Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

2020 ◽  
pp. 135245852097821
Author(s):  
Sandra Vukusic ◽  
Iuliana Ionescu ◽  
Catherine Cornu ◽  
Nadine Bossard ◽  
Françoise Durand-Dubief ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Treatment Effect ◽  
Sex Steroids ◽  
Post Partum ◽  
Proof Of Concept ◽  
Nomegestrol Acetate ◽  
Annualized Relapse Rate ◽  
Transdermal Estradiol ◽  
In Pregnancy

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.

BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS

2020 ◽  
pp. 135245852096914
Author(s):  
Mikael Cohen ◽  
Lydiane Mondot ◽  
Florence Bucciarelli ◽  
Béatrice Pignolet ◽  
David-Axel Laplaud ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prospective Study ◽  
Relapse Rate ◽  
Group Versus ◽  
Lower Probability ◽  
Highly Active ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Magnetic Resonance Imaging Mri ◽  
A Prospective Study

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.

Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis

2007 ◽  
Vol 13 (8) ◽  
pp. 975-980 ◽  
Author(s):  
E. Cocco ◽  
P. Marchi ◽  
C. Sardu ◽  
P. Russo ◽  
A. Paolillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Relapse Rate ◽  
Serious Adverse Events ◽  
T2 Lesions ◽  
End Of Treatment ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Relapsing Remitting Multiple Sclerosis

We investigated the clinical and MRI effects of mitoxantrone (MITOX) administered to 45 patients during the first five years of highly active relapsing-remitting multiple sclerosis. Differences occurring between the end of treatment and follow-up (clinical mean: 3.6 years; brain MR: 1.8 years) with respect to baseline variables (EDSS, annualized relapse rate, active T2 lesions, new T1 lesions and number of Gd-enhancing lesions) were analysed using parametric and non-parametric tests. One patient developed leukemia four months after the end of the treatment; no other serious adverse events occurred during treatment and the follow-up period. A clinically relevant reduction in the annualized relapse rate ( P < 0.0001 at end of treatment and P < 0.0001 at follow-up) and improvement in the EDSS ( P < 0.0001 at end of treatment and P = 0.0005 at follow-up) was found. At the end of treatment, 53% of patients experienced no increase in active T2 lesions, while 73% showed no increase in the number of new T1 lesions. At follow-up, 41 out of 45 (91%) patients showed a stable MRI pattern and were active-scan free. Despite potential serious adverse events, MITOX may be considered an option in selected patients with very active early MS. Multiple Sclerosis 2007; 13: 975—980. http://msj.sagepub.com

scholarly journals Women’s Health: Contemporary Management of MS in Pregnancy and Post-Partum

Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 32 ◽  
Author(s):  
Kelly Tisovic ◽  
Lilyana Amezcua
Keyword(s):  
Multiple Sclerosis ◽  
Post Partum ◽  
Fetal Exposure ◽  
Childbearing Age ◽  
Maternal Complications ◽  
Increased Risk ◽  
Effective Contraception ◽  
Disease Modifying ◽  
Contemporary Management ◽  
In Pregnancy

Multiple sclerosis (MS) primarily affects women in childbearing age and is associated with an increased risk of adverse post-partum outcomes. Relapses and now fetal exposure to disease modifying treatments in the early phase of pregnancy and thereafter are of concern. Safe and effective contraception is required for women who wish to delay or avoid pregnancy while on disease-modifying treatments. Counseling and planning is essential to assess the risk of both fetal and maternal complications, particularly now in the era of highly efficient and riskier therapies. The purpose of this review is to provide a practical framework using the available data surrounding pregnancy in MS with the goal of optimizing outcomes during this phase in MS.

Course of relapsing–remitting multiple sclerosis before, during and after natalizumab

2010 ◽  
Vol 17 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Michael D Kaufman ◽  
R Lee ◽  
HJ Norton
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Relapse Rate ◽  
Generalized Estimating Equations ◽  
Chart Review ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 ( p = 0.0003) during the prior 12 months and to 0.35 ( p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder

2016 ◽  
Vol 22 (11) ◽  
pp. 1413-1420 ◽  
Author(s):  
Yuko Shimizu ◽  
Kazuo Fujihara ◽  
Takashi Ohashi ◽  
Ichiro Nakashima ◽  
Kazumasa Yokoyama ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Low Doses ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Annualized Relapse Rate ◽  
Antibody Positivity ◽  
Aqp4 Antibody

Background: Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). Objective: To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. Methods: We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. Results: Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. Conclusion: In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

scholarly journals Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Sun ◽  
Yanbo Yang ◽  
Zilan Wang ◽  
Fan Jiang ◽  
Zhouqing Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Adverse Events ◽  
Treatment Period ◽  
Relapse Rate ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate

Background: Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P3 receptor activation.Methods: e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes.Results: 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, −0.10 [95% CI, −0.15, −0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, −0.20 [95% CI, −0.34, −0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, −1.12 [95% CI, −1.52, −0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77–1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83–2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found.Conclusions: Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.

Clinical characteristics of progressive relapsing multiple sclerosis

2004 ◽  
Vol 10 (4) ◽  
pp. 451-454 ◽  
Author(s):  
M J Tullman ◽  
R J Oshinsky ◽  
F D Lublin ◽  
G R Cutter
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Clinical Characteristics ◽  
Age At Onset ◽  
Retrospective Chart Review ◽  
Disability Status ◽  
Acute Exacerbations ◽  
Annualized Relapse Rate ◽  
The Mean ◽  
Relapsing Multiple Sclerosis

Objective: Patients with progressive relapsing (PR) multiple sclerosis (MS) may accrue disability by incomplete recovery from acute exacerbations and by ongoing deterioration. In primary progressive (PP) MS, disability accumulates solely by continuous decline. Because it is the least common form of MS, there is scant information regarding the clinical characteristics of PRMS, but relapses are reportedly uncommon. The purpose of this study is to describe the clinical features of a cohort of patients with PRMS. Methods: A retrospective chart review of 16 patients diagnosed with PRMS at two academic MS centres over a four-year period. Results: Nine men and seven women had PRMS. The mean age at onset was 35.19/11.2 years. The most common presenting symptom was a progressive myelopathy. The mean disease duration was 10.19/8.5 years and the average time to first exacerbation was 4.19/3.7 years. Patients had an average of 2.89/2.3 relapses with an annualized relapse rate of 0.69/0.8. Time to Expanded Disability Status Scale (EDSS) 6.0 was strongly associated with time to first exacerbation. Although there was no correlation between the number of relapses and time to EDSS 6.0, there was a modest inverse relation between time to EDSS 6.0 and annualized relapse rate. Conclusions: Relapses in PRMS may occur more often than previously described and disability may accumulate more rapidly in PRMS than in PPMS. We suggest differentiating between these two forms of MS.

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