Medication Summary
The goals of therapy in Takayasu arteritis are to reduce inflammation and suppress autoimmune disease. To treat the active disease, corticosteroids are used and gradually tapered. Cytotoxic agents such methotrexate, azathioprine, and cyclophosphamide are the main therapeutic agents when the response to steroids is unsatisfactory. As previously mentioned, anti–tumor necrosis factor (anti-TNF) agents have shown encouraging results in a small number of patients with relapsing Takayasu arteritis. [48]
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.
Prednisone
The immunosuppressant prednisone is a first-line therapy administered for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity and CD4 counts.
Antineoplastics, Other
Class Summary
Cyclophosphamide or methotrexate—either in combination with prednisone or alone—can be used to suppress active disease in patients who are not responding to prednisone.
Cyclophosphamide
Cyclophosphamide may be added to steroid therapy if the patient has shown minimal response to steroid treatment or has been on a steroid for a prolonged period of time. Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of deoxyribonucleic acid (DNA), which may interfere with the growth of normal and neoplastic cells.
Methotrexate (Trexall, Rheumatrex)
Methotrexate may be added to treatment if steroid therapy has not been effective or if the patient has been on steroid treatment for a prolonged period of time. Methotrexate has an unknown mechanism of action in the treatment of inflammatory reactions; the drug may affect immune function. Methotrexate ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response.
Effects can be observed as early as 3-6 weeks following methotrexate's administration. Methotrexate is used as second- or third-line drug to suppress active disease.
Immunosuppressants
Class Summary
These agents inhibit key factors that mediate immune reactions. [53]
Azathioprine (Imuran, Azasan)
Azathioprine may be added to treatment if there has been no response to steroid therapy or if the patient has been on steroid treatment for a long period of time. Azathioprine antagonizes purine metabolism and inhibits the synthesis of DNA, ribonucleic acid (RNA), and proteins. It may decrease the proliferation of immune cells, which results in lower autoimmune activity.
Mycophenolate (CellCept, Myfortic)
Mycophenolate inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Mycophenolate inhibits antibody production.
Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (CellCept), is a prodrug that, once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (Myfortic), is an enteric-coated product that delivers the active moiety.
Tacrolimus (Prograf)
Tacrolimus suppresses humoral (T-lymphocyte) immunity.
Infliximab (Remicade)
Infliximab may be added to treatment if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Infliximab is a chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-α and inhibits its binding to the TNF-α receptor. It reduces the infiltration of inflammatory cells and TNF-α production in inflamed areas.
Tocilizumab (Actemra)
Tocilizumab is an IL-6 receptor inhibitor. IL-6 inhibition results in a decreased C-reactive protein level to within the normal range, decreased values in other pharmacodynamic parameters (eg, rheumatoid factor, erythrocyte sedimentation rate, amyloid A), and an increased hemoglobin value.
Rituximab (Rituxan)
Rituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of B-lymphocytes.
DMARDs, TNF Inhibitors
Class Summary
These agents play an important role in modulating the inflammatory process.
Etanercept (Enbrel)
Etanercept may be added to treatment if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Etanercept is a soluble p75 TNF receptor fusion protein (sTNFR-Ig). It inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses.
Calcium Channel Blockers
Class Summary
These drugs can be used to treat hypertension associated with arteritis. On occasion, combinations are required. Therapy can be individualized.
Nifedipine (Procardia)
Nifedipine is one of the more common channel blockers used for hypertension associated with arteritis.
Antiplatelet Agents, Hematologic
Class Summary
These drugs help to prevent cerebrovascular accidents and improve renal and systemic function.
Ticlopidine hydrochloride
Ticlopidine hydrochloride interferes with platelet membrane function by inhibiting adenosine diphosphate (ADP) ̶ induced platelet-fibrinogen binding and subsequent platelet-platelet interaction. It is used as a second-line antiplatelet therapy for patients who are intolerant to aspirin therapy or in whom such therapy fails.
Clopidogrel (Plavix)
Clopidogrel is a thienopyridine derivative chemically related to ticlopidine that inhibits platelet aggregation; it selectively inhibits ADP binding to its platelet receptor and subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
Aspirin and extended-release dipyridamole (Aggrenox)
This drug combination has antithrombotic action. Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. It may be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.
Dipyridamole is a platelet adhesion inhibitor that possibly inhibits red blood cell uptake of adenosine, itself an inhibitor of platelet reactivity. In addition, dipyridamole may inhibit phosphodiesterase activity leading to increased cyclic-3', 5'-adenosine monophosphate within platelets and formation of the potent platelet activator thromboxane A2.
Anticoagulants, Hematologic
Class Summary
In patients with renal failure due to crescentic glomerulonephritis and nephrotic syndrome, low-dose heparin followed by oral anticoagulation leads to improved renal and systemic function. It probably reduces the destructive effects of fibrin thrombi in the small vessels of the kidney.
Warfarin (Coumadin, Jantoven)
Warfarin interferes with hepatic synthesis of vitamin K ̶ dependent coagulation factors. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.
Tailor the dose to maintain an international normalized ratio (INR) in the range of 2-3.
Heparin
Heparin augments the activity of antithrombin III. It does not actively lyse, but it is able to block further thrombogenesis. Heparin prevents reaccumulation of a clot after a spontaneous fibrinolysis.
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Takayasu arteritis. Complete occlusion of the left common carotid artery in a 48-year-old woman with Takayasu disease. Also note narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Aortogram of a 15-year-old girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery. Image courtesy of Christine Hom, MD.
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Takayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.
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Takayasu arteritis. Coronal MRI of abdomen of 15-year-old girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys. Image courtesy of Christine Hom, MD.
