Recommendations

Key Recommendations

The goal of treatment is to improve symptoms and, more importantly, to prevent vision loss.[63] Glucocorticoids are the standard therapy, and patients typically respond promptly to treatment. The addition of tocilizumab, methotrexate, or abatacept may allow for a significantly shorter duration of glucocorticoid therapy.[34]​ The American College of Rheumatology/Vasculitis Foundation guideline has issued a conditional recommendation for the use of of oral glucocorticoids with tocilizumab over oral glucocorticoids alone.[34]

Glucocorticoids

If clinical suspicion is high, treatment with glucocorticoids should be started immediately while awaiting confirmation of diagnosis, including results of temporal artery biopsy and acute-phase reactants (erythrocyte sedimentation rate/C-reactive protein).[34][64]

Vision loss due to ischemic optic neuropathy (ION) from GCA is regarded as irreversible. Greater disease awareness and earlier use of glucocorticoids likely accounts for a decline in the incidence of ION due to GCA.[65] Even after several weeks of glucocorticoid therapy, temporal artery biopsy may still yield a diagnosis of arteritis.[35][36]

Oral prednisone should be started.[9][53]​ High-dose therapy is recommended to achieve rapid disease control in newly diagnosed patients.[34] Alternate-day dosing of glucocorticoids is not recommended.[34]

Recent or impending vision loss

More aggressive treatment may be indicated for patients who present with recent or impending vision loss. Newly diagnosed patients with threatened visual loss may benefit from an intravenous pulse-dose corticosteroid, but there is a risk of toxicity and the decision should be guided by the patient's clinical condition, values, and preferences.[34] These patients should receive pulse-dose methylprednisolone followed by the standard oral prednisone regimen.[34][63][66]​ This regimen may result in lower long-term glucocorticoid requirements. Patients who experience disease relapse while receiving moderate- to high-dose glucocorticoids may benefit from the addition of an immunosuppressive drug (e.g., tocilizumab, methotrexate, or abatacept) over increasing the dose of the glucocorticoid alone.[34]

Prednisone taper

The dosing and duration of oral glucocorticoid therapy can be variable depending on a patient's manifestations and comorbidities and whether the use of a corticosteroid-sparing agent was also initiated.[34] The dose of prednisone can be tapered (over several months) once remission has been achieved. When prednisone is used with tocilizumab, prednisone is typically tapered over 26 weeks.[67]​ During prednisone taper, patients should be evaluated regularly by clinical examination and inflammatory markers periodically checked. Patients with GCA frequently experience unpredictable disease relapses, requiring an increase in the glucocorticoid dose; however, isolated elevation of inflammatory markers in the absence of clinical symptoms should not automatically result in escalation of therapy.

Recent or impending vision loss

More aggressive treatment may be indicated for patients who present with recent or impending vision loss. Newly diagnosed patients with threatened visual loss may benefit from an intravenous pulse-dose corticosteroid, but there is a risk of toxicity and the decision should be guided by the patient's clinical condition, values, and preferences.[34] These patients should receive pulse-dose methylprednisolone followed by the standard oral prednisone regimen.[34][63][66]​ This regimen may result in lower long-term glucocorticoid requirements. Patients who experience disease relapse while receiving moderate- to high-dose glucocorticoids may benefit from the addition of an immunosuppressive drug (e.g., tocilizumab, methotrexate, or abatacept) over increasing the dose of the glucocorticoid alone.[34]

Management of glucocorticoid-induced adverse effects

The treatment of GCA is associated with significant toxicity; therefore, measures to prevent or treat glucocorticoid-related adverse effects are very important. Measures include preventing glucocorticoid-induced bone loss with optimized intake of dietary and supplemental calcium and vitamin D based on age-appropriate national recommended dietary allowances.[68] Patients ages ≥40 years receiving long-term glucocorticoids and deemed to be at high risk of fracture should receive an oral bisphosphonate. Other agents including intravenous bisphosphonates, parathyroid hormone/parathyroid hormone analogs (e.g., teriparatide, abaloparatide), or denosumab are also options. Selection of an agent should be based on patient and physician preferences.[68] Fracture assessment (including bone mineral density testing) is recommended within 6 months of starting glucocorticoid therapy for adults and every 1-2 years thereafter while continuing glucocorticoid therapy.[68]​ Long-term treatment with high-dose corticosteroids carries a high risk of other complications, including diabetes, cardiovascular disease, glaucoma, and serious infection.[69][70][71]​​​

Tocilizumab

The anti-interleukin-6 receptor antibody tocilizumab has been shown to be effective in patients with GCA,[72][73] with substantial therapeutic benefits for patients with newly diagnosed or relapsing GCA.[67][74]​​

Systematic reviews suggest that tocilizumab reduces relapse rates and glucocorticoid requirements.[75][76]

One randomized 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.[67] Overall adverse events were similar, but serious adverse events were less frequent among those receiving tocilizumab.

Oral glucocorticoids with tocilizumab may be preferable over oral glucocorticoids alone, but the decision to use tocilizumab should be made based on the physician's experience and the patient's clinical condition, values, and preferences.[34] This combined therapy may particularly benefit patients with new, persistent, or worsening extracranial symptoms (e.g., limb claudication) or signs of extracranial large vessel involvement (e.g., limb claudication) or signs (e.g., imaging findings) attributable to GCA.[34]

Tocilizumab is given in combination with a tapering course of a glucocorticoid, but its optimal usage in routine clinical practice and its optimal duration remains to be determined. Lack of long-term follow-up data on tocilizumab and significant cost may limit its use.[34]

Adverse effects

Cumulative analysis of safety data has identified eight cases of tocilizumab-related serious hepatic injury, including acute liver failure, hepatitis, and jaundice.[77] Serious liver injury has been reported from 2 weeks to more than 5 years after starting treatment. Use tocilizumab with caution in patients with hepatic impairment. Other adverse events related to tocilizumab include serious infections and neutropenia, an alteration in lipid profiles, and bowel perforation.[78][79][80][81]​​​

Methotrexate

Randomized 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] Methotrexate may be an alternative to tocilizumab in patients unable to use tocilizumab (e.g., due to recurrent infections, history of gastrointestinal perforations, or diverticulitis).[34]

Abatacept

In patients for whom tocilizumab and methotrexate are not effective or tolerated, the American College of Rheumatology recommends considering abatacept in addition to glucocorticoids.[34] However, this recommendation is supported by one small randomized double-blind trial of 49 patients, in whom the addition of abatacept to a standardized prednisone taper was shown to be of benefit.[85] Specifically, the relapse-free survival rate at 12 months was 48% for those receiving abatacept and 31% for those receiving placebo (P=0.049).

Aspirin

Low-dose aspirin treatment should be considered on an individual basis. It may benefit patients with GCA who have critical or flow-limiting involvement of the vertebral or carotid arteries.[34]

Prevention of platelet aggregation with low-dose aspirin is potentially effective in preventing ischemic complications of GCA. Retrospective chart reviews suggest that the risk of vision loss and stroke is lower, and the risk of bleeding complications not increased, in patients with GCA receiving aspirin.[86][87] However, other observational studies have failed to replicate these findings.[88][89] One meta-analysis of observational studies reported a marginal benefit when antiplatelet/anticoagulant therapy was used together with corticosteroid therapy in patients with established GCA, without an associated increase in bleeding risk.[90]

European guidelines recommend against routine antiplatelet or anticoagulant therapy for the treatment of GCA.[91] However, these agents may be considered on an individual basis for select patients with vascular ischemic complications or who are at high risk of cardiovascular disease.[91]

Prospective clinical trials are required.[92]

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