Giant Cell Arteritis (Temporal Arteritis) Medication

Updated: Sep 10, 2020
  • Author: Mythili Seetharaman, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication

Medication Summary

Oral corticosteroids are the mainstay of treatment for giant cell arteritis (GCA). Intravenous (IV) steroids may be administered if visual deficit is established or if the patient requires admission for other reasons.

However, no consensus exists regarding a standard initial dose or maintenance dosing schedules for corticosteroids. Authorities do agree that the initiation of steroid therapy should not be delayed while awaiting temporal artery biopsy, because biopsy can still confirm the diagnosis, especially during the first week of steroid therapy, and prompt therapy can help the patient avoid serious sequelae.

The US Food and Drug Administration (FDA) approved tocilizumab, the first drug specifically approved for GCA, in May 2017. It is a humanized monoclonal anti–interleukin-6 receptor antibody. Approval was based on the GiACTA trial,in which tocilizumab was added to standardized prednisone regimens. [153]

Other possible therapeutic drug options include cyclophosphamide, cyclosporine, dapsone, rituximab (anti-CD20 monoclonal antibody), and abatacept (a recombinant fusion protein that modulates CD28-mediated T cell co-stimulation). [21] Generally, none of these agents is routinely recommended.

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Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli and inhibit the synthesis of tumor necrosis factor (TNF)-alpha, interleukin-2 (IL-2), IL-6, and interferon (IFN)-gamma. In addition, glucocorticoids modulate serum and leukocyte-bound levels of cell adhesion molecules.

Corticosteroid therapy for GCA is started at high doses with gradual tapering, using clinical manifestations and the erythrocyte sedimentation rate (ESR) to gauge disease activity. An initial dose of 40-60 mg/d of prednisone (or equivalent) in a single or divided dose is adequate in the vast majority of cases. This dose is usually given for 2-4 weeks until all reversible signs and symptoms have resolved and levels of acute-phase reactants are back to normal. The dose is then gradually reduced every 1-2 weeks by a maximum of 10% of the total daily dose.

Most patients are treated for 1-2 years, but some with a prolonged or relapsing course may require low doses of steroids for several years. Clinical flares usually occur when the prednisone is reduced to 5-10 mg/d.

Prednisone (Rayos)

The drug of choice in GCA, prednisone is an oral corticosteroid that must be metabolized in the liver to its active metabolite, prednisolone. Prednisone decreases inflammation by suppressing migration of polymorphonuclear neutrophils (PMNs) and reversing increased capillary permeability.

Typical patients require prednisone for 1-2 y with daily initial doses of 40-60 mg. In acute neurologic syndrome or rapidly worsening neurologic status—whether visual loss, mononeuritis multiplex, or acute encephalopathy—treatment may begin with IV pulses over several days.

A patient with GCA who has a relapse may require only a modest dose increment to control flare in symptoms. Following initiation of treatment, ESR may be expected to drop within days and become normal in 1-2 wk. All neurologic deficits can improve, but irreversible end-organ infarction may preclude clinically significant gains in some patients.

Neurovascular complications may occur during initial tapering of corticosteroid dosage (often around 1 mo after beginning treatment), underscoring the need for ESR monitoring and the importance of small steroid decrements. The doses described below are suggested for general consideration. Tailor dosing regimens to medical circumstances confronting patient.

Prednisolone (Flo-Pred, Prelone, Millipred, Orapred)

Prednisolone decreases inflammation by suppressing migration of PMNs and reducing capillary permeability.

Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol, A-Methapred)

Methylprednisolone decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability. This agent is slightly more potent than prednisone; 4 mg of methylprednisolone is equivalent to 5 mg of prednisone.

Dexamethasone (Baycadron)

Dexamethasone is a glucocorticoid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.

Dexamethasone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose-dependent or duration-dependent.

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Interleukin Inhibitors

Class Summary

Adventitial macrophages produce interleukin-6 (IL-6), augmenting the inflammatory response. This results in inflammation with local vascular damage and intimal hyperplasia, leading to stenosis and occlusion. IL-6 antagonists may decrease inflammation from this pathway.

Tocilizumab (Actemra)

Interleukin-6 receptor antagonist. Inhibits IL-6-mediated signaling that results in proinflammatory cytokines. It is indicated for treatment of GCA in adults.

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Immunosuppressant Agents

Class Summary

These agents inhibit key factors of the immune system. They may have anti-inflammatory properties in GCA and result in steroid sparing in relatively resistant cases.

Azathioprine (Azasan, Imuran)

Azathioprine is an imidazolyl derivative of 6-mercaptopurine, and many of its biological effects are similar to those of the parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and liver. No azathioprine or mercaptopurine is detectable in urine 8 h after the agent is taken.

Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting the synthesis of DNA, RNA, and proteins. The mechanism by which azathioprine affects autoimmune diseases is unknown. Azathioprine works primarily on T cells; it suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity test results are suppressed to a greater degree than antibody responses.

This agent is reserved for patients experiencing steroid failure or unacceptable adverse effects from prolonged steroid use; it can be used for its steroid-sparing effects to allow lowering of the steroid dose. It is available in tablet form for oral administration and in 100-mg vials for intravenous injection.

Cyclosporine (Neoral, Sandimmune, Gengraf)

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease for a variety of organs. For children and adults, base dosing on ideal body weight. Available dosage strengths include 25 mg, 50 mg, and 100 mg/mL.

Methotrexate (Trexall, Rheumatrex)

Methotrexate ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Its

mechanism of action in treatment of inflammatory reactions is unknown; this agent may affect immune function. Adjust dose gradually to attain satisfactory response.

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Antiplatelet Agents

Class Summary

Low-dose aspirin decreases the rates of visual loss and strokes in patients with giant cell arteritis.

Aspirin (Bayer Buffered Aspirin, Bayer Aspirin, Halfprin, St. Joseph Adult Aspirin, Ascriptin Regular Strength)

Aspirin is an odorless white powdery substance available in 81 mg, 325 mg, and 500 mg strengths for oral use. When exposed to moisture, aspirin hydrolyzes into salicylic acid and acetic acids. Aspirin is a stronger inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. Acetyl group is responsible for inactivation of cyclooxygenase via acetylation. Aspirin is hydrolyzed rapidly in plasma, and elimination follows zero-order pharmacokinetics.

Aspirin irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to prostaglandin I2 (PGI2, is a potent vasodilator and inhibitor of platelet activation), and thromboxane A2 (a potent vasoconstrictor and platelet aggregator). Platelet inhibition lasts for the life of the cell (approximately 10 d).

Aspirin may be used in a low dose to inhibit platelet aggregation and improve the complications of venous stasis and thrombosis. It reduces the likelihood of myocardial infarction and the risk of stroke.

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