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OP69 – 2651: Safety and effect of fingolimod on no evidence of disease activity (NEDA-4) in young adult patients with relapsing-remitting multiple sclerosis
S22
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
with a first demyelinating event with or without MOG antibodies only rarely autoantibodies against neuronal surface antigens are detected.
OP68 - 2605 Tumefactive demyelinating lesions in juvenile-onset multiple sclerosis S. Menascu, S. Miron. Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer & Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Objective: To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenileonset MS. Methods: Six patients (2 boys, 4 girls, age 14.7±2.4 years) diagnosed with MS were analyzed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion center on 2–3 consecutive slices. Results: We report on six patients with 6 TDL, which developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. The two other patients progressed rapidly to develop seizures, became stuporotic and were admitted to the pediatric intensive care unit. Brain MRI demonstrated six TDLs, with a TDL volume of 4.7±0.4 cm3 (mean ± SD), accompanied by peri-lesional edema and ring enhancement. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions with a volume of 0.72±0.21 cm3 . Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences: apparent diffusion coefficient (ADC) and radial diffusivity (RD) values (×10–3 ) were significantly higher in TDLs: for ADC, 1.82±0.05 versus 1.02±0.08 (p<0.03); for RD 1.72±0.04 versus 1.08±0.03 (p<0.01). Fractional anisotropy (FA) values were significantly lower in TDL compared to chronic lesions, 0.13±0.03 versus 0.25±0.02, (p<0.01). Conclusion: TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and edema. The different metrics of chronic lesions suggests a different microstructure due to pro-sclerotic tissue reorganization and reduced edema in chronic MS lesions. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.
OP69 - 2651 Safety and effect of fingolimod on no evidence of disease activity (NEDA-4) in young adult patients with relapsing-remitting multiple sclerosis B. Bajer-Kornek, A. Ghezzi, G. Karlsson, D. Häering, J. Gärtner, T. Chitnis, D. Pohl, N. Putzki. Department of Neurology, Medical University of Vienna, Vienna, Austria Objective: To evaluate the safety and effect of fingolimod 0.5 mg on NEDA-4 in young adult RRMS patients. NEDA-4 is a combined 4-part measure (no new/enlarging T2 lesions; no confirmed relapses; no 6-month confirmed disability progression; annualized rate of brain atrophy <0.4%) and has been proposed as a comprehensive measure of absence of disease activity or worsening at MRI and clinical levels in relapsing-remitting multiple sclerosis (RRMS). Methods: Post-hoc analysis of NEDA-4 was conducted in the combined FREEDOMS/FREEDOMS II (2-year studies versus placebo), and in TRANSFORMS (1-year study versus intramuscular interferon-beta-1a, IFN). NEDA-4 was analyzed by logistic regression model (adjusted for treatment, age at baseline, treatment-by-age interaction). Proportion of patients with NEDA-4 and odds ratios (OR) versus controls were estimated for
19s (2015) S1 – S152
ages ≤30 years and >30 years. Safety in patients ≤30 years was evaluated from AEs reported on fingolimod (N=1364) and placebo (N=966) using combined data from all fingolimod phase II/III RRMS studies. Results: In young adults (≤30 years) from FREEDOMS/FREEDOMS II, 24/153 (15.7%) had NEDA-4 on fingolimod versus 4/141 (2.8%) on placebo (OR=6.37, p<0.001). In TRANSFORMS, 22/105 (21%) had NEDA-4 on fingolimod versus 9/103 (8.7%) on IFN (OR=2.77, p<0.05). Similar effects were seen for patients >30 years. The fingolimod AE profile in young adults was consistent with the known profile of fingolimod in the overall population. Conclusion: Young adults were approximately 3–6 times more likely to achieve NEDA-4 on fingolimod versus controls. Efficacy and safety of fingolimod in young patients will be further investigated in the PARADIGMS study (fingolimod versus IFN in pediatric MS), currently recruiting worldwide.
OP70 - 2417 Plasma exchange (PLEX) in pediatric neurologic diseases: Assessment of safety and efficacy S. Bigi, C. Licht, M. Twilt, S.M. Benseler. Division of Neurology, University Children’s Hospital Bern, Bern, Switzerland AND Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada Objective: We aim to assess the indication, safety and outcome of PLEX in pediatric patients with neurologic diseases. Methods: Retrospective cohort study of consecutive patients seen in the dialysis and apheresis clinic of a tertiary care center between April 2007 and March 2013. Included were all pediatric patients treated with PLEX for an underlying neurologic disease. Adverse events (AE) were recorded according to the Common Terminology Criteria for Adverse Events classification. The key neurological deficit was graded as none, mild (fully ambulatory, no impact on activities of daily living (ADL)), moderate (limiting ambulation and/or ADL), and severe (wheelchair/bed ridden and/or ventilated), assessed at beginning/end of PLEX, at discharge from the acute care facility and at last clinical encounter. Primary outcome was the neurological deficit at last clinical encounter. Results: A total of 109 (48 female, 44%) patients received PLEX. Eighteen (12%; 13 female (72%)) had an underlying neurologic disease consisting of: demyelinating (10), antibody-associated (2), other inflammatory neurologic diseases (6). Indication for PLEX was failure of first line treatment in all but one patient. Median (range) age at PLEX was 10.8 years (0.8–17.9 years). The key neurological deficit at PLEX start was severe in 15 (83%) and moderate in three (17%) patients. A total of 39 AE were recorded, consisting of hypotension (8), allergic reaction (3), anemia (15), thrombosis (2) and hypocalcemia (11). Twelve (31%) AE were graded as severe. At discharge from the acute care facility, six patients (33%) were ambulatory with support. At last clinical encounter after a median (range) follow up time of 2.0 years (0.3–6.6 years), the neurological deficit was none/mild in ten patients (59%). Conclusion: For pediatric patients with severe inflammatory neurologic diseases PLEX is a safe treatment option. One third showed early improvement and almost 60% regained independent ambulation over the follow up period.
OP71 - 2706 Autologous hematopoietic stem cell transplantation in pediatric multiple sclerosis: Long-time follow-up K.I. Kirgizov, E.Y. Volkova, E.V. Skorobogatova, S.V. Piliya, A.A. Bologov, R.C. Bembeeva, N.N. Zavadenko. Department of Bone Marrow Transplantation, The Russian Children’s Research Hospital, Moscow, Russia Objective: Autologous hematopoietic stem cell transplantation (Auto-HSCT) is the method of choice for patients with refractory
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
with a first demyelinating event with or without MOG antibodies only rarely autoantibodies against neuronal surface antigens are detected.
OP68 - 2605 Tumefactive demyelinating lesions in juvenile-onset multiple sclerosis S. Menascu, S. Miron. Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer & Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Objective: To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenileonset MS. Methods: Six patients (2 boys, 4 girls, age 14.7±2.4 years) diagnosed with MS were analyzed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion center on 2–3 consecutive slices. Results: We report on six patients with 6 TDL, which developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. The two other patients progressed rapidly to develop seizures, became stuporotic and were admitted to the pediatric intensive care unit. Brain MRI demonstrated six TDLs, with a TDL volume of 4.7±0.4 cm3 (mean ± SD), accompanied by peri-lesional edema and ring enhancement. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions with a volume of 0.72±0.21 cm3 . Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences: apparent diffusion coefficient (ADC) and radial diffusivity (RD) values (×10–3 ) were significantly higher in TDLs: for ADC, 1.82±0.05 versus 1.02±0.08 (p<0.03); for RD 1.72±0.04 versus 1.08±0.03 (p<0.01). Fractional anisotropy (FA) values were significantly lower in TDL compared to chronic lesions, 0.13±0.03 versus 0.25±0.02, (p<0.01). Conclusion: TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and edema. The different metrics of chronic lesions suggests a different microstructure due to pro-sclerotic tissue reorganization and reduced edema in chronic MS lesions. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.
OP69 - 2651 Safety and effect of fingolimod on no evidence of disease activity (NEDA-4) in young adult patients with relapsing-remitting multiple sclerosis B. Bajer-Kornek, A. Ghezzi, G. Karlsson, D. Häering, J. Gärtner, T. Chitnis, D. Pohl, N. Putzki. Department of Neurology, Medical University of Vienna, Vienna, Austria Objective: To evaluate the safety and effect of fingolimod 0.5 mg on NEDA-4 in young adult RRMS patients. NEDA-4 is a combined 4-part measure (no new/enlarging T2 lesions; no confirmed relapses; no 6-month confirmed disability progression; annualized rate of brain atrophy <0.4%) and has been proposed as a comprehensive measure of absence of disease activity or worsening at MRI and clinical levels in relapsing-remitting multiple sclerosis (RRMS). Methods: Post-hoc analysis of NEDA-4 was conducted in the combined FREEDOMS/FREEDOMS II (2-year studies versus placebo), and in TRANSFORMS (1-year study versus intramuscular interferon-beta-1a, IFN). NEDA-4 was analyzed by logistic regression model (adjusted for treatment, age at baseline, treatment-by-age interaction). Proportion of patients with NEDA-4 and odds ratios (OR) versus controls were estimated for
19s (2015) S1 – S152
ages ≤30 years and >30 years. Safety in patients ≤30 years was evaluated from AEs reported on fingolimod (N=1364) and placebo (N=966) using combined data from all fingolimod phase II/III RRMS studies. Results: In young adults (≤30 years) from FREEDOMS/FREEDOMS II, 24/153 (15.7%) had NEDA-4 on fingolimod versus 4/141 (2.8%) on placebo (OR=6.37, p<0.001). In TRANSFORMS, 22/105 (21%) had NEDA-4 on fingolimod versus 9/103 (8.7%) on IFN (OR=2.77, p<0.05). Similar effects were seen for patients >30 years. The fingolimod AE profile in young adults was consistent with the known profile of fingolimod in the overall population. Conclusion: Young adults were approximately 3–6 times more likely to achieve NEDA-4 on fingolimod versus controls. Efficacy and safety of fingolimod in young patients will be further investigated in the PARADIGMS study (fingolimod versus IFN in pediatric MS), currently recruiting worldwide.
OP70 - 2417 Plasma exchange (PLEX) in pediatric neurologic diseases: Assessment of safety and efficacy S. Bigi, C. Licht, M. Twilt, S.M. Benseler. Division of Neurology, University Children’s Hospital Bern, Bern, Switzerland AND Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada Objective: We aim to assess the indication, safety and outcome of PLEX in pediatric patients with neurologic diseases. Methods: Retrospective cohort study of consecutive patients seen in the dialysis and apheresis clinic of a tertiary care center between April 2007 and March 2013. Included were all pediatric patients treated with PLEX for an underlying neurologic disease. Adverse events (AE) were recorded according to the Common Terminology Criteria for Adverse Events classification. The key neurological deficit was graded as none, mild (fully ambulatory, no impact on activities of daily living (ADL)), moderate (limiting ambulation and/or ADL), and severe (wheelchair/bed ridden and/or ventilated), assessed at beginning/end of PLEX, at discharge from the acute care facility and at last clinical encounter. Primary outcome was the neurological deficit at last clinical encounter. Results: A total of 109 (48 female, 44%) patients received PLEX. Eighteen (12%; 13 female (72%)) had an underlying neurologic disease consisting of: demyelinating (10), antibody-associated (2), other inflammatory neurologic diseases (6). Indication for PLEX was failure of first line treatment in all but one patient. Median (range) age at PLEX was 10.8 years (0.8–17.9 years). The key neurological deficit at PLEX start was severe in 15 (83%) and moderate in three (17%) patients. A total of 39 AE were recorded, consisting of hypotension (8), allergic reaction (3), anemia (15), thrombosis (2) and hypocalcemia (11). Twelve (31%) AE were graded as severe. At discharge from the acute care facility, six patients (33%) were ambulatory with support. At last clinical encounter after a median (range) follow up time of 2.0 years (0.3–6.6 years), the neurological deficit was none/mild in ten patients (59%). Conclusion: For pediatric patients with severe inflammatory neurologic diseases PLEX is a safe treatment option. One third showed early improvement and almost 60% regained independent ambulation over the follow up period.
OP71 - 2706 Autologous hematopoietic stem cell transplantation in pediatric multiple sclerosis: Long-time follow-up K.I. Kirgizov, E.Y. Volkova, E.V. Skorobogatova, S.V. Piliya, A.A. Bologov, R.C. Bembeeva, N.N. Zavadenko. Department of Bone Marrow Transplantation, The Russian Children’s Research Hospital, Moscow, Russia Objective: Autologous hematopoietic stem cell transplantation (Auto-HSCT) is the method of choice for patients with refractory