T. Kalincik
Royal Melbourne Hospital Melbourne MS CentreAuthor Of 3 Presentations
FC04.02 - Effects of natalizumab on patient-reported MS outcomes using prospective data from the Australian MS longitudinal study
Abstract
Background
There is limited evidence on the effects of disease modifying therapies (DMTs) on MS symptoms, health-related quality of life (HRQoL) and employment outcomes, particularly the comparative effectiveness between different available DMTs.
Objectives
By using the prospectively collected patient-reported data in the Australian MS Longitudinal Study (AMSLS) from 2015 to 2017, we aimed to compare natalizumab to other DMTs in relation to employment outcomes, MS symptom severity, HRQoL, and progression in the previous 12 months.
Methods
Medication and Disease Course surveys were conducted in 2015, 2016 and 2017, and collected data on DMTs, severity of 13 MS symptoms (0-10 scale), disability, HRQoL by European Quality of Life with five dimensions (EQ-5D) and work productivity loss (absenteeism, presenteeism, total work productivity loss in the previous 4 weeks). We used marginal structural models to estimate causal effect of natalizumab versus other DMT comparators (any other DMT, classic injectables, oral therapies (teriflunomide and dimethyl fumarate), higher efficacy DMTs (fingolimod, alemtuzumab and mitoxantrone), fingolimod, and alemtuzumab), while adjusting for time-varying confounders and intermediates of treatment effects.
Results
The analysis included 2836 observations. Compared to any other DMTs, natalizumab was associated with superior effects over time on improving balance, vision symptoms, sensory symptoms, bladder symptoms, sexual dysfunction, and feelings of anxiety. The strongest effect was seen for improving sensory problems (mean coefficient -0.44 (-0.66 to -0.22) per year). There was no evidence of an effect of natalizumab over time on improving HRQoL measured by the EQ-5D, but use of any other DMTs were associated with a significant decrease in EQ-5D. The use of natalizumab was associated with a marginal decrease in self-reported progression in the previous 12 months while the use of injectable DMTs and fingolimod were associated with an increased self-reported progression. The use of natalizumab was associated with a reduction in work productivity loss due to absenteeism compared to a worsening for any other DMT, and similar trends were less pronounced for presenteeism and total work productivity loss.
Conclusions
Compared to other DMTs, the use of natalizumab was associated with superior effects over time for several MS symptoms and absenteeism.
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.
SS02.04 - First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes
- S. Simpson-Yap
- E. De Brouwer
- T. Kalincik
- N. Rijke
- J. Hillert
- C. Walton
- G. Edan
- Y. Moreau
- T. Spelman
- L. Geys
- T. Parciak
- C. Gautrais
- N. Lazovski
- A. Pirmani
- A. Ardeshirdavani
- L. Forsberg
- A. Glaser
- R. McBurney
- H. Schmidt
- A. Bergmann
- S. Braune
- A. Stahmann
- R. Middleton
- A. Salter
- A. Van Der Walt
- J. Rojas
- I. Van Der Mei
- R. Ivanov
- G. Sciascia Do Olival
- A. Dias
- M. Magyari
- D. Brum
- M. Mendes
- R. Alonso
- R. Nicholas
- J. Bauer
- A. Chertcoff
- A. Zabalza
- G. Arrambide
- G. Comi
- L. Peeters
Abstract
Background
As the COVID-19 pandemic amplifies, efforts to minimise the risk on vulnerable people are essential. People with multiple sclerosis (MS) may be a vulnerable group due to the high proportion taking long-term immunosuppressive disease-modifying therapies (DMTs). Studies from Italy and France suggest older age, higher disability and progressive MS are associated with severe COVID-19, yet there remains uncertainty around the influence of DMTs.
Objectives
Given the many approved MS DMTs and the relatively low frequency of COVID-19 in MS patients per country, international data sharing is desirable to examine the impact of DMTs on COVID-19 severity. Here, we present the first results of the COVID-19 in MS global data sharing initiative of the MS International Federation and MS Data Alliance and many other data partners to inform MS clinical management during the COVID-19 pandemic.
Methods
Clinician-reported data from 21 countries were aggregated into a dataset of 1540 patients. Characteristics of admission to hospital, admission to intensive care unit (ICU), need for artificial ventilation, and death, were assessed in patients with confirmed or suspected COVID-19 infection using log-binomial regression. Adjusted prevalence ratios (aPR) were calculated adjusting for age, sex, MS type, and Expanded Disability Status Scale (EDSS).
Results
Of 1540 patients, 476 (30.9%) with suspected and 776 (50.4%) with confirmed COVID-19 were included in the analysis. Older age, progressive MS and higher EDSS were associated with higher frequencies of severe outcomes. Anti-CD20 DMTs, ocrelizumab and rituximab, were positively associated with hospital admission (aPRs=1.19 & 1.58), ICU admission (aPRs=3.53 & 4.12), and the need for artificial ventilation (aPRs=3.17 & 7.27) compared to dimethyl fumarate. Higher frequencies of all three outcomes were associated with combined anti-CD20 DMT use compared to all other DMTs (hospitalisation aPR=1.49; ICU aPR=2.55; ventilation aPR=3.05) and compared to natalizumab (hospitalisation aPR=1.99; ICU aPR=2.39; ventilation aPR=2.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases and upon exclusion of each contributing data source in turn. No associations were observed between DMTs and death.
Conclusions
This study used the largest federated international cohort of people with MS and COVID19 currently available. We demonstrate a consistent association of anti-CD20 DMTs with hospitalisation, ICU admission and use of artificial ventilation suggesting their use among MS patients at risk for COVID-19 exposure may be a risk factor for more severe COVID-19 disease. To address study limitations, further research incorporating comorbidities, smoking and body mass index is required. Alternative study designs are needed to address questions on COVID-19 susceptibility among people with MS.