Contributions
Abstract: P934
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab (ALZ) belongs to the pulsed immune reconstitution therapies for relapsing-remitting multiple sclerosis (RRMS) consisting of two annual courses of 5 and 3 days. Each infusion causes pan-lymphocyte depletion, followed by a reconstitution of the lymphocyte repertoire. ALZ therapy is associated with an increased risk for secondary autoimmune diseases (SAD). There is no laboratory test that predicts this risk.
Objective/Aim: We investigated if the occurrence of autoimmune antibodies anticipated the development of SAD in RRMS patients treated with ALZ.
Methods: RRMS patients were consecutively included. Serum samples were obtained prior to ALZ and at 12 and 24 months of follow-up for analyses of autoantibodies (thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), glutamic acid decarboxylase antibodies (GADAb), islet cell antibodies (ICA) and anti-glomerular basement membrane antibodies (GBMAb)). The temporal relationship between ALZ induction of autoantibodies and the development of SAD was analyzed.
Results: Fifty-one (30 females) RRMS patients were included in the study. At baseline 3(6%, n=48) patients had positive TgAb, 2(4%) positive TPOAb and none were positive for GADAb, ICA or GBMAb. Upon follow-up at 12 months, the corresponding values were 9(18%, n=51), 11(22%), 1(2%), 1(2%), and 0, and at 24 months they were 12(28%, n=43), 13(30%), 1(2%), 1(2%), and 0. At 24 months of follow-up, 22(43%, n=51) patients had developed SAD; 20(39%) autoimmune thyroid disorders and 2(4%) immune thrombocytopenia (ITP). Mean time from baseline to diagnosis of autoimmune thyroid disorder was 18(SD 7) months and for those with ITP 21(SD 8). Thirteen (65%) of those who developed autoimmune thyroid disorder had positive TgAb and TPOAb at diagnosis, mean time from detection of autoantibodies to the development of low thyroid-stimulating hormone (TSH) values was 7.5(SD 9.6) months. All patients with positive thyroid autoantibodies at baseline (n=3) developed autoimmune thyroid disorder. One (2%) patient developed positive autoantibodies for GADAb and ICA but did not develop a corresponding SAD.
Conclusion: In this in prospectively followed real world cohort of RRMS patients treated with ALZ, the development of secondary autoimmunity was higher than in the pivotal studies of ALZ. Increased thyroid autoantibodies seem to be a risk factor and a predictor of secondary autoimmune thyroid disorder.
Disclosure: SS and LN has nothing to disclose. MA has received compensation for lectures and/ or advisory boards from Biogen, Genzyme, and Novartis. JL has received travel support and/ or lecture honoraria from Biogen, Novartis, Teva and Genzyme/ SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/ SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva. CM has received honoraria for lectures and advisory boards from Biogen, Merck, Novartis, Roche and SanofiAventis.
Abstract: P934
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab (ALZ) belongs to the pulsed immune reconstitution therapies for relapsing-remitting multiple sclerosis (RRMS) consisting of two annual courses of 5 and 3 days. Each infusion causes pan-lymphocyte depletion, followed by a reconstitution of the lymphocyte repertoire. ALZ therapy is associated with an increased risk for secondary autoimmune diseases (SAD). There is no laboratory test that predicts this risk.
Objective/Aim: We investigated if the occurrence of autoimmune antibodies anticipated the development of SAD in RRMS patients treated with ALZ.
Methods: RRMS patients were consecutively included. Serum samples were obtained prior to ALZ and at 12 and 24 months of follow-up for analyses of autoantibodies (thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), glutamic acid decarboxylase antibodies (GADAb), islet cell antibodies (ICA) and anti-glomerular basement membrane antibodies (GBMAb)). The temporal relationship between ALZ induction of autoantibodies and the development of SAD was analyzed.
Results: Fifty-one (30 females) RRMS patients were included in the study. At baseline 3(6%, n=48) patients had positive TgAb, 2(4%) positive TPOAb and none were positive for GADAb, ICA or GBMAb. Upon follow-up at 12 months, the corresponding values were 9(18%, n=51), 11(22%), 1(2%), 1(2%), and 0, and at 24 months they were 12(28%, n=43), 13(30%), 1(2%), 1(2%), and 0. At 24 months of follow-up, 22(43%, n=51) patients had developed SAD; 20(39%) autoimmune thyroid disorders and 2(4%) immune thrombocytopenia (ITP). Mean time from baseline to diagnosis of autoimmune thyroid disorder was 18(SD 7) months and for those with ITP 21(SD 8). Thirteen (65%) of those who developed autoimmune thyroid disorder had positive TgAb and TPOAb at diagnosis, mean time from detection of autoantibodies to the development of low thyroid-stimulating hormone (TSH) values was 7.5(SD 9.6) months. All patients with positive thyroid autoantibodies at baseline (n=3) developed autoimmune thyroid disorder. One (2%) patient developed positive autoantibodies for GADAb and ICA but did not develop a corresponding SAD.
Conclusion: In this in prospectively followed real world cohort of RRMS patients treated with ALZ, the development of secondary autoimmunity was higher than in the pivotal studies of ALZ. Increased thyroid autoantibodies seem to be a risk factor and a predictor of secondary autoimmune thyroid disorder.
Disclosure: SS and LN has nothing to disclose. MA has received compensation for lectures and/ or advisory boards from Biogen, Genzyme, and Novartis. JL has received travel support and/ or lecture honoraria from Biogen, Novartis, Teva and Genzyme/ SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/ SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva. CM has received honoraria for lectures and advisory boards from Biogen, Merck, Novartis, Roche and SanofiAventis.