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Advances in Giant Cell Arteritis

Philip Seo, MD, MHS  |  

The latest research on imaging & treatment for GCA presented at ACR Convergence 2025

CHICAGO—Giant cell arteritis (GCA) is the most common form of systemic vasculitis in older adults, but until recently, we had relatively little to offer patients with this diagnosis. Recent years have seen an explosion of research, leading to substantial advances in the assessment and treatment of GCA. Here, we highlight some of the most exciting GCA-related research presented at ACR Convergence 2025.

1. Efficacy & Safety of Upadacitinib

Schmidt et al., Abstract 07761

In April, the U.S. Food & Drug Administration (FDA) approved upadacitinib, an oral Janus kinase (JAK) inhibitor, for the treatment of GCA based on SELECT-GCA, a double-blind trial. This study demonstrated that 15 mg of upadacitinib taken daily combined with a 26-week glucocorticoid taper was superior to treatment with a 52-week glucocorticoid taper at achieving sustained remission in patients with GCA.2

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In a follow-up study presented from Schmidt et al., patients who remained on upadacitinib for an additional year had a higher sustained remission rate than patients who stopped therapy (68.6% vs. 28.6%), leading to a 90% reduction in the risk of disease flare from week 52 to week 104. Patients who remained on upadacitinib continuously for two years also required less glucocorticoids to remain in remission than patients who stopped therapy after one year. Also, patients treated with 15 mg of upadacitinib daily over two years had higher rates of herpes zoster and elevated creatinine kinase, but lower rates of serious infection, and no increased risk of venous thromboembolism, major adverse cardiovascular events or death.1

Many of clinicians have been reluctant to consider prescribing JAK inhibitors for older patients, given that the ORAL Surveillance clinical trial demonstrated a potential association between tofacitinib and several adverse events, including venous thromboembolism and major adverse cardiovascular events.3 However, the current study with two-year follow-up data from the SELECT-GCA trial implies that long-term therapy with upadacitinib is well tolerated. This finding is fortunate because the results also indicate that relapse occurs within a few months of stopping drug therapy. 

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2. Glucocorticoid Tapering

Buttgereit et al., Abstract 08954

In another analysis, investigators from the SELECT-GCA study focused on the effect of upadacitinib on serious infections, herpes zoster and opportunistic infections.

During the first six months of the study in which patients were treated with glucocorticoids, the addition of upadacitinib did not increase the rate of serious infections (difference -0.3 events/100 person-years; 95% confidence interval [CI] -5.4, 4.8). During the second phase of the study in which patients treated with upadacitinib had already completed their glucocorticoid taper, the rate of infections was higher for patients who were still being treated with glucocorticoids. However, the difference between these two groups was not statistically significant (-4.6 events/100 person-years; 95% CI -11.1, 2.0).

Only four opportunistic infections were noted among patients treated with 15 mg of upadacitinib daily, three of which occurred while the patients were still taking glucocorticoids. The rates of herpes zoster were the same in all groups, both before and after glucocorticoid tapering.

Overall, the message of this study seems to be that the risk of serious infection among patients with GCA is linked to their use of glucocorticoids. Shortening the length of their glucocorticoid taper by using more targeted immunosuppression may reduce that risk.

Meta analyses have associated upadacitinib with an increased risk of herpes zoster.5 The two studies based on SELECT-GCA imply that both upadacitinib and glucocorticoids increase the risk of herpes zoster infection among patients with GCA, and that increased risk persists among patients who remain on upadactinib for remission-maintenance. Reassuringly, the risk of other opportunistic infections seems low.

3. Methotrexate vs. Tocilizumab

Samson et al, Abstract 08916

Randomized clinical trials have supported the use of both methotrexate and tocilizumab in patients with GCA. But the efficacy of these agents have not previously been studied against each other in a single randomized trial. METOGiA was an open-label clinical trial of 218 patients with GCA, 74% with new-onset disease and 26% with relapsing disease. Patients were randomized to receive either 162 mg of subcutaneous tocilizumab weekly or 0.3 mg/kg of methotrexate—but no more than 20 mg weekly—for 52 weeks in addition to a glucocorticoid taper of 42 weeks for patients with new onset GCA and 36 weeks for patients with relapsing disease. The study’s primary outcome was the proportion of patients without relapse measured at week 78, which was 26 weeks after treatments were discontinued.

By week 78, more patients treated with tocilizumab remained relapse-free while adhering to the prespecified prednisone taper than patients who were treated with methotrexate (46% vs. 37%). The difference between the two groups was not statistically significant (9% difference, 95% CI -4%, 22%). Five patients treated with methotrexate developed Pneumocysitis infection. Altogether, seven deaths occurred in the study, six of which were in patients treated with methotrexate.

Secondary analyses demonstrated that, at week 52, more patients treated with tocilizumab were relapse-free while tapering to prednisone ≤5 mg/d (81% vs. 56%). However, by week 78, approximately equal numbers of patients in both groups met these criteria (50% vs. 58%).

For patients with GCA treated with glucocorticoids for one year, we expect to see a relapse rate of approximately 50%. This subgroup analysis implies that patients treated with methotrexate experience many of these relapses upfront, whereas patients treated with tocilizumab do not begin to relapse in earnest until after they stop tocilizumab therapy.

This study does not address whether methotrexate may be more effective as a remission-maintenance agent, following remission-induction with tocilizumab.7 However, for those of us who have used methotrexate as a safe alternative to tocilizumab for remission-induction in patients with GCA, methotrexate’s association with Pneumocystis infection and increased mortality is foreboding.

4. Vascular Ultrasound in GCA

Ni et al, Abstract 27028

Vascular ultrasound is becoming increasingly popular as an alternative to temporal artery biopsy for diagnosing GCA. However, the majority of data supporting its use was generated by physicians who performed the ultrasound themselves. The current study examined the efficacy of vascular ultrasound when performed by radiology technicians.

In the study, 581 patients underwent vascular ultrasound; 80 of these patients (21.3%) had a confirmed clinical diagnosis of GCA after six months of follow-up. Using a clinical diagnosis of GCA as the gold standard, vascular ultrasound had a sensitivity of 21.3% and a specificity of 100%. The negative predictive value of vascular ultrasound was 82.4%.

When performed by an experienced clinician, vascular ultrasound has a sensitivity approaching temporal artery biopsy. However, the same cannot be said when the test is performed by a vascular ultrasound technician who may not have specific training in the assessment of GCA. Carotid arteries are assessed mainly based on flow dynamics, which are not useful when trying to determine if a patient has an inflamed temporal artery.

For years, rheumatologists have known that musculoskeletal ultrasound is most effective when performed by a clinician who understands the underlying disease and its pathology. It shouldn’t be surprising to learn that the same is true for temporal artery ultrasound.

5. Glucocorticoids vs. Glucocorticoids Plus Tocilizumab

De Boysson et al., Abstract 27049

Patients with GCA may have histopathologic evidence of arterial inflammation years after treatment initiation. Such patients are at higher risk of developing potentially life-threatening aneurysms.10 However, whether some therapies are more effective at extinguishing this chronic arterial inflammation has remained unclear.

This study examined 115 patients with GCA who had evidence of large vessel vasculitis at diagnosis based on positron emission tomography (PET) scan with a computed tomography (CT) scan. The study found that more patients treated with tocilizumab and glucocorticoids demonstrated resolution of inflammation than patients treated with glucocorticoids alone (76% vs. 41%).

Aortic aneurysms are one of the most feared complications of GCA and may occur years after the initial diagnosis, even among patients whose disease seems to be well controlled. This study implies that treatment with tocilizumab may decrease chronic aortitis among patients with GCA, leading to better long-term outcomes. However, it is still unclear whether PET/CT scan is an appropriate surrogate marker because other studies have demonstrated no association between fluorodeoxyglucose/PET activity and long-term outcomes.11

6. Cranial MRI in Relapsing GCA

Zeng et al., Abstract 270312

Relatively few objective methods exist for diagnosing relapse in a patient with a known history of GCA. This study examined the use of cranial vessel wall magnetic resonance imaging (MRI) as a marker of relapse.

In this study, four patients with a cranial or ocular relapse of GCA had evidence of increased vascular wall MRI enhancement in at least one cranial structure. In two of these patients, the MRI changes preceded clinical evidence of disease flare. Two patients who experienced a relapse comprising polymyalgia rheumatica without cranial symptoms had persistent, but not increased, enhancement, whereas seven of eight patients in sustained remission had decreased or normal enhancement on follow-up.

One of the greatest challenges when managing a patient with GCA is distinguishing a cranial relapse from other causes of headache. Preliminary, this study implies that direct visualization of the temporal artery through MRI may be the answer to this conundrum and potentially spare many patients needless courses of empiric glucocorticoids.

7. The Glucocorticoid Burden & The Perception of Advanced Therapies

Dua et al., Abstract 073813

Multiple studies have demonstrated the efficacy of several agents for the treatment of GCA and the harms associated with chronic glucocorticoid therapy. This study examined the impact of these findings on clinical care by surveying the practice patterns of 189 rheumatologists from the U.S., the EU and the UK. These rheumatologists completed patient record forms on 846 patients with GCA.

Overall, most rheumatologists agreed that most patients should be given advanced therapies, such as tocilizumab or methotrexate, early in the disease course and should be tapered off of glucocorticoids after two years. However, the patient record forms indicated that the median time from diagnosis to receiving tocilizumab or methotrexate was approximately five months. Also, after four years of treatment, 75% of patients continued to take low-dose prednisone (5.3 mg/day).

This study highlights the gap between clinical research and clinical practice. The harms associated with the use of even low-dose glucocorticoids have become clearer just as we have developed alternate therapies for GCA that are safe and effective. Despite these advances, many patients use advanced therapies only after failing glucocorticoid monotherapy and use low-dose glucocorticoids to maintain remission. This approach may be driven by a number of factors, including physician and patient preferences, and the EULAR guidelines, which advocate for the use of advanced therapies mainly in patients with relapsing or refractory disease.14

Philip Seo, MD, MHS

Philip Seo, MD, MHS, is an associate professor of medicine at Johns Hopkins University School of Medicine. He served as the third physician editor of The Rheumatologist.

References

  1. Schmidt W, Setty A, Dejaco C, et al. Efficacy and safety of upadacitinib in giant cell arteritis: 2-year results from the re-randomized, double-blind SELECT-GCA phase 3 trial. [abstract 0776]. Arthritis Rheumatol. 2025;77(suppl 9).
  2. Blockmans D, Penn SK, Setty AR, et al. A phase 3 trial of upadacitinib for giant-cell arteritis. N Engl J Med. 2025 May 29;392(20):2013–2024.
  3. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022 Jan 27;386(4):316–326.
  4. Buttgereit F, Winthrop K, Calabrese L, et al. Impact of glucocorticoid tapering in giant cell arteritis: analysis from the SELECT-GCA trial [abstract 0895]. Arthritis Rheumatol. 2025;77(suppl 9).
  5. Burmester GR, Deodhar A, Irvine AD, et al. Safety profile of upadacitinib: descriptive analysis in over 27,000 patient-years across rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and inflammatory bowel disease. Adv Ther. 2025 Oct;42(10):5215–5237.
  6. Samson M, Bourredjem A, Outh R, et al. methotrexate versus tocilizumab for treatment of giant cell arteritis (METOGiA trial): A multicenter, randomized, controlled trial [abstract 0891]. Arthritis Rheumatol. 2025;77(suppl 9).
  7. Schäfer V. Methotrexate as remission maintenance therapy after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis (MTXinGCA) [NCT05623592]. ClinicalTrials.gov. 2024 Oct 04.
  8. Ni R, Langford R, Kohler M, et al. Diagnostic performance of vascular ultrasound in giant cell arteritis—a single center experience [abstract 2702]. Arthritis Rheumatol. 2025;77(suppl 9).
  9. De Boysson H, Dumont A, Orvain T, et al. Complete metabolic response on PET/CT in giant-cell arteritis-related large vessel vasculitis : Comparison of two strategies using glucocorticoids or glucocorticoids + tocilizumab [abstract 2704]. Arthritis Rheumatol. 2025;77(suppl 9).
  10. Kaymakci MS, Boire NA, Bois MC, et al. Persistent aortic inflammation in patients with giant cell arteritis. Autoimmun Rev. 2023 Sep;22(9):103411.
  11. Quinn KA, Ahlman MA, Grayson PC, et al. Use of 18F-fluorodeoxyglucose positron emission tomography to monitor disease activity in patients with giant cell arteritis on tocilizumab. ACR Open Rheumatol. 2025 Feb;7(2):e11797.
  12. Zeng R, Rebello R, Guggenberger K, et al. Longitudinal changes on cranial magnetic resonance imaging in relapsing giant cell arteritis [abstract 2703]. Arthritis Rheumatol. 2025;77(suppl 9).
  13. Dua A, Kadakia A, Zueger P, et al. Real world steroid burden, treatment patterns and rheumatologists’ perceptions on advanced therapy in giant cell arteritis [abstract 0738]. Arthritis Rheumatol. 2025;77(suppl 9).
  14. Hellmich B, Agueda A, Monti S, et al. 2018 update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79(1):19–30.