ClinicSpeak: frontloading risk; not one but two autoimmune diseases

Are you prepared to trade-in MS for one, or maybe two, other autoimmune diseases? #ClinicSpeak #MSBlog #MSResearch

"Are you prepared to trade in your MS, on the promise of long-term remission, for a second autoimmune disease? If not alemtuzumab is not for you. The two case reports below are of two MSers who developed both autoimmune thrombocytopenia and autoimmune thyroid disease after their first course of alemtuzumab. Interestingly, both these MSers had previously been treated with fingolimod with marked lymphopaenia. Is it possible previous fingolimod treatment predisposes you to secondary autoimmunity? We will learn very quickly as many MSers in our centre are transitioning from natalizumab to alemtuzumab via a fingolimod bridge."

"Please note that one of the selling points for alemtuzumab is pregnancy, i.e. you can fall pregnant ~4 months after having a course of treatment with no drug on board. However, if you develop autoimmunity whilst pregnant the auto-antibodies can cross the placenta and affect the unborn foetus. For thyroid disease this may not be such a big problem (transient neonatal hyperthyroidism), but this may be much more serious for autoimmune thrombocytopenia and kidney disease. Please note that the secondary autoimmune complications of alemtuzumab treatment are frontloaded; if you get through 5 years (4 years post last course) you are likely not to get the secondary autoimmune complications. However, the 4 year rule does not answer the other major outstanding question of delayed secondary malignancies post-alemtuzumab. The latter  question will only be answered after thousands of treated MSer go beyond 10, or even 20, years of follow-up; the same timeframe we require to see if the long-term remission becomes a cure in a proportion of MSers."

Frontloading Risk!

Obermann et al. Simultaneous early-onset immune thrombocytopenia and autoimmune thyroid disease following alemtuzumab treatment in relapsing-remitting multiple sclerosis. Mult Scler. 2016 Mar 15. pii: 1352458516638558.

OBJECTIVE: We report two cases of patients with relapsing-remitting multiple sclerosis with early-onset thrombocytopenia and autoimmune thyroid disease after the first treatment course with 60-mg alemtuzumab.

METHODS: Case series and review of the literature.

RESULTS: Both patients showed severe thrombocytopenia with platelet counts of 2 × 109 and 11 × 109/L, respectively, as well as increased thyroid antibodies within only a few months after initiating alemtuzumab treatment (11 and 9 months). Both patients responded considerably well to medical therapy including corticosteroids and intravenous immunoglobulins with slow platelet recovery over several weeks. Interestingly, both patients were previously treated with fingolimod and showed a marked lymphocytopenia that led to discontinuation.

CONCLUSION: These cases emphasize the necessity of careful clinical surveillance and proper education of patients treated with alemtuzumab as proposed by the safety-monitoring program. Previous severe lymphocytopenia under therapy with other disease-modifying therapies may be a risk factor for the development of immune thrombocytopenia.

CoI: multiple

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