A new spin on immune reconstitution

A

We’ve all heard of alemtuzumab induced thyroid autoimmunity; a side effect affecting roughly 30-48% of individuals receiving the treatment. It is believed to occur when immune cells, particularly autoreactive IgG+ memory B cells return early following depletion of the lymphocytes, leading to a breakdown in the immune tolerance towards the thyroid.

But, according to this case report, an individual starting ocrelizumab for their primary progressive MS also developed thyroid autoimmunity after their initial infusion of ocrelizumab. It resolved relatively quickly without treatment (see Table below), which can also happen with alemtuzumab induced thyroid autoimmunity. Subsequent infusions didn’t seem to affect the thyroid function and the individual remained in remission.

Ocrelizumab doesn’t cause immune depletion to the extent that alemtuzumab does, the biological milieu that can lead to immune reconstitution issues. It is therefore interesting that the thyroid disease occurred. Equally interesting is that it occurred in the face of depleted memory B cells which occurs very quickly after the initial treatment.

We don’t routinely monitor thyroid function in ocrelizumab and may need to re-consider this. It also means that thyroid autoimmunity after immune reconstitution in MS is not as straightforward as we previously thought.

Table 1: Pre and post ocrelizumab treatment values (1st dose Jul 2018, 2nd Jan 2019, 3rd Jul 2019, 4th Feb 2020)

Abstract

Endocr Regul. 2021 Sep 13;55(3):169-173. doi: 10.2478/enr-2021-0018.

Graves’ disease with spontaneous resolution following ocrelizumab in primary progressive multiple sclerosis

Diana Borges Duarte Ana Martins da Silva  Claudia Freitas  Helena Cardoso 

Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves’ disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.

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Neuro Doc Gnanapavan

4 comments

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  • I wonder if the parathyroid gland may be similarly affected? FYI I have had 4 cycles of Ocrelizumab; following the first 2 my parathyroid levels were marginally elevated. After an 11 month wait [!] last week I had a consultation {telephone} with an endocrinologist who has ordered further blood tests, and a 24 hour urine collection. Ironically she seems most concerned about it. I’ll keep my MS team informed about the outcome but thought it may be of some interest to you and to those reading your post.

  • A single case doesn’t seem enough to justify any speculation that ocrelizumab causes Graves Disease or any such problem

    This could be a simple coincidence

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