MKSAP: 29-year-old woman is evaluated during a routine follow-up examination of multiple sclerosis

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 29-year-old woman is evaluated during a routine follow-up examination of multiple sclerosis, which was diagnosed 3 years ago. The patient says she wishes to discontinue her oral contraceptive and attempt to become pregnant. She has no other personal or family medical history of note. Medications are fingolimod, vitamin D, and an oral contraceptive.

On physical examination, temperature is 36.9 °C (98.5 °F), blood pressure is 100/50 mm Hg, pulse rate is 66/min, and respiration rate is 14/min; BMI is 27. A right afferent pupillary defect is noted. All other physical examination findings are normal.

Besides discontinuing the oral contraceptive, which of the following is the most appropriate next step in management?

A. Advise against pregnancy
B. Discontinue fingolimod
C. Substitute mitoxantrone for fingolimod
D. Substitute teriflunomide for fingolimod

MKSAP Answer and Critique

The correct answer is B. Discontinue fingolimod.

In addition to discontinuing the oral contraceptive in preparation for attempting conception, fingolimod should be stopped. An oral disease-modifying therapy for multiple sclerosis (MS), fingolimod is a sphingosine-1-phosphate receptor modulator that restricts activated lymphocytes to lymph nodes and may also have direct neuroprotective effects. Fingolimod significantly reduces the relapse rate, risk of disability progression, and accumulation of new lesions on MRI. This drug has been associated with rare but potentially harmful side effects, including increased rates of serious herpesvirus infection, hypertension, bradycardia, lymphopenia, liver function abnormalities, and macular edema. Fingolimod is classified as a pregnancy category C drug, and thus its safety in human pregnancy is not clearly established. Although category C medications are indicated in some patients if the benefits outweigh the risks, the hormonal state of pregnancy itself is protective against MS activity, and thus discontinuing a disease-modifying drug during pregnancy is considered relatively safe.

Advising this patient against pregnancy is clearly inappropriate. The adverse effect of pregnancy on MS progression is a commonly held misconception. In fact, observational studies have found reduced risks for conversion to clinically definite MS from clinically isolated syndromes and reduced risks for conversion from relapsing MS to secondary progressive MS in women with multiple pregnancies.

Mitoxantrone is an anthracenedione chemotherapeutic agent that reduces lymphocyte proliferation and decreases the relapse rate and disability progression in MS. Despite mitoxantrone’s efficacy, cardiac toxicity and the risk of secondary leukemia have significantly limited its use. Mitoxantrone is classified as a pregnancy category X drug and is contraindicated during pregnancy.

The MS drug teriflunomide is the active metabolite of leflunomide, which inhibits pyrimidine biosynthesis and interferes with the interaction between T lymphocytes and antigen-presenting cells. Substituting teriflunomide for fingolimod is inappropriate because teriflunomide is classified as pregnancy category X drug and is contraindicated during pregnancy.

Key Point

  • Fingolimod is classified as a pregnancy category C drug (safety in human pregnancy not clearly established) and thus should not be used by women who are pregnant or planning to become pregnant.

This content is excerpted from MKSAP 17 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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