ClinicSpeak: secondary autoimmunity post-alemtuzumab

Secondary autoimmunity occurs in ~50% of MSers treated with alemtuzumab. #ClinicSpeak #MSBlog #MSResearch

"The following post is in response to yesterday's ClinicSpeak post on natalizumab vs. alemtuzumab and the question about secondary autoimmunity post-alemtuzumab."

"The abstract below summarises the long-term follow-up of the alemtuzumab-treated MSers in Cambridge. Overall they do very well; 60% of MSers had a stabilization or improvement in their disability. Please note that almost 50% of treated MSers developed secondary autoimmunity as a consequence of alemtuzumab treatment; a stark reminder that a decision to be treated with alemtuzumab needs to be taken seriously and that you need to highly motivated and adherent with the strict monitoring programme to detect these complications."

The following are some excerpts from the paper in relation to secondary autoimmunity:

....Clinical autoimmune disease developed in 41 patients (48%, omitting one patient with pre-existing thyroid disease); a further 12 (14%) patients developed sustained novel autoantibodies (9 anti-nuclear antibodies and 3 anti-thyroid peroxidase antibodies) with no evidence of associated clinical disease....

..... This occurred a median of 16 months since last treatment ... 

.... Autoimmunity was not associated with the number of alemtuzumab treatment cycles administered....

..... Thyroid autoimmunity developed in 41% of whom 63% had hyperthyroidism (Graves’ disease); 1 patient had transient thyroiditis, and 34% developed primary hypothyroidism with positive antithyroid peroxidase antibodies... 

... Most patients were treated medically; three with Graves’ disease also required radio-iodine treatment..... 

..... Three patients (3.5%) developed immune thrombocytopenic purpura (ITP).... 

..... Asymptomatic autoimmune neutropenia developed in a single patient 3 months after her second alemtuzumab cycle....

..... One patient developed autoimmune haemolytic anaemia, which was detected on full blood count monitoring.. 

.... One patient developed Goodpasture’s disease requiring renal  transplantation.... 

"In addition to these cases I am aware of a patient developing bullous skin disease (bullous pemphigoid) post-alemtuzumab. Based on the spectrum of secondary autoimmune diseases that are seen in the bone marrow transplant setting, I predict that we will see thrombotic thrombocytopenic purpura (TTP), which is also a severe potentially life-threatening antibody mediated autoimmune disease of clotting, myasthenia gravis and others; however, these will be very rare."

"In conclusion, although secondary autoimmunity post alemtuzumab is common, the majority will be related to the thyroid and relatively easy  to manage. The rarer potentially life-threatening autoimmune diseases will be detected with screening and if treated early should be a manageable risk. Please let me know if you need any other information."

ITP

Epub: Tuohy et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. J Neurol Neurosurg Psychiatry. 2014 May 21. pii: jnnp-2014-307721. doi: 10.1136/jnnp-2014-307721.

OBJECTIVES: Alemtuzumab is a newly licensed treatment of active relapsing-remitting multiple sclerosis (RRMS) in Europe, which in phase II and III studies demonstrated superior efficacy over β-interferon in reducing disability progression over 2-3 years. In this observational cohort study, we sought to describe our longer-term experience of the efficacy and safety of alemtuzumab in active RRMS.


METHODS: Clinical and laboratory data including serial Expanded Disability Status Scale (EDSS) assessments, from all 87 MSers treated with alemtuzumab on investigator-led studies in Cambridge, UK, from 1999 to 2012, were collected. The occurrence of adverse events including secondary autoimmunity, malignancy and death, and pregnancy outcomes was recorded. Baseline variables including age, disease duration and relapse rate were compared in univariate and logistic regression analyses between groups with different disability outcomes.


RESULTS: Over a median 7-year follow-up (range 33-144 months), most MSers (52%) required just two cycles of alemtuzumab. In the remaining MSers, relapses triggered re-treatment to a total of three cycles (36%), four cycles (8%) or five cycles (1%). Using a 6-month sustained accumulation of disability definition, 59/87 (67.8%) of MSers had an improved or unchanged disability compared with baseline. By an area under the curve analysis, 52/87 (59.8%) MSers had an overall improvement or stabilisation of disability. Higher baseline relapse rate was associated with worse long-term disability outcomes, with trends for longer disease duration and older age at first treatment. Secondary autoimmunity was the most frequent adverse event occurring in 41/86 (47.7%) MSers, most commonly involving the thyroid gland.

CONCLUSIONS: Alemtuzumab is associated with disease stabilisation in the majority of MSers with highly active RRMS over an average seven-year follow-up. No new safety concerns arose over this extended follow-up.

CoI: multiple

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