CLINICAL ACTIVITY SCORE >=3/7 suggests active disease
Spontaneous pain behind eye
Pain on trying to look up or down
Red eyelids
Swollen eyelids
Red conjunctiva
Swollen conjunctiva
Inflamed caruncle / plica
TEPROTUMUMAB: Anti-Insulin Growth Factor -IR inhibitor (Tepezza is NOT available in Canada)
Insulin growth factor may promote orbital fibroblast activity in thyroid associated orbitopathy. Teprotumumab is a high potency, high specificity monoclonal antibody antagonist of human insulin growth factor and is available in the U.S. but not Canada as of 2020.
Teprotumumab is given intravenously 8 injections every 3 weeks.
(8 infusions of teprotumumab (10 mg/kg for the first infusion followed by 20 mg/kg for the remaining 7 infusions))
The 2017 NEJM study involved only 83 (88) patients.
Intravenous q 3 weeks for 8 doses (i.e. 24 weeks)
First dose: 10 mg/kg
Subsequent doses: 20 mg/kg
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TOCILIZUMAB (ACTEMRA)
Tocilizumab blocks the inflammatory protein interleukin-6 (IL-6) which can decrease orbital swelling from arthritis and inflammation. Tocilizumab is commonly used for rheumatoid arthritis and giant cell arteritis.
Tocilizumab is administered intravenously or subcutaneously. Tocilizumab is an OFF-LABEL (the medication is being used in a manner not specified in Health Canada or the U.S. FDA’s approved packaging label, or insert) treatment for severe thyroid-associated orbitopathy or orbital inflammatory disease which is considered especially when glucocorticoids (steroids) or radiation are not effective. Surgery may still be required.
The subcutaneous injection regimen is: 162 mg/mL sc weekly (8 injections). Silkiss & Weiss, 2021, CJO.
TOCILIZUMAB PATIENT CONSENT Please initialize each blank. **
I understand that I have severe / vision-threatening thyroid-associated orbitopathy (TAO, Graves Orbitopathy, thyroid eye disease), and that tocilizumab is being offered to me as an option / in addition to more conventional steroid treatment, surgery or radiation. Tocilizumab decreases interleukin-6, and may help decrease orbital inflammation. **
I understand that tociluzmab is NOT covered by OHIP for orbital inflammations and thyroid-associated orbitopathy. **
I understand that tocilizumab for orbital inflammations is at present off-label (not approved by the drug company, Health Canada or the U.S. FDA for thyroid-associated orbitopathy) use, although there are numerous publications with small numbers of patients that describe favourable results with the use of tocilizumab for thyroid associated orbitopathy and other orbital inflammations. **
I understand that the choice to use tocilzumab is mine alone. **
I understand tocilizumab has possible SIDE EFFECTS:
The most common side effects are: upper respiratory tract infections (common cold, sinus infections), headache, increased blood pressure (hypertension), redness around the injection site
Tocilizumab can lower the ability of your immune system to fight infections. Patients with tuberculosis and hepatitis should not get tocilizmuab. **_____
Allergic reactions to IV tocilizumab infusions can occur, which can include symptoms such as fever and chills, swelling of the lips or tongue and shortness of breath, but these are rare. **______
Some patients on tocilizumab may develop very serious liver problems. If you develop yellow skin, right sided stomach pain, or gastrointestinal upset you should stop tocilizumab and tell your family doctor ** _______
A rare complication was bowel perforation, or a hole in the bowel wall (patients were often on NSAID, methotrexate or steroids). If you have a history or diverticulitis or develop abdominal pain or bloody bowel movements while taking tocilizumab, you should notify your family doctor immediately. ** ______
Rarely patients on tocilizumab may develop cancer or multiple sclerosis. ** _____
Some patients on tocilizumab may develop high cholesterol, low white blood cell count, low platelet count, and high liver function tests. Your family doctor should help monitor these blood tests if you are using tocilizmuab. **______
If you become pregnant, are planning pregnancy, or if you are breastfeeding be sure to tell your doctor. Inform your surgeon if you are planning on having surgery, or if you plan on getting any live vaccinations; these include the shingles vaccine (Zostavax), the nasal spray flu vaccine, and others such as the measles, mumps, rubella, and yellow fever vaccines. **______
I understand that Dr. Ing is an eye doctor, and cannot manage the possible systemic complications associated with tocilizumab use. The patient will have to go to the emergency room, their internist or family doctor, if any complications of treatment arise. **
I understand that toclizumab may NOT be an option in patients wtih prior tuberculosis or other infections, with certain cancers, liver disease (hepatitis B/C), diminished white blood count or platelets, diverticulitis, certain heart problems. **___________
Patient name: Date:
Witness:
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K1-70: a human monoclonal autoantibody to the TSH receptor
TSH receptor pathway specifically with monoclonal antibodies, the risks and side effects are expected to be far fewer than Teprotumumab
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RITUXIMAB can have severe side effects, and the use of rituximab in Graves orbitopathy remains controversial. Two older randomized control studies have shown conflicting results.
Salvi http://www.ncbi.nlm.nih.gov/pubmed/25494967
Stan http://www.ncbi.nlm.nih.gov/pubmed/25343233