CLINICAL ACTIVITY SCORE >=3/7 suggests active disease
Spontaneous pain behind eye
Pain on trying to look up or down
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
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 which is considered if glucocorticoids (steroids) or radiation are not effective. Surgery is often still required.
Possible administration regimen: 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 thyroid-associated orbitopathy. **
I understand that tocilizumab for TAB 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 publications studying small numbers of TAO patients that describe favourable results with the use of tocilizumab for vision-threatening thyroid associated Orbitopathy. **
I understand that the choice to use tocilzumab is mine alone. **
I understand tocilizumab has many possible SIDE EFFECTS: Tocilizumab can lower the ability of your immune system to fight infections. All patients should be tested for tuberculosis before starting on tocilizumab, although these types of infections have not been frequently seen. Allergic reactions to IV tocilizumab infusions can occur, which can include symptoms such as fever and chills, but these are rare. Tocilizumab has been associated with increased cholesterol levels in some patients, and should be periodically monitored. If your cholesterol level becomes too high, it is possible you may need to start taking a medication to lower it. A rare complication seen with tocilizumab use in clinical trials
was bowel perforation, or a hole in the bowel wall. 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. if you think you are having any side effects, especially abdominal pain, bloody bowel movements, or allergic reactions. 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:
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
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.