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 1 Presentation
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.
Presenter Of 1 Presentation
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.