Author Of 3 Presentations
P0137 - Prognostic value of NK/T ratios for disease activity in multiple sclerosis (ID 1122)
Abstract
Background
BACKGROUND: Experimental, genetic and therapeutic studies suggest a role for natural killer (NK) cells in multiple sclerosis (MS). A study analysing the re-emergence of Th17 cells after autologous hematopoietic stem cell transplantation proposes that the relative presence of NK cells compared to CD4+ T cells is beneficial in MS, as it is associated with lower levels of Th17. As such, they propose that NK/T cell ratios may be used as a biomarker for therapeutic effect of stem cell transplantation. This ratio has not been investigated in the context of clinical outcome. Additionally, the subsets of NK cells and T cells have not been investigated in regards to this NK/T cell ratio.
Objectives
OBJECTIVES: To explore the relevance of NK cell / CD4+ T cell ratios in a cohort of MS patients treated with interferon beta by analysing NK cell subsets and T cell subsets. Additionally, to find the prognostic value of these ratios for disease activity in MS
Methods
METHODS: Baseline peripheral blood mononuclear cells of 50 relapsing remitting MS patients, participating in our vitamin D supplementation study (the SOLARIUM study), were isolated and analysed with flow cytometry for NK and T cell subsets. MS disease activity was quantified by assessment of the occurrence of new MRI-lesions, relapses, and by measuring mean plasma neurofilament light chain (NfL) levels at baseline and after 48 weeks follow-up.
Results
RESULTS: The proportion of NK cells correlated negatively with CD4+ T cells [R=-0.335 p=0.001] and IL17-A+CD4+ T cells [R=-0.203 p=0.043], which was mainly driven by the CD56bright subset. Participants with MRI activity or relapses at 48 weeks follow-up displayed lower NK/ IL-17A+ CD4+ T cell ratios [p=0.025 and p=0.006, respectively]. The NK / IL-17A+CD4+ T cell ratio correlated negatively with NfL levels [R=-0.320 p=0.050]. Vitamin D supplementation did not affect these ratios.
Conclusions
CONCLUSIONS: Our data suggests a protective role of a relatively expanded NK cell compartment compared to the CD4+ T cell subset fractions in interferon beta-treated RRMS patients. Further research is required to confirm the use of the NK cell/CD4+ T cell ratio as prognostic biomarker for disease activity in MS.
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
P0876 - High and low efficacy therapy in secondary progressive multiple sclerosis after accounting for therapeutic lag. (ID 760)
Abstract
Background
In secondary progressive multiple sclerosis (SPMS), reduction in the rates of disability accrual after starting disease modifying therapy (DMT) has largely been limited to patients with ongoing inflammatory activity. A delayed treatment effect, termed therapeutic lag, may obscure therapeutic benefits in SPMS.
Objectives
To compare the effect of high and low efficacy DMT on disability outcomes in patients with recently active and inactive SPMS after accounting for therapeutic lag.
Methods
Using data from MSBase, a multinational MS registry, and OFSEP, the French MS registry, we identified patients with SPMS as per a previously validated objective definition. We identified patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferons, glatiramer acetate, teriflunomide) DMT after SPMS onset. Based on our previous work, an individualised estimate of duration of therapeutic lag was calculated for each patient. Only events that occurred after the estimated therapeutic lag period were included in the analysis. Propensity score matching was used to select groups with comparable baseline characteristics. Disability and relapse outcomes were compared in paired, pairwise-censored analyses adjusted for visit density.
Results
Of 7359 patients with SPMS, 1000 patients fulfilled the criteria for study inclusion (510 active SPMS, 490 inactive SPMS). For the relapse outcomes, patients with active SPMS treated with high-efficacy DMTs experienced lower probabilities of relapses than low-efficacy DMTs (hazard ratio [HR] 0.7 [95%CI 0.5-0.9], p=0.006). Patients with inactive SPMS had similar probabilities of relapses in the high and low efficacy DMT groups (0.8 [0.6-1.2], p=0.39). No difference in the risk of 6-month sustained disability accumulation, or proportion of patients reaching EDSS>=7, was observed between groups when accounting for therapeutic lag.
Conclusions
The risk of disability accumulation in SPMS seems to be comparable in patients treated with high- and low- efficacy DMT. High efficacy DMT is superior to low efficacy therapy in reducing relapse activity in patients with active SPMS, but not those with inactive SPMS. Pre-treatment inflammatory activity, clinical or radiological, is a treatable target in SPMS which may benefit from higher-efficacy anti-inflammatory therapies.