DMDs & conceiving... sorry, long post!

[Emi87]

Hi everyone, hope you’re all as well as can be.
I was hoping some of you could share with me your thoughts and experiences...

I’m currently on tysabri, my infusions have been moved to 6 weekly and after the pandemic, my neurologist will change my medication completely. He has suggested gilenya and ocrevus. So, of course, I’ve been looking into them.

My partner and I were hoping to try for a baby soon, it would be our first and last together ( we both have children from previous relationships). My son is 6 and I came off tysabri while I was pregnant with him but I believe women are now often continuing on tysabri throughout pregnancy. I’ve read that it is not safe to conceive on gilenya or ocrevus and you need to be off these drugs for a time before you can even conceive. I don’t much like the idea of this I feel like the best option would be to conceive while on tysabri, come off it while pregnant (don’t mind not bring on anything while pregnant as pregnancy is great for my ms, as it is for many ladies ) then start new treatment after baby is born. Although I do have some concerns about starting a new treatment With a newborn, not knowing how effective the new treatment would be.

Have any of you experienced having babies while on ocrevus or gilenya? How was it managed?
For those of you on gilenya and ocrevus, do they work well for you?

I’m sorry for the long post, my head is all over the place... I blame the broody hormones

Thankyou
Emi xx

[NHE]

Hi Emi,
The prescribing information for Gilenya states...

Fetal Risk: May cause fetal harm. Advise females of reproductive
potential of the potential risk to a fetus and to use an effective method of
contraception during treatment and for 2 months after stopping
GILENYA. (5.8, 8.1, 8.3)

5.8 Fetal Risk
Based on findings from animal studies, GILENYA may cause fetal harm when administered to a pregnant woman. In animal reproduction studies conducted in rats and rabbits, developmental toxicity was observed with administration of fingolimod at doses less than the recommended human dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Because it takes approximately 2 months to eliminate GILENYA from the body, advise females of reproductive potential to use effective contraception to avoid pregnancy during and for 2 months after stopping GILENYA treatment [see Use in Specific Populations (8.1, 8.3)].

8.1 Pregnancy
Pregnancy Exposure Registry:
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to GILENYA during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the GILENYA Pregnancy Registry by calling 1-877-598-7237, sending an email to gpr@quintiles.com, or visiting www.gilenyapregnancyregistry.com.

Risk Summary:
Based on findings from animal studies, GILENYA may cause fetal harm when administered to a pregnant woman. Data from prospective reports to the GILENYA Pregnancy Registry (GPR) are currently not sufficient to allow for an adequate assessment of the drug-associated risk for birth defects and miscarriage in humans. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m² ) basis. The most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis (see Data). Advise pregnant women of the potential risk to a fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations:
In females planning to become pregnant, GILENYA should be stopped 2 months before planned conception. The possibility of severe increase in disability should be considered in women who discontinue or are considering discontinuation of GILENYA because of pregnancy or planned pregnancy. In many of the cases in which increase in disability was reported after stopping GILENYA, patients had stopped GILENYA because of pregnancy or planned pregnancy [see Warnings and Precautions (5.9)].

Data Animal:
Data: When fingolimod was orally administered to pregnant rats during the period of organogenesis (0, 0.03, 0.1, and 0.3 mg/kg/day or 0, 1, 3, and 10 mg/kg/day), increased incidences of fetal malformations and embryofetal deaths were observed at all but the lowest dose tested (0.03 mg/kg/day), which is less than the recommended human dose (RHD) on a mg/m² basis. Oral administration to pregnant rabbits during organogenesis (0, 0.5, 1.5, and 5 mg/kg/day) resulted in increased incidences of embryofetal mortality and fetal growth retardation at the mid and high doses. The no-effect dose for these effects in rabbits (0.5 mg/kg/day) is approximately 20 times the RHD on a mg/m² basis. When fingolimod was orally administered to female rats during pregnancy and lactation (0, 0.05, 0.15, and 0.5 mg/kg/day), pup survival was decreased at all doses and a neurobehavioral (learning) deficit was seen in offspring at the high dose. The low-effect dose of 0.05 mg/kg/day is similar to the RHD on a mg/m² basis.

8.3 Females and Males of Reproductive Potential:
Pregnancy Testing:
The pregnancy status of females of reproductive potential should be verified prior to starting treatment with GILENYA [see Use in Specific Populations (8.1)]. Contraception Before initiation of GILENYA treatment, females of reproductive potential should be counseled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with GILENYA [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1)]. Since it takes approximately 2 months to eliminate the compound from the body after stopping treatment, the potential risk to the fetus may persist and women should use effective contraception during this period [see Warnings and Precautions (5.8, 5.13)].

The Ocrevus prescribing information has a warning regarding PML.

Progressive Multifocal Leukoencephalopathy (PML):
PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

The Ocrevus prescribing information has the following warning regarding pregnancy.

8.1 Pregnancy:

Risk Summary:
OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to OCREVUS have not been studied in clinical trials. The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown [see Warnings and Precautions (5.2)]. Following administration of ocrelizumab to pregnant monkeys at doses similar to or greater than those used clinically, increased perinatal mortality, depletion of B-cell populations, renal, bone marrow, and testicular toxicity were observed in the offspring in the absence of maternal toxicity [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data:
Animal Data Following intravenous administration of OCREVUS to monkeys during organogenesis (loading doses of 15 or 75 mg/kg on gestation days 20, 21, and 22, followed by weekly doses of 20 or 100 mg/kg), depletion of B lymphocytes in lymphoid tissue (spleen and lymph nodes) was observed in fetuses at both doses. Intravenous administration of OCREVUS (three daily loading doses of 15 or 75 mg/kg, followed by weekly doses of 20 or 100 mg/kg) to pregnant monkeys throughout the period of organogenesis and continuing through the neonatal period resulted in perinatal deaths (some associated with bacterial infections), renal toxicity (glomerulopathy and inflammation), lymphoid follicle formation in the bone marrow, and severe decreases in circulating B-lymphocytes in neonates. The cause of the neonatal deaths is uncertain; however, both affected neonates were found to have bacterial infections. Reduced testicular weight was observed in neonates at the high dose. A no-effect dose for adverse developmental effects was not identified; the doses tested in monkey are 2 and 10 times the recommended human dose of 600 mg, on a mg/kg basis.

In summary, neither drug looks good for use during pregnancy. The warning about PML with Ocrevus is also of concern especially since you're known to be JCV positive.

[Emi87]

Thank you for your reply... hmm I did read a couple of things about pml and ocrevus also, confuses me slightly, not sure why he would offer me ocrevus think an email to my neuro is in order lol. Thanks again xx