Giant Cell Arteritis (Temporal Arteritis) Treatment & Management

Updated: May 23, 2017
  • Author: Mythili Seetharaman, MD; Chief Editor: Herbert S Diamond, MD  more...
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Treatment

Approach Considerations

The universally accepted treatment of giant cell arteritis (GCA) is high-dose corticosteroid therapy. [51, 20, 7, 131, 132] The major justification for the use of corticosteroids is the impending danger of blindness in untreated patients. Patients who present with visual symptoms have a 22-fold increased chance of visual improvement if therapy is started within the first day. Damage may be irreversible if treatment is delayed beyond 48 hours.

Few studies exist regarding dosing protocols for corticosteroids in GCA. It is generally agreed that most patients with suspected GCA should be started on oral prednisone 40-60 mg/day, with a temporal artery biopsy performed within 1 week. [100] Prednisone doses of 80-100 mg/day have been suggested for patients with visual or neurologic symptoms of GCA. [133] Follow-up care within 72 hours after starting therapy should be arranged.

Alternatively, patients with acute visual changes from GCA can be started on intravenous (IV) methylprednisolone at doses of 250-1,000 mg daily for 3 days. In addition, limited data suggest that initial high-dose IV corticosteroid treatment (eg, methylprednisolone, 15 mg/kg of ideal body weight/day) may reduce remission rates. [134, 135] However, further study is warranted before this is routinely practiced.

Improvement of systemic symptoms (eg, headache, lethargy) typically occurs within 72 hours of initiation of therapy. The elevation in erythrocyte sedimentation rate (ESR) and ischemic manifestations (eg, temporal headache, jaw claudication) diminish in several days. The ESR often drops even in patients with a normal baseline reading.

Patients with multi-infarct dementia from GCA should not expect immediate cognitive recovery; however, longitudinal follow-up should show no further deterioration and may show modest improvement. Even with prompt treatment, visual loss may be permanent.

High-dose steroid therapy should be maintained only long enough for symptoms to resolve. Steroids should then be tapered slowly to the lowest dose required to suppress symptoms. Both clinical signs and sequential measurements of the ESR (or C-reactive protein level) assist in monitoring the patient's response. Patients with visual involvement usually require slower tapering of corticosteroids.

British guidelines recommend the following schedule for tapering of standard-regimen corticosteroids [51] :

  • Continue prednisolone, 40-60 mg (not <0.75 mg/kg) for 4 weeks (or until symptoms and laboratory abnormalities resolve), then
  • Reduce dose by 10 mg every 2 weeks to 20 mg, then
  • Reduce dose by 2.5 mg every 2-4 weeks to 10 mg, then
  • Reduce dose by 1 mg every 1-2 months, provided no relapse occurs

The guidelines recommend that patients on steroid therapy receive prophylactic treatment with the following medications [51] :

  • Low-dose aspirin, 81 mg per day – To decrease cranial ischemic complications
  • Proton pump inhibitor – For gastrointestinal protection
  • Bisphosphonate, calcium, and vitamin D – For bone protection

Sequential ESR determination may assist in determining the success of corticosteroid therapy. Once the signs of clinical inflammation are suppressed and the ESR is maintained at a low level, corticosteroids may be tapered In almost all patients, the steroid dosage can be significantly decreased; however, the inflammatory process may ebb and flow, and temporary dose increases may be needed to control disease flares. Relapse occurs in 25-60% of cases.

The dose of prednisone should be increased only if clinical manifestations recur, and not simply on the basis of an elevation of the ESR. An elevated ESR without accompanying symptoms or signs of GCA could be related to an infection.

No absolute guidelines exist as to the length of treatment with corticosteroids for GCA. [100] It may be reasonable to maintain the patient on treatment for 2 years to lessen the chances for relapses. Even then, relapses have been reported. [136] Some patients may need treatment for as long as 5 years. Because the incidence of new visual damage appears to decrease with disease duration, consider a repeat temporal artery biopsy before restarting corticosteroids in patients who relapse after 18-24 months.

Long-term corticosteroid therapy has frequent and potentially serious consequences, including diabetes mellitus, vertebral compression fractures, steroid myopathy, steroid psychosis, and immunosuppression-related infections. [137] Indeed, the cumulative morbidity associated with long-term therapy often exceeds that of the underlying disease.

Interleukin-6 (IL-6) plays a role in the inflammation of GCA (see Pathophysiology). In phase 2 studies, treatment of GCA with the IL-6 receptor blocker tocilizumab resulted in faster achievement of remission, with significant reduction in corticosteroid doses, and prolonged maintenance of remission. [138, 139] In May 2017, the US Food and Drug Administration (FDA) expanded the indications for use of tocilizumabe for use in GCA. Tocilizumab had previously been approved for use in rheumatoid arthritis. [140]

Alternative immunosuppressant agents (eg, cyclosporine, azathioprine, methotrexate) may be started later in the course of treatment. They can be useful as steroid-sparing agents in patients who require prolonged treatment with high doses of steroids (more than 5-10 mg/d) and those who experience significant steroid-related complications.

Most patients with GCA can be treated on an outpatient basis. Hospital admission may be indicated for patients with particularly severe symptoms or those unable to provide self-care at home. After resolution of acute GCA, patients require regular followup to monitor for disease recurrence, steroid complications during steroid therapy, and long-term complications such as aortic aneurysm.

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Alternatives to Corticosteroids

Tocilizumab

Tocilizumab (Actemra) was approved by the FDA in May 2017 for giant cell arteritis (GCA). [140] Approval was based on the phase 3 GiACTA trial (n=251), in which subcutaneous tocilizumab or placebo was added to standardized prednisone regimens. [139]

The primary efficacy endpoint was the proportion of patients achieving sustained remission from week 12 through week 52. Sustained remission (resolution of GCA symptoms, normalization of inflammatory laboratory test results, and tapering of prednisone) occurred in a greater proportion of patients receiving tocilizumab compared with those receiving placebo (P ≤0.0002). The cumulative prednisone dose in patients treated with tocilizumab was less than half of that in patients who received placebo. [139]

In a phase 2 trial in 30 patients with GCA (new onset in 23, relapsing in seven) who were randomized to receive steroids plus either tocilizumab or placebo, 85% of patients given tocilizumab reached complete remission by week 12, compared with 40% of patients given placebo. By week 52, 85% of patients in the tocilizumab group achieved relapse-free survival versus 20% in the placebo group. Due to earlier discontinuation of steroids, the cumulative prednisolone dose after 52 weeks was 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group. [138]

In an open-label study, treatment with  tocilizumab led to rapid and maintained improvement in 19 of 22 patients whose GCA was refractory to corticosteroid treatment, or who had experienced unacceptable corticosteroid side effects. However, serious infection-related complications--including a fatal stroke associated with infective endocarditis--occurred in three patients. [141] Tocilizumab carries a boxed warning for serious infections. [140]

Tumor necrosis factor inhibitors

Tumor necrosis factor (TNF) inhibitors (eg, infliximab, etanercept) are being evaluated in clinical trials for the treatment of GCA. A randomized controlled trial showed that adding infliximab to steroids provided no measurable benefit in the management of newly diagnosed GCA. [142]

A double-blind, placebo-controlled trial of etanercept in steroid-refractory GCA yielded mixed results. The study included 17 patients who required a stable dose of prednisone of 10 mg/d to maintain clinical remission and had at least one steroid-related adverse effect. After 12 months, more of the patients in the etanercept group had successfully discontinued prednisone (50% versus 22.2% of placebo patients), but the difference was not significant. No difference was noted in the number and type of adverse events. [143]

However, patients in the etanercept group did have a significantly lower cumulative dose of accumulated prednisone during the first year of treatment (p = 0.03). The researchers noted that a larger trial with longer follow-up is needed to determine the role of etanercept in GCA therapy. [143]

Other immunosuppressants

Trials of other immunosuppressant agents, including cyclophosphamide, azathioprine, methotrexate, and dapsone, have been attempted for their steroid-sparing effects. Steroid dosages have been lowered successfully but inconsistently in some patients on each of these drugs. Toxicity can be a significant problem, particularly with dapsone and cyclophosphamide. [144]

Limited experience suggests that cyclophosphamide may be the most consistently effective immunosuppressant. It may permit more rapid steroid tapering when instituted after a relapse. Cyclophosphamide may be administered in monthly pulses. [122]

Azathioprine, in an average dosage of 1.5-2.7 mg/kg/day, reduced steroid requirements in a double-blind, placebo-controlled study that included 31 patients with GCA, polymyalgia rheumatic, or both. However, the advantage of azathioprine over placebo did not reach statistical significance until 1 year. [145]

Methotrexate has been used as a steroid-sparing agent, in doses of 15-25 mg/wk. However, evidence regarding its efficacy remains inconclusive. [146, 147, 148, 149]

In a formal meta-analysis, adjunctive methotrexate, 7.5-15 mg/wk, reduced the risk of a first relapse by 35% and of a second relapse by 51%. In addition, methotrexate reduced the cumulative exposure to steroids. However, the superiority of the treatment effect of methotrexate over placebo fully appeared only after a latency period of 24-36 weeks, and no between-group difference was noted in the occurrence of adverse events. [147]

Further trials

A number of clinical trials of GCA treatment are either actively recruiting or are active but not yet recruiting. For a complete list, see these List Results from ClinicalTrials.gov.

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Diet and Activity

Patients with GCA who are on steroid therapy should be monitored carefully for the steroid-related complications of diabetes mellitus, hypertension, peripheral edema, and weight gain. Management of dietary sugar, salt, and caloric intake may help to prevent such complications.

No activity restrictions are necessary in a patient with GCA who is asymptomatic on adequate therapy. If a patient has ischemic eye or brain symptoms, then bedrest in a supine position may be desirable before or when first beginning steroid therapy. Some patients may have orthostatically sensitive amaurosis fugax, but this is rare.

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Consultations

Immediate consultation with a rheumatologist is suggested when initiating high-dose steroid therapy for presumed GCA prior to performance of a temporal artery biopsy (TAB). Therapy should not be delayed if consultation is not available immediately, however.

Rheumatologic consultation also is indicated to consider the need for steroid therapy when biopsy results are negative, but the clinical presentation strongly suggests GCA. The occasional patient with GCA who does not respond adequately to steroid therapy requires a referral for reconsideration of the diagnosis and for other forms of immunosuppressive therapy.

Surgical consultation is necessary for TAB. Depending on the institution, this procedure can be performed by a neurosurgeon, plastic surgeon, ophthalmologist, or general surgeon.

It is imperative that the treating physician be familiar and confident with the laboratory that is evaluating the TAB specimen, since this is the criterion standard for GCA diagnosis. A myriad of laboratory errors (eg, specimen handling, fixation, sectioning) can, if they occur, result in a misdiagnosis (most often a false-negative result).

An ophthalmologist should be consulted for a complete, dilated ocular examination to rule out other causes of vision loss, particularly when the diagnosis is uncertain. Consultation with a neurologist is helpful for excluding other causes of headache.

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Long-Term Monitoring

Because giant cell arteritis (GCA) is a potentially blinding and lethal disease, regular follow-up care after a successful initial management of the acute process is considered a standard of care. Routine follow-up should include asking about symptoms of upper extremity claudication or ischemia, listening for bruits, and taking blood pressure in both arms. Ongoing monitoring of symptoms and the erythrocyte sedimentation rate (ESR) is mandatory.

The ESR often normalizes within days of instituting steroid therapy. With tapering of steroid doses, ischemic complications may occur at any time but tend to occur a median of 1 month after beginning therapy.

British guidelines recommend that patients with GCA have follow-up visits at weeks 1, 3, and 6 and then months 3, 6, 9, and 12 in the first year after diagnosis, with extra unscheduled visits as necessary if relapse or adverse events occur. [51] The typical patient with GCA remains on steroid therapy for roughly 2 years. Followup is recommended until 1 year after discontinuation of therapy.

During corticosteroid therapy, monitoring for complications of long-term use of these drugs is indicated. Patients should be screened for diabetes, hypertension, and cataracts.

Given the high risk of corticosteroid-induced osteoporosis, patients should have baseline bone densitometry at the start of therapy. All patients on corticosteroids need adequate calcium and vitamin D for protection against osteoporosis (1500 mg of calcium and 800 IU of vitamin D3 daily).

American College of Rheumatology guidelines provide an algorithm for determining whether a patient receiving corticosteroids is at low, medium, or high risk for osteoporosis. The guidelines also offer recommendations for treatment—including, where appropriate, pharmacologic treatment with alendronate, risedronate, zoledronic acid, or teriparatide, with the choice of agent determined partly by risk level. [150]

Vaccination against influenza and pneumococcal disease is of heightened importance, because of relative immunosuppression from steroids. Long-term high-dose steroid therapy increases risk for peptic ulcer disease, particularly in patients older than 65 years, so prophylaxis with histamine-2 blockers, proton pump inhibitors, or antacids is justified, especially in patients who are also taking nonsteroidal anti-inflammatory drugs. [151]

Retrospective but impressive data from Nesher and colleagues support the use of low-dose aspirin (81 mg) in patients with GCA for prevention of visual loss and stroke. [152] This therapy should be initiated in every patient diagnosed with GCA who does not have contraindications to its use.

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