Pregnancy

Annette Wundes, MD Co-Director

University of Washington MS Center November 12,2014

Conflicts of Interest

Reports no conflicts pertaining to this

presentation. Research funding: Biogen Idec

Instructional Objectives

Participants will be able to: Discuss the impact of MS on pregnancy Describe the risk of post-partum relapses

Pregnancy Outcomes Overall no adverse pregnancy outcomes

No increase in pregnancy complications

Risk of MS in children: 3-5%

No impact on long-term disability outcomes

Glatiramer acetate Copaxone®

Pregnancy category

B Interferon-beta 1 a/b Avonex®, Rebif®, Betaseron®, Extavia®

C

Natalizumab Tysabri®

C

Fingolimod Gilenya®

C

Terflunimide Aubagio®

X

Dimethyl fumerate Tecfidera®

C

Mitoxantrone Novantrone®

D

Most anecdotal reports of use during pregnancy and BF

Slightly increase risk of spontaneous abortions during early pregnancy

Per FDA discontinuation 2 months prior attempting conception Chelation therapy for both women and men prior to conception

Excellent review: Bruce Cree, MS Journal 2013

X

Post-Pregnancy Relapses 72% of women without relapse

Risk factors:

- Increased pre-pregnancy RR - Relapse during pregnancy - Higher EDSS univariant analysis only

Poor predictive value: - Only 13% by #1 + 2 - 72% by best predictive model

Confavreux NJEM 1998 , Vukusic Brain 2004

Pregnancy-related Relapse Risk MS should not dictate mode of delivery Most women are RRMS, severely disabled pt are rare No convincing data to argue against an epidural

PRIMS study and large prospective Italian study no impact on relapse rate or disability 1,2

NMSS expert panel: all forms anesthesia considered safe

Few anecdotal cases of complication in literature Remember steroid stress dose if indicated

1 Vukusic, Brain 2004. 2 Pasto BMC Neurology 2012

Breast-feeding

PRIMS study: no impact Exclusively

It Rocks!

MS management in post-partum setting

MS drugs No DMT approved

during lactation Most anecdotal reports

for glatiramer acetate (Copaxone®)

Greater concern for small molecules

Breast-feeding Conflicting data on

benefit of exclusive BF x 2 months

Monthly IV steroids with “pump & dump”

IVIG, no excretion into breast-milk

Resources Reproductive Issues Talking with Your MS Patient about Reproductive

Issues UW MEDCON (WWAMI): 1-800-326-5300 For your Patients: MS Navigator Program 1-800-

344-4867 (1-800 FIGHT MS)

Supplemental slides on treatments/reproductive safety information

Cree B , Mult Scler 2013 epub

*updated for DMF approval, adopted Cree B , Mult Scler 2013 epub C*

Post-partum MS management

IVIG - Not secreted in breast milk

Dose comparison1 150mg/kg d1 + 150mg/kg qm x 5 (n=75)

• Relapse-free 1st 3 months: 75.6% vs 81.5% (ns) • No increase in postpartum ARR 450, 300, 150mg/kg d1-3

+ 150mg/kg qm x 5 (n=76)

Single center2 Single dose 60g within 3 d relapse-free 1st 3 months: 75%

60g w/in 3d + 10g qm x5 94%

IVMP - “pump & dump” x 4-6h

Single center3

Naïve (n=22) relapse rate 1st 3months:

mean 2, SD 0.66

Monthly IVMP x 6 (n=20) mean 0.8, SD 0.41

Sex hormones

POPART’MUS trial4

progesterone po qd x 12 wk + estradiol transdermal qw x 12

pending

placebo 1 Haas, MS Journal 2007. 2 Haas, MS 2000. 3 de Seze, MS Journal 2004. 4 Vukusic J Neurol Sci

Dr. Dietrich’s case 43 year old female Remote history of a migraine with photophobia and transient right

facial droopiness in 2002, no migraines since Medical history of gluten intolerant and has hypothyroidism, seasonal

allergies, lumbar disc disease. She had a colloid goiter and a partial thyroidectomy, and has a history of dysmenorrhea, menorrhagia, and fibrocystic breast disease. Nonsmoker, no hypertension

Maternal aunt with MS, sister with migraine 4 year ago had vertigo for a few days after a vacation with

snorkeling 2 years ago vertigo for a few days without other symptoms 1/17/2015 she had abrupt onset of tinnitus of the right ear

followed by hearing loss in that ear and then some right facial numbness in the V2 distribution, lateral aspect

Dr. Dietrich’s case (cont.) Treated with prednisone for a few days by ENT and hearing

improved and was back to normal on an audiogram on 1/22/2015 Numbness persisted and increased a week later and then high

pitched tinnitus was also noted Brain MRI on 2/4/2015 with gad showed at least 8 punctuate foci

of periventricular and subcortical T2 and FLAIR hyperintensities though none were seen in the brain stem and there was no abnormality of the 7th or 8th cranial nerves

Tinnitus resolved after another 3 weeks and the numbness subsided but increased again on 3/5/2015

Initial neurology consultation on 3/11/2015 showed a normal neurological examination except for slight facial numbness in the lateral aspect of the V2 distribution on the right side

On 3/12/2015 she called about right facial rash and took a selfie and emailed it to us. It faded after 24 hours and has not recurred

Dr. Dietrich’s case (cont.) She had lab testing which showed a normal CBC, CMP

except K+ of 3.4, an ESR of 6, negative ANA, normal B12 of 461 and a low 25 OH vitamin D level of 14.1

She is now on vitamin D supplementation We performed an LP and the CSF showed no

oligoclonal bands, a TP of 46, and normal IgG concentration and synthesis rate. There was 1 WBC. A VEP study was normal

Repeat exam on 4/6/2015 was entirely normal. Her dentist indicated she has some TMJ dysfunction and

recommended a trial of occlusal splint therapy

Dr. Dietrich’s case (cont.) Currently we have no clear diagnosis and are

anticipating doing clinical follow up in 4-6 months and considering periodic repeat brain MRI scans

Any suggestions on: Relationship of hearing loss, tinnitus, facial numbness,

transient facial rash? Diagnosis? Other diagnostic tests? Recommended follow up?