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Following the publication of the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” in January 2019, new data has become available and an update is required. Whilst these updates do not change the overall recommendations in the guidelines, they add information, which we feel all neurologists should be aware of in order to provide the highest quality of information to all women with MS considering pregnancy.
(1) Interferon beta preparations in pregnancy
In September 2019, the EMA Committee for Medicinal Products for Human Use (CHMP) recommended a label change for interferon beta-1a, peginterferon beta-1a and interferon beta-1b, i.e. Avonex, Betaferon, Extavia, Plegridy and Rebif, stating that they may be considered during pregnancy if clinically indicated, and can be used during breastfeeding . This decision was based on data from interferon beta registries, national registries and post-marketing experience. However, data from exposure during second and third trimesters remains limited. The duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and it is likely that treatment was interrupted in many women when the pregnancy was detected and/or confirmed.
This supports the recommendation in the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” that these products are safe to be continued at least until...
This supports the recommendation in the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” that these products are safe to be continued at least until conception, in addition to extending this advice such that women should be offered the choice of continuation during pregnancy.
(2) Fingolimod (Gilenya)
In September 2019, the MHRA issued an alert on the safety of fingolimod (Gilenya) in pregnancy  after data from international pregnancy registers demonstrated that exposure in pregnancy leads to an estimated additional two to three major congenital malformations per 100 livebirths compared with the general population (a two-fold increase). Reported malformations include congenital heart disease, such as tetralogy of Fallot, atrial and ventricular septal defects, and renal and musculoskeletal abnormalities .
If a woman of childbearing potential is started on fingolimod, the advice in the summary of product characteristics is that she must be informed of the risk of teratogenicity and provided with a patient reminder card. She must have a negative pregnancy test before receiving the first dose and at suitable intervals during treatment as appropriate. She should be regularly advised to use effective contraception during treatment and for at least two months after stopping it. Women should be advised that recurrence of disease activity, which can be substantial, has been reported in around a quarter of women after stopping fingolimod to get pregnant [4-6].
In November 2018, the license for fingolimod was extended to include its use in for children and young adults (10-17 years) with MS . Due to limited treatment options in this group, fingolimod use in young women is anticipated to increase.
In our opinion, fingolimod is best avoided in women of childbearing age unless there is no other suitable treatment. Serious consideration should be given to proactively switching women of childbearing age who are taking fingolimod to an alternative DMD of at least similar efficacy well in advance of trying to conceive, and the possibility of unplanned pregnancy should be considered in all women of childbearing potential.
Work is ongoing to develop a UK MS Pregnancy Register; the above new information highlights the need for an independent register to inform practice.
Dr Ruth Dobson1,2* and Dr Peter Brex3; on behalf of all authors and the UK MS Pregnancy Register Steering Group
The following individuals and groups provided input into this update:
UK MS Pregnancy Register steering group (Dr David Rog, Dr Owen Pearson, Dr Katy Murray, Dr Stella Hughes, Dr Helen Ford, Dr Peter Brex and Dr Ruth Dobson)
UK consensus on pregnancy in multiple sclerosis: ABN guideline authors (Dr Catherine Nelson-Piercy, Dr Pooja Dassan, Megan Roberts, Prof Gavin GIovannoni)
Aoife Shields, Neuroscience Specialist Pharmacist
4. Hemat S, Houtschens M, Vidal-Jordana A, et al. Disease activity during pregnancy after Fingolimod withdrawal due to planning a pregnancy in women with multiple sclerosis. Poster presented at: 70th American Academy of Neurology Annual Meeting; April 21–27, 2018; Los Angeles, CA.
5. Meinl I, Havla J, Hohlfeld R, Kümpfel T. Recurrence of disease activity during pregnancy after cessation of fingolimod in multiple sclerosis. Mult Scler 2018;24(7):991–914. doi:10.1177/ 1352458517731913.
6. Novi G, Ghezzi A, Pizzorno M, et al. Dramatic rebounds of MS during pregnancy following fingolimod withdrawal. Neurol Neuroimmunol Neuroinflamm 2017;4(5):e377. doi:10.1212/ NXI.0000000000000377.