Giant Cell Arteritis - �Evolving Paradigms in Diagnosis and Treatment

Aladdin Mohammad, MD, MPH, PhD

Professor, Senior Consultant

Department of Rheumatology, Skåne University Hospital, Lund, Sweden

Clinical Sciences, Rheumatology, Lund University, Lund, Sweden

Visiting Researcher, Department of Medicine, University of Cambridge,

Cambridge, UK

21 November 2025

Abu Dhabi - UAE

Disclosures

• Lecture fees, consultations, research fonds and advisory boards
• AbbVie
• AMGEN
• AstraZeneca
• Boehringer Ingelheim
• CSL Vifor
• Eli Lilly Sweden
• GSK
• Novartis
• Roche Sweden

The first documented clinical description is attributed to Ali ibn Isa, a physician from Baghdad in the 10th century.

Temporal Arteritis

GCA is not a new disease

Yet our understanding of it is changing rapidly.

Ross RT J Neurol Neurosurg Psychiatry. 1988;51(4):528-.

Wood CA. Northwestern University Press. 1936;1936:225.

Chapel Hill Consensus Conference 2012

Jennette et al. Arthritis Rheum. 2013;65(1):1-11.

Definition of GCA

CHCC 1994

Global Incidence of GCA

3.2

12.7

9.4

19.8

1.1

10

13.3

10.1

8.1

22.2

7.4

10

3.2

43.6

16.8

5.8

Watts et al. Nat Rev Rheumatol. 2022 Jan;18(1):22-34.

Stamatis P et al. Rheumatology (Oxford). 2021;61(1):146-153.

Incidence of biopsy-proven GCA in Sweden

Epidemiology of biopsy-proven giant cell arteritis (GCA) in Sweden

Stamatis P et al. Rheumatology (Oxford), 2021;61(1):146-153.

Watts et al. Nat Rev Rheumatol. 2022;18(1):22-34.

Changing incidence of TAB+GCA

Incidence of biopsy-proven GCA in Sweden

Incidence of biopsy-proven GCA is declining by ~2% per year.

Distribution of large vessel and cranial artery involvement in giant cell arteritis

KSM van der Geest et al. Lancet Rheumatol 2024;6: e397–408

Diagnosis of Giant Cell Arteritis

GCA- signs and symptoms

Eye (2020) 34:1013–1026

Cranial GCA

Large vessel GCA

• New onset headache
• Scalp tenderness
• Jaw claudication
• Visual problems
• Amaurosis fugax
• Temporal a. abnormalities
• Proximal muscle pain/ stiffness
• Fever, anaemia
• Inflammatory parameters

• Chest pain
• Abdominal pain
• Fever
• Fatigue
• Limb claudication
• Weight loss

Diagnosis of Giant Cell Arteritis

Mackie et al. Rheumatology 2020;59:e1–e23

Diagnosis of Giant Cell Arteritis

Fast Track Clinic (FTC)

• Predictors of positive TAB according to different studies

Walvick M, Ophthalmology. 2011 Jun;118(6):1201-4.

Temporal artery biopsy (TAB)

• Key diagnostic tool in suspected GCA; gold standard for temporal arteritis
• Sensitivity ~30–40%. Improves with biopsy >10 mm and <7 days steroid use
• Should be considered in all clinically suspected cases.

• Predictors
• Older age
• Female sex
• Jaw claudication
• Abnormal temporal artery

• Predictors
• Weight loss
• Short GC exposure
• ↑1.5× with ESR 47–107 mm/hr

Dejaco et al. Ann Rheum Dis. 2024;83(6):741-751. 

Summary of EULAR recommendations 2023

Imaging in GCA at diagnosis

Imaging in GCA

Conventional angiography is not recommended for the diagnosis of GCA

Imaging studies in GCA and LVV

PET CT

US

CTA

MRI

Dalsgaard Nielsen B.

Eur J Nucl Med Mol Imaging. 2018;45(7):1119-1128.

New PET CT

Partial regression of vasculitis with some areas of mild hypermetabolism

June, 2017

July, 2017

New 2026

New 2026

Treatment of Giant Cell Arteritis

Phase I

Phase II

Hellmich B, et al. Ann Rheum Dis 2020;79:19–30.

• High-dose steroids (40–60 mg/day) should begin without delay in active GCA.
• Once disease is controlled, Prednisolone tapered to a target dose of:
• 15–20 mg/day within 2–3 months

​

• ≤5 mg/day after 1 year

​

• 0 mg over 12–18 months*

​

*Providing there is no return of symptoms, signs or lab markers of inflammation.

Oral Glucocorticosteroids (GC)

Hellmich B, et al. Ann Rheum Dis 2019;0:1–12.

Mackie et al. Rheumatology 2020;59:487–494

Intravenous Methylprednisolone (IV MP)

• Indications
• GCA with acute visual loss or amaurosis fugax
• Dose?
• 0.25–1 g I.V. MP for up to 3 days

​

• 0.5–1 g I.V. MP for up to 3 days

​

• Referral for IV GC therapy should not delay treatment with oral GC*
• *60-100mg oral prednisolone may be given for up to 3 consecutive days

​

Hellmich B, et al. Ann Rheum Dis 2019;0:1–12

Mackie et al. Rheumatology 2020;59:487–494

I. Small RCT (27 TAB+ GCA patients) IVMP vs. Placebo

• Studied impact on cumulative GC dose and remission with low-dose GC
• Not designed to assess vision or ischemic complications

II. Observational study (84 patients, OGC ± IVMP):

• Visual improvement: 7% IVMP vs. 5% oral (p=0.672)
• Patients with improvement had shorter interval from visual loss to therapy start (p=0.065)

​

Mazlumzadeh M et al. ARTHRITIS & RHEUMATISM. 54,10, 2006, pp 3310–3318

Do we have evidence to recommend IV MP in GCA?

​

Hayreh et al. Acta Ophthalmol Scand. 2002 Aug;80(4):355-67.

Surprisingly, the evidence supporting the use of IVMP in GCA is low

IVMP in GCA – Two key Studies

Patients

• 419 patients (69% female)
• 184 had visual manifestations
• 104 were treated with IVMP
• 80 received OGCs only

IVMP in GCA

Henningsson H. et al. Rheumatology (Oxford). 2025;64(4):2083-2090.

Diabetes-free survival

Patients' survival

• Compared to OGC, IVMP-treated patients:
• Showed a trend toward improved VA (OR 1.19, 95% CI 0.35–4.01),
• A higher risk of new-onset diabetes within one year (OR 2.59, 95% CI 1.19–5.63)
• No difference in survival.

Patients

• 419 patients (69% female)
• 184 had visual manifestations
• 104 were treated with IVMP
• 80 received OGCs only

IVMP in GCA

Henningsson H. et al. Rheumatology (Oxford). 2025;64(4):2083-2090.

Diabetes-free survival

Patients' survival

• Compared to OGC, IVMP-treated patients:
• Showed a trend toward improved VA (OR 1.19, 95% CI 0.35–4.01),
• A higher risk of new-onset diabetes within one year (OR 2.59, 95% CI 1.19–5.63), and
• No difference in survival.

• Time to reconsider our GC strategy in GCA!
• Critical unmet need: RCTs!

Hellmich B, et al. Ann Rheum Dis 2019;0:1–12

Mackie et al. Rheumatology 2020;59:487–494

Methotrexate for GCA

Consider TCZ in refractory or relapsing GCA, or when GC toxicity risk is high; MTX can be used as an alternative, particularly during GC tapering

At present, the only synthetic DMARD with any evidence for GC-sparing in GCA is MTX.

Biologics for GCA

is NOT recommended by any of the guidelines to be used in GCA

Data on adjunctive Abatacept therapy in GCA are limited, and the drug is not currently approved for this indication.

Anti-TNF-α

Abatacept

The GCAptAIN study did not meet its primary endpoint. Disappointing! 

Secukinumab

Stone et al. N Eng J Med 2017; 377: 317-28

1

2

3

4

1

2

3

4

Sustained remission

Serious adverse E&

severe infections

GiACTA

Tocilizumab

Consider TCZ as adjunctive therapy during GC tapering in GCA, particularly in refractory, relapsing, or GC-intolerant cases.

Stone JH et al. Rheumatology 2022;61:2915–2922

GiACTA 3-year extension

Time to first flare after clinical remission

GiACTA Extension

New onset vs. Relapsing GCA

Relapsing GCA

New onset GCA

QW

Q2W

QW

Q2W

Stone JH et al. Rheumatology 2022;61:2915–2922

GiACTA 3-year extension

Time to first flare after clinical remission

TCZ dosed weekly delayed time to first flare to a greater degree than every-other-week dosing.

GiACTA 3-year extension

Stone JH et al. Rheumatology 2022;61:2915–2922

Cumulative GC exposure

Pred

TCZ

These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA.

TCZ weekly (QW) lowered cumulative glucocorticoid use in both relapsing and new-onset GCA.

Adler S et al. Rheumatology (Oxford) 2019;58(9):1639-1643

• After TCZ withdrawal:
• ~50% remained in remission at 1 year
• Others relapsed within months
• No predictors of relapse or sustained remission identified

Villiger PM et al. Lancet 2016;387(10031):1921-7.

Samson M et al. Arthritis Rheumatol. 2025; 77 (suppl 9).

*ITT population

• TCZ outperformed MTX in sustaining remission and preventing relapse, though MTX matched remission rates with low-dose prednisone.

METOGiA

Methotrexate or Tocilizumab?

• Objectives To assess the efficacy and safety of UPA vs. placebo (PBO), in combination with a GC taper regimen, in patients with GCA.

​

• UPA 15 mg N=209
• UPA 7.5 mg N=107

​

• Placebo N=112

​

Blockmans D et al. N Engl J Med. 2025;392(20):2013-2024

• Methods A double-blind, randomized PBO-controlled phase 3 trial
• 428 patients were randomized: (New-onset GCA: 70%, Relapsing GCA: 30%)

26-week GC taper

52-week GC taper

SELECT-GCA

Upadacitinib in GCA

Blockmans D et al. N Engl J Med. 2025;392(20):2013-2024

Proportion of subjects achieving sustained remission from Week 12 through Week 52.

Significantly higher proportion of patients receiving UPA 15 mg achieved sustained remission versus PBO at week 52

Blockmans D at el. Annals of the Rheumatic Diseases 2024;83:232-233.

SELECT-GCA

Upadacitinib in GCA

• Safety
• Higher rates of serious infections and MACE observed in the PBO group, and no MACE reported in the UPA groups.
• Rates of:
• Herpes zoster, lymphopenia, anemia, and nonmelanoma skin cancer (NMSC) numerically higher with UPA15 than PBO.
• VTE: comparable across groups.
• Malignancy, excluding NMSC, were similar between UPA15 and PBO.
• Deaths: two in the PBO group and two in the UPA15 group

Blockmans D et al. N Engl J Med. 2025;392(20):2013-2024

SELECT-GCA

Upadacitinib in GCA

• Safety
• Higher rates of serious infections and MACE observed in the PBO group, and no MACE reported in the UPA groups.
• Rates of:
• Herpes zoster, lymphopenia, anemia, and nonmelanoma skin cancer (NMSC) numerically higher with UPA15 than PBO.
• VTE: comparable across groups.
• Malignancy, excluding NMSC, were similar between UPA15 and PBO.
• Deaths: two in the PBO group and two in the UPA15 group

Blockmans D et al. N Engl J Med. 2025;392(20):2013-2024

Upadacitinib 15 mg/day is effective and safe in GCA

SELECT-GCA

Upadacitinib in GCA

Autoimmunity Reviews 23 (2024) 103580

Relapse in GCA

• Major relapse
• Severe ischemic events, or
• Active LV inflammation causing structural damage

• Minor relapse
• Relapses not meeting major criteria

• Relapses
• Are frequent (>40% of GC-only treated patients)
• Mostly occur within the first 2 years after diagnosis.

Treatment:

Increase in GC dose to the last effective dose

Treatment:

As new onset disease

Wadström K et al. Rheumatology (OXFORD). 2020;59(11):3229-3236.

In this population-based nested case–control study from the Malmö Preventive Medicine Project, individuals who later developed GCA had significantly lower fasting blood glucose, cholesterol, and triglyceride levels at baseline compared with matched controls.

The metabolic profile prior to GCA (Pre-GCA)

Wadström et al. Arthritis Res Ther. 2024 ;26(1):37.

In this nested case–control study from the Malmö Diet and Cancer cohort, individuals who later developed GCA had significantly higher baseline levels of apolipoprotein A-I, while ApoB levels were similar to controls.

The metabolic profile prior to GCA (Pre-GCA)

Kwanyuen P et al. Arthritis Rheumatol. 2024;76 (S9): abstract #1613

High adherence to dietary guidelines, characterized by low sugar intake, high consumption of fiber, fish, and vegetables, was associated with an increased risk of subsequently developing GCA.

The metabolic profile prior to GCA (Pre-GCA)

If

You have normal fasting blood sugar

You have normal or low cholesterol, Triglycerides and higher level of apolipoprotein A-I

You eat a healthy diet

GCA!

• Individuals who later develop GCA tend to have a healthier metabolic profile!
• A metabolic profile associated with lower risk of cardiovascular disease may predispose to GCA.

You may get

Stamatis et al. RMD Open. 2024 Apr 10;10(2):e003960.

Myocardial infarction in GCA

Stroke in GCA

Stratified by time from date of GCA diagnosis

Jóhannsdóttir G et al.- Vasculitis Workshop

-Barcelona- April 2024

Tabakovic D et al.- Vasculitis Workshop

-Melbourne February 2026

Atrial Fibrillation in Patients with Giant Cell Arteritis compared to the General Population

Atrial fibrillation in GCA

Incidence of Cardiovascular comorbidities in GCA (Post-GCA)

• CVEs occurred early during the disease course
• Can we do better?

Antiplatelet/Anticoagulants in GCA

Hellmich B, et al. Ann Rheum Dis 2019;0:1–12

Mackie et al. Rheumatology 2020;59:487–494

Not routinely recommended in LVV or GCA due to insufficient evidence, but may be considered in cases of vascular ischemia or high cardiovascular risk.

• The incidence of TAB-positive GCA is declining.
• A likely explanation is increased use of imaging.

• Three main disease phenotypes
• Diagnosis based on clinical features, imaging and TAB

Epidemiology

Diagnosis of GCA

Fast Track Clinics

• FTC is likely to become the future standard of care.

In summary

• Oral GC remain first line treatment
• IV methylprednisolone likely offers no benefit

• The only approved is Tocilizumab (IL6i)
• Other biologics
• TNFi NO!
• Abatacept may be!
• Secukinumab NO!

Glucocorticosteroids

Biologics

Targeted therapies

• Upadacitinib is the most promising new agent

In summary

Comorbidities

• Action needed to prevent CVDs

Thank You for your attention!

A sunny, snowy morning in Lund!