Author Of 3 Presentations
P0636 - Relationship of real-world brain atrophy to MS disability using icobrain: 4 centre pilot study (ID 716)
- A. Nguyen
- D. Horakova
- E. Havrdova
- M. Barnett
- M. Sormani
- E. Lui
- F. Gaillard
- P. Desmond
- H. Prime
- M. Datta
- A. Van Der Walt
- V. Jokubaitis
- B. Weinstock-Guttman
- M. D’hooghe
- G. Nagels
- V. Van Pesch
- G. Laureys
- L. Van Hijfte
- J. Lechner-Scott
- F. Patti
- E. Cristiano
- J. Rojas
- D. Sima
- W. Van Hecke
- T. Kalincik
- H. Butzkueven
Abstract
Background
To date, no studies have explored the relationship between brain atrophy and MS disability using differing MRI protocols and scanners at multiple sites.
Objectives
To assess the association between brain atrophy and MS disability, as measured by EDSS and 6-month confirmed disability progression (CDP).
Methods
In this retrospective study at 4 MS centres, a total of 1300 patients had brain MRI imaging assessed by icobrain. Relapse-onset MS patients were included if they had two clinical MRIs 12 (±3) months apart and ≥2 EDSS scores post MRI-2, the first ≤3 months from MRI-2, with ≥6 months between first and last EDSS. Volumetric data were analysed if the alignment similarity between two images was as good as that of same-scanner scan-rescan images (normalised mutual information ≥0.2). The percentage brain volume change (PBVC), percentage grey matter change (PGMC), FLAIR lesion volume change, whole brain volume, grey matter volume, FLAIR lesion volume and T1 hypointense lesion volume at MRI-2 were calculated. Ordinal mixed effect models were used to determine the association between these volumetric MRI measures and all EDSS scores post MRI-2. Cox proportional hazards models were used for the 6-month CDP outcome, using a subset of patients with ≥3 EDSS. Models were adjusted for proportion of time spent on disease-modifying therapy during MRIs ± whole brain/grey matter volume at baseline MRI.
Results
Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. During the follow-up period (median 3.8 years, range 1.3-8.9), 29 of 244 (12%) patients experienced 6-month CDP. There was no evidence for association between annualised PBVC or PGMC and CDP or EDSS (p>0.05). Cross-sectional whole brain and grey matter volume (at MRI-2) tended to associate with CDP (HR 0.99, 95% CI 0.98-1.00, p=0.06). Every 1ml of whole brain or grey matter volume lost represented a 1% higher chance of reaching 6-month CDP. Only whole brain volume (at MRI-2) was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the slope of EDSS change over time (β -0.001, SE 0.0003, p=0.02). On average, every 33ml reduction of brain volume was associated with a 1 step increase in EDSS.
Conclusions
In this real-world clinical setting where a fifth of the brain atrophy analysis were performed on different scanners, we found no association between individual brain atrophy and MS disability. However, there was an association between cross-sectional whole brain volume with EDSS and slope of EDSS change.
P0862 - Disability accrual in primary-progressive & secondary-progressive multiple sclerosis (ID 1232)
- S. Harding-Forrester
- I. Roos
- S. Sharmin
- I. Diouf
- C. Malpas
- A. Nguyen
- N. Moradi
- D. Horáková
- E. Kubala Havrdová
- F. Patti
- G. Izquierdo
- S. Eichau
- A. Prat
- M. Girard
- P. Duquette
- M. Onofrj
- A. Lugaresi
- F. Grand'Maison
- B. Weinstock-Guttman
- M. Amato
- P. Grammond
- O. Gerlach
- S. Ozakbas
- P. Sola
- D. Ferraro
- H. Butzkueven
- J. Lechner-Scott
- C. Boz
- R. Alroughani
- V. Van Pesch
- E. Cartechini
- M. Terzi
- D. Maimone
- C. Ramo-Tello
- D. Spitaleri
- L. Kappos
- B. Yamout
- M. Sá
- M. Slee
- Y. Blanco
- R. Bergamaschi
- E. Butler
- G. Iuliano
- F. Granella
- Y. Sidhom
- R. Gouider
- R. Ampapa
- B. Van Wijmeersch
- R. Karabudak
- J. Prevost
- J. Sánchez-Menoyo
- F. Verheul
- P. McCombe
- T. Castillo-Triviño
- R. Macdonell
- A. Altintas
- G. Laureys
- L. Van Hijfte
- A. Van Der Walt
- S. Vucic
- R. Turkoglu
- M. Barnett
- E. Cristiano
- M. Zakaria
- V. Shaygannejad
- S. Hodgkinson
- A. Soysal
- T. Kalincik
Abstract
Background
Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS.
Objectives
We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016).
Methods
Inclusion required adult-onset progressive MS; ≥ 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS ≤ 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if ≥ 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over ≥ 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS ≥ 7 (wheelchair required) was assessed (Kaplan-Meier).
Results
5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 ± 10.2, vs. 41.5 ± 10.7 [mean ± SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78–0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98–0.99); and higher in males (1.18; 1.12–1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71–0.87) but similar for PPMS-A (1.01; 0.93–1.10) and SPMS-N (0.94; 0.85–1.05). Sensitivity analyses corroborated these results. However, patients with SPMS-A reached EDSS ≥ 7 at younger ages (cumulative probability 30% by 57, vs. 64–66 for SPMS-N, PPMS-A, PPMS-N).
Conclusions
Progressive phase onset is later in SPMS than PPMS. Hazard of disability accrual during the progressive phase is lower in SPMS than PPMS. However, patients with SPMS-A reach wheelchair requirement younger than other progressive phenotypes, reflecting earlier progression onset versus SPMS-N, and greater disability at onset versus PPMS
P1066 - Treatment satisfaction in patients with highly-active relapsing multiple sclerosis treated with cladribine tablets: CLARIFY-MS study interim analysis (ID 968)
Abstract
Background
Multiple sclerosis (MS), a chronic disabling disease requiring long-term treatment and regular monitoring, is associated with negative effects on health-related quality of life (HRQoL). CLARIFY-MS (NCT03369665) aims to assess the impact of cladribine tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years; CT3.5) on HRQoL and treatment satisfaction in patients with highly-active relapsing MS (RMS).
Objectives
To present an interim analysis of CLARIFY-MS at 6 months after initiating treatment with CT, assessing treatment satisfaction through the Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 and safety through the collection of safety assessments in highly-active RMS patients.
Methods
CLARIFY-MS is an ongoing phase IV, open label, single arm, multicenter, 2-year study. Patients with RMS received CT3.5, with 2 weeks of active treatment per course (week 1 and 5 of each year). TSQM v1.4 was used to assess patient-reported treatment satisfaction (a score of 100 is the best possible rating). The TSQM measures 14 items across four domains: effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items).Treatment-emergent adverse events (TEAEs), serious adverse events (AEs), and lymphocyte counts were recorded.
Results
Treatment satisfaction: Of 554 patients screened, 482 received CT. The age and Expanded Disability Status Scale adjusted global treatment satisfaction score (95% confidence interval) at Month 6 was 70.0 (66.6–73.5). Treatment-experienced patients (prior treatment with disease-modifying drugs [DMDs]) reported similar treatment satisfaction scores to DMD-naïve patients (70.2 vs 68.7). At Month 6, >75% of patients rated the TSQM side effects score with 100. The mean side effects score was 91.9, mean convenience 86.6. Safety: 275 patients (57.1%) experienced ≥1 TEAE after drug initiation, most commonly headache and lymphopenia. Most post-baseline lymphopenias were of grade 1-2; 33 patients (6.8%) experienced grade 3 lymphopenia and no grade 4 lymphopenia was observed.
Conclusions
This interim analysis of CLARIFY-MS found that at 6 months, patients were generally satisfied with CT treatment. The convenience of CT treatment and side effect profile were especially important to patients. Safety results at 6 months post-treatment are consistent with the known safety profile, with no new emerging safety signal; most lymphopenias were grade 1-2.