Read Part 1: Giant Cell Arteritis: Diagnosis: https://thischangedmypractice.com/giant-cell-arteritis-part-1-diagnosis/.
What care gaps or frequently asked questions have we noticed?
This article is the second of a two-part series on the diagnosis and treatment of giant cell arteritis (GCA). Please see Part 1 for information on the diagnosis of GCA.
GCA is a form of large vessel vasculitis that can lead to significant morbidity. All patients with suspected GCA need urgent assessment for investigations, treatment, and for monitoring complications. Treatment with glucocorticoids should be initiated upon clinical suspicion of GCA. Although patients with GCA respond very well to high-dose glucocorticoids, between 34-75% of patients will experience a relapse during their prednisone taper.1 Prevention and appropriate management of relapses is an important aspect of caring for patients with GCA. Each relapse increases total glucocorticoid exposure, thus increasing the burden of adverse glucocorticoid effects. Overall, the treatment of GCA requires an individualized approach focussed on maintaining remission while mitigating the adverse effects of glucocorticoids.
This article provides a practical approach to the treatment of GCA, based on current evidence and local practice patterns. We will review the following commonly encountered topics:
- The timing, dosing, and choice of initial therapy.
- Prednisone taper schedule.
- Recognition and treatment of relapses, including the use of steroid-sparing therapy.
- The role for adjunctive therapies, including aspirin, jirovecii pneumonia prophylaxis, and bisphosphonates.
Data that answers these questions or gaps
Initiation of treatment:
Treatment with high-dose glucocorticoids should be initiated immediately upon clinical suspicion of GCA. The treatment should not be delayed to facilitate the temporal artery biopsy. Glucocorticoids are the gold-standard agents for GCA. Patients who present with ischemic complications such as vision loss, amaurosis fugax, or stroke should receive pulse steroids with methylprednisolone 500-1000 mg IV daily for 3 days, followed by 60 mg of prednisone daily, although the evidence for this is sparse.1,2 For patients without ischemic complications, Prednisone 40-60 mg should be started. We do not recommend starting doses higher than 60 mg regardless of the patient’s weight. We recommend tapering prednisone after 2-4 weeks of initiation. If the patient fails to improve with high-dose prednisone, consideration of an alternative diagnosis should be made.
There is no high-quality evidence comparing different tapering schedules in patients with GCA. In most cases, prednisone should be tapered to less than 20 mg a day within 2 months. From the initial dose of 40-60 mg, we suggest lowering the dose by 10 mg every 2 weeks until a dose of 20 mg is reached, followed by reducing the dose by 2.5 mg every 2 weeks until 10 mg is reached. From 10 mg, the dose should be decreased by 1 mg every 2-4 weeks. Patients should ideally be on doses less than 5 mg by the 1-year mark. Anecdotally, many patients will require prednisone for up to 2 years. Patients should be dosed with prednisone daily, as dosing on alternate days is associated with higher rates of relapse.3
Relapses are common during prednisone tapers and tend to occur at doses under 15 mg daily. Distinguishing between major and minor relapses is important, as management will differ for each. Major relapses are defined by evidence of ischemia, including jaw claudication, visual symptoms, scalp necrosis, stroke, or limb claudication.1 The development of aortitis would also be classified as a major relapse.1 Minor relapses include recurrence of symptoms without evidence of ischemia or large vessel damage (e.g. headaches, scalp tenderness, polymyalgia rheumatica).1
For major relapses, patients should be treated similar to new-onset GCA, with prednisone 40-60 mg per day, followed by a taper in the usual fashion.1,2 For minor relapses, prednisone should be increased to the last effective dose or 5-15 mg above their current dose.1,2 If the patient was not placed on a steroid-sparing agent as upfront therapy, we recommend initiating one at the time of relapse (see below).1,2
Rising inflammatory markers (ESR, CRP) in the absence of symptoms of GCA does not necessarily indicate a relapse and should prompt a thorough evaluation for infection or other causes of inflammation. If inflammatory markers are persistently elevated and no other cause is found, vascular imaging should be arranged to rule out large vessel vasculitis, which occurs in approximately 83% of patients with GCA.4 If the work-up for other causes of inflammation and large vessel imaging is negative, we recommend clinical observation and monitoring without escalation of glucocorticoid therapy. If inflammatory markers continue to rise, the patient should be treated as a minor relapse.
There is significant morbidity associated with the cumulative glucocorticoid exposure used in GCA, especially since this disease affects the older population. One study found that 86% of patients treated for GCA developed adverse glucocorticoid effects such as diabetes, osteoporotic fractures, gastrointestinal bleeding, hypertension, infections, and cataracts at an average follow-up interval of 10 years.5
Currently, there is some evidence for both tocilizumab and methotrexate as steroid-sparing agents for the treatment of GCA.6-10 Leflunomide is also considered useful by most experts, although its evidence in GCA is sparse. These agents should be initiated by a rheumatologist, and used in conjunction with a prednisone taper. Tocilizumab has been shown to reduce total glucocorticoid exposure as well as risk of relapse in patients with GCA.6,7 Methotrexate has demonstrated modest reductions in relapse risk and steroid-sparing effects.8-10. In British Columbia, tocilizumab is restricted to patients who fail methotrexate or leflunomide.
The upfront use of steroid-sparing therapies should be individualized based on the patient’s clinical phenotype and risk of glucocorticoid toxicity. Patients with evidence of large vessel disease, or those with pre-existing osteoporosis, glaucoma, diabetes, or certain psychiatric comorbidities are often treated upfront with a steroid-sparing agent. This decision should ultimately be deferred to the patient’s rheumatologist. Steroid-sparing agents are recommended in all patients who relapse on glucocorticoid monotherapy.1,2
The 2018 European League Against Rheumatism (EULAR) guidelines on GCA recommends Aspirin 81 mg daily only in patients who present with acute vision loss or stroke.1 When combined with glucocorticoids and advanced age, the addition of ASA increases the risk of gastrointestinal bleeding; thus, patients who receive ASA should also be placed on a proton pump inhibitor (PPI).
To mitigate the risk of glucocorticoid-related osteoporosis and fragility fractures, all patients should be counselled on lifestyle modifications such as weight-bearing activity and resistance training. Oral calcium (1000 to 1200 mg per day) and vitamin D (1000-2000 IU per day) should be initiated in all patients while on glucocorticoids.11 Additionally, given the high cumulative doses of glucocorticoids used in patients with GCA, we typically start patients on anti-resorptive therapy with bisphosphonates or denosumab.11 All patients with a new diagnosis of GCA should have a bone mineral density assessment within 6 months of starting glucocorticoids.11 Anti-resorptive treatment can be discontinued when the patient is off glucocorticoids and deemed low risk by the fracture risk assessment tool (FRAX).11
There is limited evidence to guide the initiation of trimethoprim-sulfamethoxazole for P. jirovecii pneumonia (PJP) prophylaxis in patients with GCA. While PJP in patients with GCA is rare, consideration of prophylaxis in patients should be done on an individual basis, particularly if they have other immunosuppressing comorbidities or medications.12 Caution should be exerted in patients with renal dysfunction.
What we recommend
- All patients with a suspected diagnosis of GCA should be referred to a rheumatologist.
- All patients with a suspected diagnosis of GCA should be immediately initiated on prednisone at a dose of 40-60 mg per day or given methylprednisolone 500-1000 mg daily if there is acute vision loss or stroke.
- Prednisone should ideally be tapered to a dose under 20 mg daily within 2 months of starting treatment.
- Patients who relapse or those at high risk of complications should be started on a steroid-sparing therapy with methotrexate, leflunomide, or tocilizumab.
- Aspirin is only recommended in patients who present with vision loss or stroke.
- All patients on steroids for GCA should be counselled on lifestyle interventions to prevent osteoporosis. Additionally, we recommend pharmacologic therapy with calcium, vitamin D, and bisphosphonates. PPI and PJP prophylaxis should be strongly considered.
- Hellmich B, Agueda A, Monti S, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2019;79(1):19-30. DOI: 10.1136/annrheumdis-2019-215672. (Request with CPSBC or view with UBC)
- Mackie S, Dejaco C, Appenzeller S, et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: executive summary. Rheumatology (Oxford). 2020;59(3):487-494. DOI: 10.1093/rheumatology/kez672. (View with CPSBC or with UBC)
- Mukhtyar C, Guillevin L, Cid M, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2009;68(3):318-323. DOI: 10.1136/ard.2008.088351. (Request with CPSBC or view with UBC)
- Dejaco C, Brouwer E, Mason J, Buttgereit F, Matteson E, Dasgupta B. Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities. Nat Rev Rheumatol. 2017;13(10);578-592. DOI: 10.1038/nrrheum.2017.142. (Request with CPSBC or view with UBC)
- Proven A, Gabriel S, Orces C, O’Fallon W, Hunder G. Glucocorticoid therapy in giant cell arteritis: Duration and adverse outcomes. Arthritis Rheum. 2003;49(5):703-708. DOI: 10.1002/art.11388. (View)
- Villiger P, Adler S, Kuchen S, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10031):1921-1927. DOI: 10.1016/S0140-6736(16)00560-2. (View with CPSBC or with UBC)
- Stone J, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317-328. DOI: 10.1056/NEJMoa1613849. (Request with CPSBC or view with UBC)
- Jover J, Hernández-García C, Morado I, Vargas E, Bañares A, Fernández-Gutiérrez B. Combined treatment of giant-cell arteritis with methotrexate and prednisone. Ann Intern Med. 2001;134(2):106. DOI: 10.7326/0003-4819-134-2-200101160-00010. (Request with CPSBC or view with UBC)
- Hoffman G, Cid M, Hellmann D, et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum. 2002;46(5):1309-1318. DOI: 10.1002/art.10262. (View)
- Buckley L, Guyatt G, Fink H, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum. 2017;69(8):1521-1537. DOI: 10.1002/art.40137. (View)
- Schmidt J, Warrington K. Polymyalgia rheumatica and giant cell arteritis in older patients: diagnosis and pharmacological management. Drugs Aging. 2011;28(8):651-666. DOI: 10.2165/11592500-000000000-00000. (View with CPSBC or with UBC)