Author Of 4 Presentations
P0278 - A Systematic Review and Meta-analyses of Pregnancy and Fetal Outcomes in Women with Multiple Sclerosis. IMI2 ConcePTION (ID 358)
Abstract
Background
Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited.
Objectives
The aim of this systematic review and meta-analysis was to evaluate pregnancy outcomes in women with MS treated with DMDs.
Methods
The term “multiple sclerosis” combined with DMDs and pregnancy terms were searched in Embase and Medline databases to identify studies published between Jan 2000 and Jul 2019. Only studies in which the exposure occurred in utero and compared patients exposed to a DMD versus MS patients without treatment were included, regardless of the study design. 1260 studies were identified, and ten studies met our inclusion criteria. MS treated patients were analysed overall and stratified by DMDs class and by type. Pooled relative risk (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed was calculated using a random effects model.
Results
Overall, for MS patients exposed to DMDs the RR (95% confidence interval) for spontaneous abortion was 1.14, (0.99-1.32), for preterm births 0.93 (0.72-1.21) and for major congenital malformations (MCM) in live births 0.86 (0.47-1.56) when compared to MS without treatment. The pooled prevalences of each pregnancy outcome in MS patients exposed to any DMD were: spontaneous abortions 11.6% (7.4-16.7), premature births 12.1% (9.0-15.6) and MCM 3.0% (1.8-4.4). The most common major congenital malformations reported in MS patients exposed to DMDs were atrial septal defect (ASD) (N=4), polydactyly (N=4) and club foot (N=3), which are among the most prevalent birth defects observed in the general population. Each case of ASD was present in patients exposed to different drugs (natalizumab, beta-interferon, glatiramer acetate and mitoxantrone).
Conclusions
Interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, preterm births or MCM. Future studies that assess the effect of individual DMDs are needed to enable decisions on the best treatment options.
P0320 - Effect of age on effectiveness and discontinuation of subcutaneous interferon beta-1a, and healthcare utilization, in patients with multiple sclerosis (ID 391)
Abstract
Background
Subcutaneous interferon beta-1a (sc IFNβ-1a) is a well-established multiple sclerosis (MS) therapy with cumulative exposure of approximately 1,766,525 patient-years. Previous clinical trials demonstrate that patient age does not impact the efficacy of such therapy for treatment of MS.
Objectives
Using real-world data, we evaluated the effect of age on the effectiveness and discontinuation of sc IFNβ-1a, and healthcare utilization, in patients with MS.
Methods
This cohort study using MarketScan© Databases included adult patients with MS newly initiated with sc IFNß-1a between Jul2010-Dec2015, with at least 6 months’ patient history before initiation (index date), and a recorded diagnosis of MS over the 6 months before or at initiation. Follow-up was until end of study period, end of insurance, or treatment discontinuation. Incidence rate (IR) per 100 person-years was used for discontinuation. Hazard ratio (HR) and 95% confidence internal (CI) were used to compare time to first relapse and discontinuation.
Results
Among 5,340 patients included, 14.5% were aged 18-30y, 27.5% 31-40y, 30.5% 41-50y, and 27.5% were 51+y. Relapse-free probability at 2-y ranged from 91.44% in 18-30y to 92.82% in 51+y. Compared with 18-30y, the HRs for relapse at 2-y (95%CI) were 31-40y: 1.00 (0.70, 1.43), 41-50y: 0.79 (0.55, 1.12), and 51+y: 0.86 (0.60, 1.24). In all age groups, hospitalizations due to MS were ≤0.01 and neurology visits were 0.2 patient per-month (PPM) over 2-y. Mean number (95%CI) of magnetic resonance imaging (MRI) scans performed PPM over 2-y ranged from 0.25 (0.16, 0.34) in 18-30y to 0.14 (0.12, 0.16) in 51y+ and outpatients visits due to MS from 0.68 (0.57, 0.78) to 0.75 (0.67, 0.82). Discontinuation IR at 2-y was 72.06 (65.12, 79.52) in 18-30y and 57.95 (53.76, 62.38) in 51+y. Compared to 18-30y, the HR of discontinuation decreased from 0.89 (0.79, 1.01) in 31-40y to 0.86 (0.76, 0.97) in 51+y.
Conclusions
Data suggest no effect of age on the effectiveness of sc IFNß-1a in the real-world setting, while treatment discontinuation decreased with increasing age. Older MS patients initiating sc IFNß-1a appear to have less active disease, reflected in lower relapses, and undergo MRI scanning less frequently than younger patients.
P0470 - Initial findings from a dynamic cohort study of patients with multiple sclerosis: A proactive approach for safety and comparative effectiveness (ID 465)
Abstract
Background
A dynamic cohort (DC) study is a non-interventional, longitudinal study – based on healthcare claims data – that utilizes an open, cohort design to allow for new patients to enter over time and for additional follow-up to be accrued. In the setting of multiple sclerosis (MS), a DC study therefore allows for study of the natural history of disease, rates of pre-defined adverse events, relapses, and healthcare utilization, including the changing disease-modifying drug (DMD) landscape. Furthermore, ad hoc queries for new research questions can be rapidly implemented.
Objectives
To describe initial patient characteristics and treatment utilization in a DC study of patients with MS from the US MarketScan® Research Database.
Methods
Eligible patients (aged ≥18 years) had a database history of >1 year and were followed from the time of MS diagnosis through death, loss of enrollment coverage, or end of the current study period (2011 to 2017; annual data updates will continue until 2023). Cohorts of patients treated with DMDs, stratified by new users or switchers, were from the date of the first DMD prescription. Analysis of DMD usage patterns was limited to interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, alemtuzumab, natalizumab, and ocrelizumab.
Results
Overall, 77,015 patients with MS (median age 50 years, 76% female) were observed in the initial study period, of whom 27,988 were new (incident) MS patients. Among all MS patients, 49,964 (65%) used a DMD at any point in the study period. There were 12,647 new users of dimethyl fumarate, 8,195 of interferon beta-1a, 8,120 of natalizumab, 7,535 of fingolimod, 478 of alemtuzumab, and 292 of ocrelizumab; a majority had a prior history of treatment with interferons, glatiramer acetate, or daclizumab, and had received steroids in the previous year.
Conclusions
This DC study for MS is a key design for a proactive and expedited approach for continuous post-marketing safety and effectiveness monitoring of DMDs. Initial findings show that a large proportion of MS patients (35%) are not treated with a DMDs in the US. As additional data become available on an annual basis, with new MS patients added to the growing cumulative cohort, this study will continue to provide relevant information on the natural history of MS and its management with DMDs.
P0880 - Low discontinuation rate and side-effect burden after switching to cladribine tablets: Canadian experience from the adveva® patient support program (ID 1083)
Abstract
Background
Cladribine tablets were approved in Canada in November 2017. All patients prescribed cladribine tablets in Canada are enrolled upon their consent in the adveva patient support program (PSP), which provides drug education, assistance with reimbursement and patient support services.
Objectives
To examine the demographics and treatment history of patients initiating cladribine tablets in Canada, assess the discontinuation rate over the two-year treatment and describe reported adverse events (AEs).
Methods
Analysis of data routinely collected by adveva nurses and all reported AEs from Dec2017 to Jan2020. Patients were included if they consented to enroll in the adveva PSP. They were contacted at enrollment and periodically therafter. Follow-up stopped when treatment was completed/discontinued.
Results
Overall, 1864 patients enrolled in the program; 1373 were female (74.4%) and mean age was 41.54 years (standard deviation [SD]: 10.34). None of the patients were treatment naïve; most (n=1191; 63.9%) had received only one prior disease modifying drug (DMD). The most recent prior DMDs were glatiramer acetate (23.1%), dimethyl fumarate (20.4%), teriflunomide (16.5%), fingolimod (10.9%), and subcutaneous interferon beta-1a (10.4%). Of 1864 enrolled, 1679 (90.1%) had completed pre-treatment evaluation. Of those, 1415 (84.3%) started year-1. Among those, 483 (34.1%) started year-2 and 394 (27.8%) completed it. Mean time to year-2 initiation was 12.75 (SD: 1.27) months. Among all patients who had started year-1 treatment, 38 (2.69%) reported discontinuation. Among those, 26.3% discontinued within <6 months, 52.6% between 6-12 months and 21.1% at ≥12 months. Main reported reasons were: 28.9% unknown, 21.1% AE other than flu-like syndrome and lymphopenia, 18.4% worsening disease, 10.5% patients decision, and 10.5% family planning/pregnant. A total of 843 patients (59.6%) reported at least one AE. Among the total AEs report (n= 3525)the most frequent were fatigue (8.0%), headache (5.4%), nausea (4.7%), and lymphocytopenia (2.5%).
Conclusions
The Canadian adveva program presented a high enrolment rate. Cladribine tablets were associated with a high continuation rate and most patients successfully self-adminstered the drug. Reported adverse events were not severe.
Presenter Of 2 Presentations
P0278 - A Systematic Review and Meta-analyses of Pregnancy and Fetal Outcomes in Women with Multiple Sclerosis. IMI2 ConcePTION (ID 358)
Abstract
Background
Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited.
Objectives
The aim of this systematic review and meta-analysis was to evaluate pregnancy outcomes in women with MS treated with DMDs.
Methods
The term “multiple sclerosis” combined with DMDs and pregnancy terms were searched in Embase and Medline databases to identify studies published between Jan 2000 and Jul 2019. Only studies in which the exposure occurred in utero and compared patients exposed to a DMD versus MS patients without treatment were included, regardless of the study design. 1260 studies were identified, and ten studies met our inclusion criteria. MS treated patients were analysed overall and stratified by DMDs class and by type. Pooled relative risk (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed was calculated using a random effects model.
Results
Overall, for MS patients exposed to DMDs the RR (95% confidence interval) for spontaneous abortion was 1.14, (0.99-1.32), for preterm births 0.93 (0.72-1.21) and for major congenital malformations (MCM) in live births 0.86 (0.47-1.56) when compared to MS without treatment. The pooled prevalences of each pregnancy outcome in MS patients exposed to any DMD were: spontaneous abortions 11.6% (7.4-16.7), premature births 12.1% (9.0-15.6) and MCM 3.0% (1.8-4.4). The most common major congenital malformations reported in MS patients exposed to DMDs were atrial septal defect (ASD) (N=4), polydactyly (N=4) and club foot (N=3), which are among the most prevalent birth defects observed in the general population. Each case of ASD was present in patients exposed to different drugs (natalizumab, beta-interferon, glatiramer acetate and mitoxantrone).
Conclusions
Interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, preterm births or MCM. Future studies that assess the effect of individual DMDs are needed to enable decisions on the best treatment options.
P0470 - Initial findings from a dynamic cohort study of patients with multiple sclerosis: A proactive approach for safety and comparative effectiveness (ID 465)
Abstract
Background
A dynamic cohort (DC) study is a non-interventional, longitudinal study – based on healthcare claims data – that utilizes an open, cohort design to allow for new patients to enter over time and for additional follow-up to be accrued. In the setting of multiple sclerosis (MS), a DC study therefore allows for study of the natural history of disease, rates of pre-defined adverse events, relapses, and healthcare utilization, including the changing disease-modifying drug (DMD) landscape. Furthermore, ad hoc queries for new research questions can be rapidly implemented.
Objectives
To describe initial patient characteristics and treatment utilization in a DC study of patients with MS from the US MarketScan® Research Database.
Methods
Eligible patients (aged ≥18 years) had a database history of >1 year and were followed from the time of MS diagnosis through death, loss of enrollment coverage, or end of the current study period (2011 to 2017; annual data updates will continue until 2023). Cohorts of patients treated with DMDs, stratified by new users or switchers, were from the date of the first DMD prescription. Analysis of DMD usage patterns was limited to interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, alemtuzumab, natalizumab, and ocrelizumab.
Results
Overall, 77,015 patients with MS (median age 50 years, 76% female) were observed in the initial study period, of whom 27,988 were new (incident) MS patients. Among all MS patients, 49,964 (65%) used a DMD at any point in the study period. There were 12,647 new users of dimethyl fumarate, 8,195 of interferon beta-1a, 8,120 of natalizumab, 7,535 of fingolimod, 478 of alemtuzumab, and 292 of ocrelizumab; a majority had a prior history of treatment with interferons, glatiramer acetate, or daclizumab, and had received steroids in the previous year.
Conclusions
This DC study for MS is a key design for a proactive and expedited approach for continuous post-marketing safety and effectiveness monitoring of DMDs. Initial findings show that a large proportion of MS patients (35%) are not treated with a DMDs in the US. As additional data become available on an annual basis, with new MS patients added to the growing cumulative cohort, this study will continue to provide relevant information on the natural history of MS and its management with DMDs.