I have just received an email to say that the person with MS, who I discuss above, is going to be given a third cycle of alemtuzumab. Apparently her neurologist now agrees that the development of an autoimmune disease after alemtuzumab should not be a contraindication to repeat courses.
I find this so rewarding as it shows that MS=Selfie is making a difference to the management of MS in real life.
This is based on the regulators worldview of MS being 3 diseases and not one, i.e. RRMS, SPMS and PPMS. The alemtuzumab trials were done in early RRMS patients.
Besides the outcome of the trials based on treating only RRMS patients, would it just be worthless to trial the drug on patients with progressive disease? In other words, are the progressive forms of MS already universally known as being beyond the point of help from this type of drug?
Not at all. We are doing a lot of exciting trials in patients with more advanced MS and I think the Pharmaceutical industry notes they have to target more advanced MS as well.
Thanks for posting the case study! A question about autoimmunity - I saw a paper linking the development of autoimmune thyroid disease to better outcomes with alemtuzumab treatment. Do you think thyroid disease is beneficial in MS and therefore using a B cell depleter to control the repopulation of B cells and reduce autoimmunity could reduce the efficacy of alemtuzumab?
The following is the paper you are referring to. It is too small to draw conclusions, but suggest autoimmune thyroid disease may be associated with the immunological changes that put people into long-term remission.
Sovetkina et al. Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response. J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa453.
Context: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect.
Objective: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not.
Design, setting, and patients: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center.
Main outcome measures: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated.
Results: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups.
Conclusion: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.
I have just received an email to say that the person with MS, who I discuss above, is going to be given a third cycle of alemtuzumab. Apparently her neurologist now agrees that the development of an autoimmune disease after alemtuzumab should not be a contraindication to repeat courses.
I find this so rewarding as it shows that MS=Selfie is making a difference to the management of MS in real life.
I have an indirectly related question…
Is Lemtrada contraindicated for progressive MS? If so, what is the thinking behind it?
This is based on the regulators worldview of MS being 3 diseases and not one, i.e. RRMS, SPMS and PPMS. The alemtuzumab trials were done in early RRMS patients.
Besides the outcome of the trials based on treating only RRMS patients, would it just be worthless to trial the drug on patients with progressive disease? In other words, are the progressive forms of MS already universally known as being beyond the point of help from this type of drug?
Not at all. We are doing a lot of exciting trials in patients with more advanced MS and I think the Pharmaceutical industry notes they have to target more advanced MS as well.
Also 'concomitant autoimmune diseases' is not a contraindication for lemtrada in the US, may help the argument.
Yes, I agree.
Thanks for posting the case study! A question about autoimmunity - I saw a paper linking the development of autoimmune thyroid disease to better outcomes with alemtuzumab treatment. Do you think thyroid disease is beneficial in MS and therefore using a B cell depleter to control the repopulation of B cells and reduce autoimmunity could reduce the efficacy of alemtuzumab?
The following is the paper you are referring to. It is too small to draw conclusions, but suggest autoimmune thyroid disease may be associated with the immunological changes that put people into long-term remission.
Sovetkina et al. Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response. J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa453.
Context: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect.
Objective: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not.
Design, setting, and patients: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center.
Main outcome measures: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated.
Results: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups.
Conclusion: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.
Thanks for this!