Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab
| Autor: | Wiendl, Heinz, Carraro, Matthew, Comi, Giancarlo, Izquierdo, Guillermo, Kim, Ho Jin, Sharrack, Basil, Tornatore, Carlo, Daizadeh, Nadia, Chung, Luke, Jacobs, Alan K, Hogan, Richard J, Wychowski, Linda V, Van Wijmeersch, Bart, CARE-MS I, CARE-MS II, and CAMMS03409 Investigators |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Lymphocyte medicine.disease_cause Autoimmunity 0302 clinical medicine Recurrence Lymphocytes Alemtuzumab biology Middle Aged medicine.anatomical_structure Neurology Female Kidney Diseases medicine.drug Adult Adolescent Cells CD3 Update Article Autoimmune Diseases Depletion 03 medical and health sciences Young Adult Multiple Sclerosis Relapsing-Remitting medicine Humans Immunologic Factors Lymphocyte Count Remitting Multiple-Sclerosis business.industry Multiple sclerosis medicine.disease Thrombocytopenia Thyroid Diseases 030104 developmental biology Peripheral blood lymphocyte Pharmacodynamics Immunology biology.protein Therapy Neurology (clinical) business 030217 neurology & neurosurgery CD8 |
| Zdroj: | Neurology® Neuroimmunology & Neuroinflammation Article |
| Popis: | ObjectiveTo examine the association between peripheral blood lymphocyte pharmacodynamics and autoimmune adverse events (AEs) or return of disease activity in alemtuzumab-treated patients with relapsing-remitting MS.MethodsPatients received 2 alemtuzumab courses (12 mg/d IV; 5 days at baseline, 3 days 12 months later) in the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis studies (NCT00530348 and NCT00548405) and could then receive as-needed alemtuzumab or other disease-modifying therapy in a 4-year extension (NCT00930553). Lymphocytes were phenotyped quarterly over 2 years using fluorescence-activated cell sorting. Pharmacodynamic assessments included counts of total lymphocytes, CD3+ T cells, CD4+/CD8+ T cells (total/naive/memory/regulatory [Treg]), and CD19+ B cells (total/immature/mature/memory) and ratios of CD19+ (total/immature/mature/memory) to Treg (CD4+/CD8+) counts. Assessed autoimmune AEs included immune thrombocytopenia, nephropathies, and thyroid events. Efficacy assessments included relapses, 6-month confirmed disability worsening (CDW), and MRI disease activity.ResultsLymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19+ to Treg cell count ratios), showed no significant differences over 2 years in patients developing/not developing autoimmune AEs, relapses, CDW, or MRI activity through 6 years following alemtuzumab. Lymphocyte kinetics were also unrelated to multiple autoimmune AEs or extreme clinical phenotypes.ConclusionsRepopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|