Recommendations
Key Recommendations
GCA is a medical emergency and is associated with a risk of permanent sight loss and (more rarely) stroke.[35][36][37]
If GCA is strongly suspected, start treatment with a high-dose glucocorticoid immediately, even while awaiting confirmation of the diagnosis.[36]
Ideally give the first dose of a glucocorticoid immediately after taking a blood sample (because inflammatory markers decrease with glucocorticoid therapy).[36]
Do not delay immediate referral to a specialist (e.g., rheumatology, ophthalmology, neurology) for patients started on pre-emptive treatment because glucocorticoids can decrease the sensitivity of diagnostic tests.[35] In addition, because pre-emptive treatment unnecessarily exposes patients who are eventually found not to have GCA to glucocorticoids, confirming the diagnosis is a priority.[35]
Additional therapeutic options are available for patients who present with recent vision loss or develop significant side-effects from glucocorticoids.
A specialist will consider tocilizumab or methotrexate in combination with a glucocorticoid taper in patients with GCA who relapse, have refractory disease, or who are at high risk of glucocorticoid toxicity.[35][36]
If you strongly suspect GCA, start treatment with a high-dose glucocorticoid immediately while awaiting confirmation of the diagnosis.[36]
This means that you suspect GCA is a more likely diagnosis, based on the patient’s presentation, than any other condition, taking into account the symptoms, signs, and available laboratory test results.[36]
Standard initial treatment for patients is oral prednisolone prescribed in a single daily dose.[35][36]
High-dose therapy is recommended to achieve rapid disease control. Actively consider other diagnoses while awaiting confirmation, and also if patients do not respond within 7 days.[36]
Assess symptoms of and/or exposure to serious infections in all patients starting glucocorticoids, taking local prevalence of infections into account.[36] Ask about exposure to tuberculosis and follow national screening guidelines.[36][60]
Ensure that patients are evaluated for hypertension and hyperglycaemia at the time of starting high-dose glucocorticoids.[36]
Vision loss
More aggressive treatment may be indicated for patients who present with recent vision loss.
In patients with GCA with acute or intermittent visual loss or amaurosis fugax, a specialist may consider giving intravenous methylprednisolone.[35][36]
Referral for intravenous glucocorticoid therapy should not delay starting treatment with an oral glucocorticoid.[35][36]
Vision loss due to anterior ischaemic optic neuropathy (ION) or central retinal artery obstruction from GCA is irreversible. Greater disease awareness and earlier diagnosis probably accounts for a decline in the incidence of permanent visual loss due to GCA.[43][61]
Dose tapering
Guidelines recommend tapering the dose over 12 to 18 months while monitoring for toxicity and relapse.[35][36] Consider a more rapid dose reduction in patients at high risk of glucocorticoid toxicity and/or those receiving concomitant glucocorticoid-sparing therapy.[36] However, there is a lack of good quality evidence on tapering regimens. In our expert’s opinion, most patients need 2 years of prednisolone treatment for GCA.[62]
During prednisolone taper, evaluate the patient regularly by clinical examination and check inflammatory markers periodically. The treatment must be tapered in a safe manner with regular checks for toxicity and relapse. Diagnose a relapse objectively and not on the basis of just a rise in inflammatory markers. Reassess the patient as at baseline for other differential diagnoses and re-evaluate the glucocorticoid tapering plan.
Return of symptoms needs objective assessment for relapsing disease as at diagnosis. The temptation to treat a rise in C-reactive protein or headaches and jaw pain should be avoided. Intensification of immunosuppression must be justified by demonstration of relapsing disease whenever possible. Relapses require a change in the planned glucocorticoid therapy with addition of further immunosuppression in the form of methotrexate or tocilizumab.
Management of glucocorticoid-induced adverse effects
Take measures to avoid possible complications associated with glucocorticoid treatment, such as bone protection with calcium, vitamin D, and bisphosphonates to prevent glucocorticoid-induced bone loss.[39][63] Counselling on lifestyle changes and monitoring may also be required.[63] Also consider providing a proton-pump inhibitor for gastrointestinal protection when prescribing high-dose glucocorticoid therapy. With lower glucocorticoid doses, coprescription of a proton-pump inhibitor may not be needed.[64] Follow your local guidance.[36]
Regularly check HbA1c to identify patients who are becoming diabetic.[36] There is limited evidence that early use of metformin in this group of patients may prevent long-term impairment of glycaemic control.[65]
Long-term treatment with high-dose corticosteroids carries a high risk of other complications, including diabetes, cardiovascular disease, glaucoma, and serious infection.[66][67][68]
Tocilizumab or methotrexate may be considered by a specialist in combination with the glucocorticoid taper in patients with GCA who relapse, have refractory disease, or who are at high risk of glucocorticoid toxicity.[35][36]
The interleukin-6 receptor inhibiting monoclonal antibody tocilizumab has been shown to be effective in patients with GCA, with one randomised controlled trial showing substantial reduction in the need for glucocorticoid therapy.[69][70][71]
A Cochrane review concluded that tocilizumab is an effective and safe glucocorticoid‐sparing therapy in patients with newly diagnosed and relapsing GCA.[72] Adverse effects of tocilizumab include hepatic injury (see below), serious infections and neutropenia, an alteration in lipid profiles, and bowel perforation.[73][74][75][76]
Guidelines state that methotrexate may be used as an alternative to tocilizumab, for example in those unable to use tocilizumab due to recurrent infections, history of gastrointestinal perforations, or diverticulitis.[35][36][77] However, in the opinion of our expert, methotrexate may be considered first line as a glucocorticoid-sparing option because it has been in clinical use for longer than tocilizumab and is less toxic.
More information: Tocilizumab and methotrexate
One randomised trial found that patients with active GCA who received tocilizumab with glucocorticoid taper had higher rates of sustained remission at 52 weeks and fewer relapses than patients who received glucocorticoid taper alone.[71] Overall adverse events were similar, but serious adverse events were less frequent among those receiving tocilizumab.
In an open-label follow-up, a substantial proportion of patients who were in clinical remission following treatment with tocilizumab for 52 weeks maintained drug-free remission during the 2 years after tocilizumab cessation. Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in the follow-up.[78] Systematic reviews also suggest that tocilizumab reduces relapse rates and glucocorticoid requirements.[79][80]
Tocilizumab is given in combination with a tapering course of a glucocorticoid, but its optimal usage in routine clinical practice and its optimal duration remain to be determined, and it is associated with significant cost.
In England and Wales, the National Institute of Health and Care Excellence states that tocilizumab, when used with a tapering course of glucocorticoids (and when used alone after glucocorticoids), is recommended as an option for treating GCA in adults, only if:[81]
They have relapsing or refractory disease
They have not already had tocilizumab
Tocilizumab is stopped after 1 year of uninterrupted treatment at most
The company provides it with the discount agreed in the patient access scheme.
Randomised controlled trials evaluating the efficacy of methotrexate in patients with GCA have yielded conflicting results.[82][83] However, evidence from one meta-analysis of individual patient data suggested that methotrexate may be effective at lowering the risk of first and second relapse and exposure to glucocorticoids.[84]
Drug safety information: Hepatic injury with tocilizumab
Cumulative analysis of safety data has identified cases of tocilizumab-related serious hepatic injury, including acute liver failure, hepatitis, and jaundice. Serious liver injury has been reported from 2 weeks to more than 5 years after starting treatment.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels should be measured before starting treatment with tocilizumab and monitored every 4 to 8 weeks for the first 6 months of treatment followed by every 12 weeks thereafter. Specialists should exercise caution when considering use of tocilizumab in patients with hepatic impairment, particularly in patients with ALT or AST higher than 1.5 times the upper limit of normal. Initiation of treatment is not recommended in patients with ALT or AST higher than 5 times the upper limit of normal.[85]
Do not routinely give antiplatelet agents or anticoagulants.[35][36] However, they may be considered on an individual basis for select patients with vascular ischaemic complications or who are at high risk of cardiovascular disease.[35] Follow national guidance on the secondary prevention of coronary and other atherosclerotic vascular diseases.
More information: Low-dose aspirin
Prevention of platelet aggregation with low-dose aspirin is potentially effective in preventing ischaemic complications of GCA. Retrospective chart reviews suggest that the risk of vision loss and stroke is lower, and the risk of bleeding complications was increased, in patients with GCA receiving aspirin.[35][36] However, other observational studies have failed to replicate these findings.[86][87] One meta-analysis of observational studies reported a marginal benefit when antiplatelet/anticoagulant therapy was used together with glucocorticoid therapy in patients with established GCA, without an associated increase in bleeding risk.[88]
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