Author Of 1 Presentation
PS12.04 - Pregnancy in a modern day multiple sclerosis cohort: Predictors of relapse during pregnancy
- W. Yeh
- P. Widyastuti
- A. Van Der Walt
- J. Stankovich
- M. Gresle
- E. Havrdova
- D. Horakova
- K. Vodehnalova
- S. Ozakbas
- S. Eichau
- P. Duquette
- T. Kalincik
- F. Patti
- C. Boz
- M. Terzi
- B. Yamout
- J. Lechner-Scott
- P. Sola
- O. Skibina
- M. Barnett
- M. Onofrj
- M. Sá
- P. McCombe
- P. Grammond
- R. Ampapa
- F. Grand'Maison
- R. Bergamaschi
- D. Spitaleri
- V. Van Pesch
- E. Cartechini
- S. Hodgkinson
- A. Soysal
- A. Saiz
- T. Uher
- D. Maimone
- R. Turkoglu
- R. Hupperts
- M. Amato
- F. Granella
- C. Oreja-Guevara
- A. Altintas
- R. Macdonell
- T. Castillo-Trivino
- H. Butzkueven
- R. Alroughani
- V. Jokubaitis
- T. Study Group
Abstract
Background
Historically, disease activity diminished during pregnancy in women with relapsing-remitting MS. Today, women with high disease activity are more likely to attempt pregnancy due to the disease control that new therapies offer. But disease activity during pregnancy in the modern day remains understudied.
Objectives
Describe disease activity in a modern pregnancy cohort, grouped by preconception disease-modifying therapy (DMT) class; determine the predictors of relapse during pregnancy.
Methods
Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included. DMT were classed by low, moderate and high-efficacy. Annualized relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of relapse during pregnancy were determined using clustered logistic regression.
Results
We included 1640 pregnancies from 1452 women. DMT used in the year before conception were none (n=346), low (n=845), moderate (n=207) and high-efficacy (n=242). Most common DMT in each class was interferon-beta (n=597), fingolimod (n=147) and natalizumab (n=219) for low, moderate and high-efficacy respectively. Conception EDSS ≥2 was more common in higher efficacy DMT groups (high: 41.3%; moderate 28.5%; low 22.4%; none 20.2%). For low-efficacy and no DMT groups, ARR fell through pregnancy. ARR of the moderate-efficacy group increased in the 1st pregnancy trimester (0.55 [95% CI 0.36-0.80] vs 0.14 [95% CI 0.10-0.21] on low-efficacy), then decreased to a trough in the third. Conversely, ARR steadily increased throughout pregnancy for those on high-efficacy DMT (3rd trimester: 0.42 [95% CI 0.25-0.66] vs 0.12 [95% CI 0.07-0.19] on low-efficacy). Higher efficacy DMT groups were associated with higher ARR in the early postpartum period (high: 0.84 [95% CI 0.62-1.1]; moderate: 0.90 [95% CI 0.65-1.2]; low: 0.47 [95% CI 0.38-0.58]). Preconception use of high and moderate-efficacy DMT and higher preconception ARR were predictors of relapse in pregnancy. But, continuation of high-efficacy DMT into pregnancy was protective against relapse (odds ratio 0.80 [95% CI 0.68-0.94]). Age ≥35 years was associated with reduced odds of relapse.
Conclusions
Women with RRMS treated with moderate or high-efficacy DMT are at greater risk of relapse during pregnancy. Careful pregnancy management, and use of long-acting high-efficacy DMT preconception, or continuing natalizumab into pregnancy, may prevent relapse in pregnancy.
Author Of 2 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.
P1131 - Pregnancy in a modern day multiple sclerosis cohort: Predictors of postpartum relapse and disability progression (ID 1321)
- W. Yeh
- P. Widyastuti
- J. Stankovich
- M. Gresle
- E. Kubala Havrdová
- D. Horakova
- K. Vodehnalova
- S. Ozakbas
- S. Eichau Madueño
- P. Duquette
- T. Kalincik
- F. Patti
- C. Boz
- M. Terzi
- B. Yamout
- J. Lechner-Scott
- P. Sola
- O. Skibina
- M. Barnett, Md
- M. Onofrj
- M. Sá
- P. McCombe
- P. Grammond
- R. Ampapa
- F. Grand'Maison
- R. Bergamaschi
- D. Spitaleri
- V. Van Pesch
- E. Cartechini
- S. Hodgkinson
- A. Soysal
- A. Saiz
- T. Uher
- D. Maimone
- R. Turkoglu
- R. Hupperts
- M. Amato
- F. Granella
- C. Oreja-Guevara
- A. Altintas
- R. Macdonell
- T. Castillo-Trivino
- H. Butzkueven
- R. Alroughani
- A. Van Der Walt
- T. Msbase Study Group
Abstract
Background
Disease activity has been investigated in pregnant women with RRMS treated with low-efficacy or no therapy. How newer, more efficacious therapies affect relapse and disability progression risk after pregnancy remains understudied.
Objectives
To describe disease activity in a modern pregnancy cohort contrasted with historical cohorts. To determine the predictors of postpartum relapse and the predictors of six-month confirmed disability progression events in a contemporary pregnancy cohort.
Methods
Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 (modern cohort) were compared with those conceived between 2005-2010 and pre-2005. Annualised relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of time-to-relapse postpartum (1st 3 months) and time to 6-month confirmed disability progression event were determined with clustered Cox regression analyses. Breastfeeding duration and time to DMT reinitiation were modelled as time-varying covariates.
Results
We included 1640 pregnancies from 1452 women (modern cohort). Disease-modifying therapy (DMT) used in the year before conception included interferon-beta (n=597), natalizumab (n=219) and fingolimod (n=147). Continuation of DMT up to conception increased over time (31% pre-2005 vs 54% modern cohort). Preconception ARR decreased across epochs (pre-2005: 0·58 [95% CI 0·49-0·70]; 2005-2010: 0·40 [95% CI 0·36-0·45]; modern: 0·29 [95% CI 0·27-0·32]). In all epochs, ARR decreased during pregnancy to reach similar troughs in the 3rd trimester, and rebounded in the 1st 3-months postpartum. Preconception use of high-efficacy DMT predicted early postpartum relapse (hazard ratio (HR) 2.1 [1.4-3.1]); although those on no DMT were also at risk of postpartum relapse, relative to women on low-efficacy DMT (HR 2.7 [1.2-5.9]). Conception EDSS ≥2, higher preconception and in-pregnancy ARR were also risk factors. DMT reinitiation, particularly of high-efficacy DMT (HR 0.17 [0.07-0.38]), was protective against postpartum relapse. Women who breastfed were less likely to relapse (HR 0.63 [0.42-0.94]). 4.5% of modern pregnancies had confirmed disability progression after delivery. This was predicted by higher pregnancy and postpartum ARR, with postpartum ARR remaining independently predictive in multivariable analysis (HR 1.5 [1.2-2.0]).
Conclusions
The early postpartum period remains a period of vulnerability for disease rebound in women with MS in the modern era. Early DMT reinitiation, particularly with high-efficacy treatment, is protective against postpartum relapse. Confirmed disability progression events after pregnnacy are uncommon in the modern era. Relapse activity is the key driver of these events.