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000163492 041__ $$aEnglish
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000163492 1001_ $$0P:(DE-2719)9000850$$aScheibe, Franziska$$b0$$udzne
000163492 245__ $$aDaratumumab for treatment-refractory antibody-mediated diseases in neurology.
000163492 260__ $$aOxford$$bBlackwell Science$$c2022
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000163492 520__ $$aA fraction of patients with antibody-mediated autoimmune diseases remain unresponsive to first-/second-line and sometimes even to escalation immunotherapies. Because these patients are still affected by poor outcome and increased mortality, we investigated the safety and efficacy of the plasma cell-depleting anti-CD38 antibody daratumumab in life-threatening, antibody-mediated autoimmune diseases.In this retrospective, single-center case series, seven patients with autoantibody-driven neurological autoimmune diseases (autoimmune encephalitis, n = 5; neurofascin antibody-associated chronic inflammatory demyelinating polyneuropathy associated with sporadic late onset nemaline myopathy, n = 1; seronegative myasthenia gravis, n = 1) unresponsive to a median of four (range = 4-9) immunotherapies were treated with four to 20 cycles of 16 mg/kg daratumumab.Daratumumab allowed a substantial clinical improvement in all patients, as measured by modified Rankin Scale (mRS; before treatment: mRS =5, n = 7; after treatment: median mRS =4, range = 0-5), Clinical Assessment Scale in Autoimmune Encephalitis (from median 21 to 3 points, n = 5), Inflammatory Neuropathy Cause and Treatment disability score (from 7 to 0 points, n = 1), and Quantitative Myasthenia Gravis score (from 16 to 8 points, n = 1). Daratumumab induced a substantial reduction of disease-specific autoreactive antibodies, total IgG (serum, 66%, n = 7; cerebrospinal fluid, 58%, n = 5), and vaccine-induced titers for rubella (50%) and tetanus toxoid (74%). Treatment-related toxicities Grade 3 or higher occurred in five patients, including one death.Our findings suggest that daratumumab provided a clinically relevant depletion of autoreactive long-lived plasma cells, identifying plasma cell-targeted therapies as promising escalation therapy for highly active, otherwise treatment-refractory autoantibody-mediated neurological diseases.
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000163492 650_7 $$2Other$$aCIDP
000163492 650_7 $$2Other$$aautoimmune encephalitis
000163492 650_7 $$2Other$$adaratumumab
000163492 650_7 $$2Other$$amyasthenia gravis
000163492 650_7 $$2Other$$asporadic late onset nemaline myopathy
000163492 650_2 $$2MeSH$$aAntibodies, Monoclonal
000163492 650_2 $$2MeSH$$aAutoantibodies
000163492 650_2 $$2MeSH$$aEncephalitis
000163492 650_2 $$2MeSH$$aHashimoto Disease
000163492 650_2 $$2MeSH$$aHumans
000163492 650_2 $$2MeSH$$aMyasthenia Gravis
000163492 650_2 $$2MeSH$$aNervous System Diseases: drug therapy
000163492 650_2 $$2MeSH$$aNeurology
000163492 650_2 $$2MeSH$$aRetrospective Studies
000163492 7001_ $$00000-0003-3553-6406$$aOstendorf, Lennard$$b1
000163492 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b2$$udzne
000163492 7001_ $$aRadbruch, Helena$$b3
000163492 7001_ $$aAschman, Tom$$b4
000163492 7001_ $$aHoffmann, Sarah$$b5
000163492 7001_ $$aBlau, Igor-Wolfgang$$b6
000163492 7001_ $$aMeisel, Christian$$b7
000163492 7001_ $$aAlexander, Tobias$$b8
000163492 7001_ $$aMeisel, Andreas$$b9
000163492 77318 $$2Crossref$$3journal-article$$a10.1111/ene.15266$$bWiley$$d2022-02-10$$n6$$p1847-1854$$tEuropean Journal of Neurology$$v29$$x1351-5101$$y2022
000163492 773__ $$0PERI:(DE-600)2020241-6$$a10.1111/ene.15266$$gp. ene.15266$$n6$$p1847-1854$$tEuropean journal of neurology$$v29$$x1351-5101$$y2022
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