concept studies have investigated the extent to which GC exposure can be further minimized. Recent evidence highlights the chronicity of GCA, emphasizing the need for low-toxicity treatment strategies and advocating for long-term follow-up. Summary: Reducing GC toxicity is one of the most important trends in the management of GCA. New treatment strategies include TCZ and reducing GC exposure and toxicity in patients diagnosed with GCA.

Objectives: MRI is well established for diagnosing GCA. Its role in monitoring disease activity has yet to be determined. We investigated vascular and musculoskeletal inflammation using MRI in the patients of the GUSTO trial to assess the utility of MRI in monitoring disease activity. Methods: Eighteen patients with newly diagnosed GCA received 500 mg methylprednisolone intravenously for three consecutive days followed by tocilizumab monotherapy from day 3 until week 52. Cranial, thoracic and abdominal MRI exams were performed at baseline (active, new-onset disease), and at weeks 24, 52 (remission on-treatment) and 104 (remission off-treatment). MRI findings typical for PMR as well as extent and severity of vasculitic disease were rated. Results: In total, 673 vascular segments and 943 musculoskeletal regions in 55 thoracic/abdominal MRI and 490 vascular segments in 49 cranial MRI scans of 18 patients were analysed. Vasculitic vessels were still detectable in one in four cranial segments at week 24. At weeks 52 and 104, no cranial vascular segment showed a vasculitic manifestation. Large vessels, except for the ascending aorta, and PMR displayed little or no decrease in inflammatory findings over time. Conclusion: Vasculitic manifestations in the cranial vessels normalized after 52 weeks of treatment, whereas large vessel and PMR findings persisted despite lasting full remission. The dynamics of cranial vessel signals suggest that MRI of these arteries might qualify as a potential diagnostic tool for monitoring disease activity and for detecting relapse after 52 weeks of treatment.

This work aimed to investigate a potential link between serum IL-1β levels in patients with giant cell arteritis (GCA) and their responsiveness to combined anti-IL-6 receptor (IL-6R) and glucocorticoid (GC) treatments within the context of two separate clinical trials. IL-1β levels were analyzed in serum samples of two prospective clinical trials investigating tocilizumab in GCA patients using quantitative Polymerase Chain Reaction (qPCR) based Proximity Ligation Assays (PLA). In the phase II randomized controlled trial, serum samples from five patients were quantified at two critical time points: the commencement of the trial (Week 2) and the conclusion of the trial (Week 52). In the GUSTO trial, serum samples from nine patients were similarly analyzed using PLA at Day 0 and Week 52. Furthermore, for the GUSTO trial, serum samples from 18 patients were assessed for IL-1β and IL-1RN at six time points: days 0, 3, and 10, weeks 4, 24, and 52 by a second assay (Proximity Extension Assay, PEA). PLA results from both studies indicated that IL-1β levels were below 1 pg/mL in most of the patients, resulting in notable signal deviations within the same samples. In the analysis of the GUSTO trial, both PLA and PEA exhibited similar trends in IL-1β variations among patients from day 0 to week 52. Notably, the PEA analysis did not show significant variation over time. Furthermore, we did not find a correlation of IL-1β levels with active disease as compared to remission, but interestingly, the measurement of IL-1β receptor antagonist (IL-1RN) revealed a substantial decrease over time. Our study shows that IL-1RN but not IL-1β concentration in serum samples could be directly related to anti-IL-6R treatment in patients diagnosed with GCA.