K1-70, Teprotumumab, Rituximab

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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TEPROTUMUMAB:  Anti-IGF-IR antibody

Intravenous teprotumumab 8 injections every 3 weeks

10 mg/kg initial dose to 20 mg/kg

The 2017  NEJM study involved only 88 patients.  Patients with severe Graves orbitopathy were not examined.

SIDE EFFECTS:  Hyperglycemia

Muscle spasm, diarrhea

Thrombocyotopenia, anemia

Fatigue

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718164/

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The use of rituximab in Graves orbitopathy remains controversial.  Two 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

 

RITUXIMAB CONSENT                       Please initialize each blank.  **           

I understand that I have vision-threatening Graves Orbitopathy, and that the intravenous drug rituximab is being offered to me as an option / in addition,  to conventional steroids, surgery or radiation.   Rituximab is thought to work by depleting the number of the B-cells, cells of the immune system, which are important in promoting inflammation.  **            

I understand that rituximab is NOT covered by OHIP.  **             

I understand that rituximab for Graves Orbitopathy is at present off-label (company non-approved) use, although there are publications studying small numbers of Graves patients that describe the use of rituximab for vision-threatening Graves Orbitopathy.  **             

I understand that the choice to use intravenous rituximab is mine alone.  Usually 2 infusions of rituximab (500-1000 mg) are given 2 weeks apart.  Premedication with tylenol and gravol is required, and sometimes steroids.  **               

I understand that Dr. Ing is an eye doctor, and cannot manage the possible systemic complications associated with rituximab use.  The patient will have to go to the emergency room, their internist or family doctor, if any complications of treatment arise.  **                

The most common side effect of rituximab is a constellation of symptoms (fever, rigors, chills) that occur during administration of the first dose of drug. **                  

More than 80% of patients experience these side effects, and it is severe in 4-7 out of every 10,000 patients. The side effects appear only 40% of the time with the second dose of drug and decreases with subsequent doses.  Rarely anaphylaxis can occur with the 2nd dose.  **                  

Other common side effects related to rituximab are nausea, hives, fatigue, headache, itching, difficulty breathing due to bronchospasm, a sensation of swelling of the tongue or throat, runny nose, vomiting, decreased blood pressure, flushing, and pain at the site of the tumor.  **                     

Irregular heart rhythms and infection are two other rarely-occurring side effects that may be severe. The irregular heart rhythm usually begins soon after the administration of the drug, while infection may develop from 30 days to 11 months after the end of therapy.  **                    

Severe decreases in red or white blood cells and platelets may occur rarely with rituximab therapy.Generally, rituximab is avoided in the presence of active significant infections.  **                     

Nausea, vomiting, constipation, diarrhea and abdominal pain may occur.  **                    

Rituximab therapy is not recommended if there is an allergy to mice or rats since rituximab is made in mice or rats and may contain minute amounts of rat or mouse proteins that can lead to severe allergic reactions.  **                        

Some patients with severe immune deficiency run the risk of severe reactivation of previously quiescent infections, including progressive multifocal leukoencephalopathy (PML).  **                        

 

Patient name:                                                                          Date:                                           

Witness:                                                

 

After rituximab is administered FOR LYMPHOMA, (not Graves Orbitopathy) large numbers of tumor cells are immediately destroyed (lysed) and eliminated from the body. In 4-5 out of every 10,000 patients the products from the dead cells cannot be eliminated quickly enough and a syndrome called tumor lysis syndrome occurs. This is characterized by a rapid decline in kidney function and a sudden accumulation or decrease in minerals such as potassium, calcium and phosphate to dangerous levels. Tumor lysis syndrome occurs when the size of the tumor or the number of tumor cells circulating in the blood is large, usually within 12-24 hours after the first dose of rituximab. **                     
Insulin growth factor may promote orbital fibroblast activity in thyroid orbitopathy. Teprotumumab is an inhibitor of insulin growth factor.  It is a high potency, high specificity monoclonal antibody antagonist of human insulin growth factor and is being trialled in the U.S..