Sunday, 3 November 2013

Thyroid disease with Alemtuzumab

Are you prepared to trade in your MS for thyroid disease? #MSBlog #MSResearch

"Alemtuzumab is the most effective DMT to be licensed so far and it has superior efficacy to interferon-beta in treating RRMS. It works by rebooting your immune system. When the immune system reconstitutes itself the part of it that triggers MS seems to be controlled. Exactly how this occurs is not clear at present, but may relate to the function of the so called regulatory cells of the immune system."

"The majority of MSers treated with alemtuzumab go into long-term remission without any evidence of MS disease activity after just 2 annual cycles of treatment. The most serious adverse events is the emergence of autoimmune diseases approximately 18 months after the last course. The commonest autoimmune disease is thyroid disease. The study below describes this problem in the 334 MSers participating in the phase 2 programme; 34% of alemtuzumab and 6.5% of interferon-treated MSers developed thyroid disease. Is this high? Yes it is high and if you choose to be treated with alemtuzumab you need to be prepared to be monitored for the emergence of this complication with 3-monthly thyroid function tests for 4 years after your last course of treatment. Thyroid disease is the one autoimmune disease  that is relatively easy to treat. The exception being autoimmune Graves eye disease that can occur in parallel with the thyroid gland disease. The eye disease or orbitopathy is a autoimmune disease in its own right with inflammation in the soft tissue surrounding the eye. This cause the eyeball to protrude, so called proptosis, and may affect the movement of the eye causing double vision. I have had one MSer with this complication, which was difficult to treat."

"Alemtuzumab is not for the faint-hearted; you need to highly motivated and understand the implications of the treatment. Despite this I think it will be a game-changer, simply because so many MSers treated with alemtuzumab, particularly early in the course of their disease, do so well."

Symptoms and signs of Graves disease

Epub: Daniels et al. Alemtuzumab-Related Thyroid Dysfunction in a Phase 2 Trial of Patients with Relapsing-RemittingMultiple Sclerosis.J Clin Endocrinol Metab. 2013 Oct.

Context: Alemtuzumab, an anti-CD52 monoclonal antibody, increased risk of thyroid dysfunction in CAMMS223, a phase 2 trial in RRMS.

Objective: Detailed description of thyroid dysfunction in CAMMS223.

Design: RRMSers (n=334) were randomized 1:1:1 to 44 mcg subcutaneous interferon beta-1a (SC IFNB-1a, Rebif®) or annual courses of 12 or 24 mg intravenous alemtuzumab. Thyroid function tests (TSH, free T3, free T4) and thyrotropin-binding inhibitory immunoglobulin (TBII) were assessed at screening, month 1, and quarterly thereafter; anti-thyroid peroxidase antibodies were assessed at screening and every 6 months. Thyroid dysfunction episodes were categorized post hoc by an endocrinologist.

Results: During median follow-up of 57.3 months, 34% of alemtuzumab and 6.5% of SC IFNB-1a study subjects had thyroid dysfunction (p<0.0001). Ten percent of alemtuzumab and 3% of SC IFNB-1a MSers had >1 episode of thyroid dysfunction. With alemtuzumab, Graves' hyperthyroidism occurred in 22%, hypothyroidism in 7%, and subacute thyroiditis in 4%. Of MSers with overt Graves' hyperthyroidism, 23% spontaneously became euthyroid and an additional 15% spontaneously developed hypothyroidism. Of MSers with overt hypothyroidism, 74% were TBII-positive. Annual incidence of first episode of thyroid dysfunction increased each year through year 3, then decreased each subsequent study year.

Conclusions: Thyroid dysfunction was more common with alemtuzumab than with SC IFNB-1a. There were few serious episodes. Regular monitoring facilitated early detection. Unique features of this population included high prevalence of Graves' hyperthyroidism, multiple episodes of thyroid dysfunction in individual MSers, spontaneous hypothyroidism following overt Graves' hyperthyroidism, and a high prevalence of TBII-positive overt hypothyroidism.

CoI: multiple

8 comments:

  1. How long until we find out if it will be available in the uk?

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    1. It is in the hands of NICE. I attended an alemtuzumab launch meeting in Copenhagen on Friday. I heard at the meeting that the first German MSers is due to be infused tomorrow.

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  2. Prof G,

    I know of many who have done \ are doing very well after two Alemtuzumab infusions. How does it fit with your ebv / herv hypothesis?

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    1. Very well. Alemtuzumab is a B cell depleter therefore it targets EBV. Not sure about HERVs we will need to do the studies.

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  3. I already take synthroid so not worried about Graves disease. Thrombocytic purpura is the intimidating side effect. 1 in 100 is rare, but not too rare. Would appreciate further comment or explaination. Blood clotting issues seem quite dangerous,

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  4. Any views on today's extremely negative FDA staff briefing documents? Is Alemtuzumab doomed in the US? I'd be grateful for any thoughts. Here are the two documents as well as one from Genzyme:

    http://www.fda.gov/advisorycommittees/committeesmeetingmaterials/drugs/peripheralandcentralnervoussystemdrugsadvisorycommittee/ucm374183.htm

    Also, the URL below is for a discussion forum related to the Genzyme security specific to this drug.

    Thanks for any thoughts.

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  5. I have Hashimoto's hypothyroidism. Would I still be able to take Alemtuzumab?

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