Latest news with #DMTs
Medscape
13 hours ago
- Health
- Medscape
Perspective Shifts on the Use of MS Meds During Pregnancy
PHOENIX — Two new datasets support the use of potent disease-modifying therapies (DMTs) during pregnancy in women with active multiple sclerosis (MS), reinforcing a growing shift toward treatment when the potential benefit to the mother outweighs the risks. Both studies — one involving the anti-CD20 monoclonal antibody ofatumumab and the other the integrin receptor antagonist natalizumab — are observational, but they provide a foundation for taking a proactive rather than reactive approach to treating pregnant women with active MS, said Riley M. Bove, MD, associate professor of neurology, University of California San Francisco. Bove emphasized that a 'we-don't-know' approach is no longer acceptable when counseling pregnant women with active disease. As first author of the ofatumumab study — presented on May 29 at Consortium of Multiple Sclerosis Centers (CMSC) 2025 Annual Meeting— she followed up with a lecture the next day, explaining that evidence is now available to guide treatment decisions. Relevant Data While significant knowledge gaps remain about the relative risks of DMTs to fetal development and pregnancy outcomes, it is well established that women with active disease 'will be harmed if we do not help,' Bove said. She and others now believe that the available data, even if observational, are relevant and useful in guiding decisions that affect both maternal and fetal health. The new data on ofatumumab and natalizumab offer a clear example. In an ongoing registry, ofatumumab exposure has been documented in 669 pregnancies. Of these, 221 were reported prior to 2023, allowing for assessment of both short- and long-term outcomes. In most cases (87%), exposure occurred during the first trimester. Adverse outcomes were reported, including spontaneous abortions in 12.6% of cases, preterm births in 9.6%, and minor congenital malformations in two infants (< 1%). However, these rates are 'in line with the background rates observed in the general population,' Bove noted. She emphasized that such data are important when weighing treatment decisions against the known risks of active disease, which can lead to irreversible brain injury in the mother. The natalizumab data, presented as a late-breaking abstract at CMSC on May 30, reflected 16 years of experience at a single center. Tracking began in 2008, when two pregnancies were identified in women already receiving natalizumab. Through 2024, no increased risk for adverse pregnancy outcomes was observed, while natalizumab treatment was associated with meaningful improvements in MS disease control. A total of 58 pregnancies in 43 women have been tracked at the Rocky Mountain MS Clinic in Salt Lake City, according to Katrina Bawden, FNP-C, a nurse practitioner who has been involved since the registry began. Reevaluating Natalizumab She noted that outcomes were analyzed in women who discontinued natalizumab after learning they were pregnant as well as those who continued treatment into the third trimester. Among the 38 pregnancies in which natalizumab was stopped, 13 women experienced clinical relapses, and four others showed new lesions on MRI. In contrast, among the 20 pregnancies where treatment was continued, there were no relapses and no MRI evidence of disease activity. Pregnancy complications were observed, including one fetal malformation and 10 miscarriages, but Bawden noted that these figures — like those in the ofatumumab registry — are consistent with background rates. 'Of the three fetal deaths, all occurred in those who discontinued natalizumab,' she said. She noted that all 10 of the women who miscarried had healthy term full term deliveries in a subsequent pregnancy while remaining on natalizumab. Compared to the start of the tracking period, Bawden said the data have prompted clinicians at her clinic to reevaluate the benefit-risk balance of using natalizumab during pregnancy. 'Women at the Rocky Mountain MS Clinic who become pregnant while treated with natalizumab, using shared decision-making, are now given the option of continuing natalizumab every 8 weeks throughout pregnancy with the last dose scheduled at 34 weeks' gestation,' Bawden said. 'Illogical Guidance' Caring for pregnant women with MS is a complex challenge, given the incomplete information available. However, Bove — co-author of a 2024 paper on practical considerations for weighing the risks and benefits of DMT use during pregnancy — said that strictly following drug labeling is not helpful in guiding clinical decisions. She noted that current recommendations are inconsistent across drug classes, vary between the FDA and the European Medicines Agency, and often fail to reflect the latest science — resulting in guidance that is ultimately 'illogical.' Moreover, labeling continues to evolve, and pregnancy-related use of DMTs remains a dynamic area, with new data — such as the recent studies presented at CMSC — shaping clinical strategies. Bove emphasized that it is the clinician's responsibility to stay informed as the evidence develops, in order to support shared decision-making. This includes staying up to date on when to treat active disease during pregnancy, when to restart therapy if it was paused, and how to weigh the benefit-risk profile of DMTs for women who choose to breastfeed. When making MS treatment decisions during pregnancy, the adage 'first, do no harm' has traditionally focused on fetal risk. But Bove pointed out that withholding treatment may, in many cases, pose greater harm to the mother, underscoring the need for a balanced discussion that considers risks to both mother and fetus.
Medscape
13 hours ago
- Health
- Medscape
Evidence Shifts Perspective on MS Drug Use in Pregnancy
PHOENIX — Two new datasets support the use of potent disease-modifying therapies (DMTs) during pregnancy in women with active multiple sclerosis (MS), reinforcing a growing shift toward treatment when the potential benefit to the mother outweighs the risks. Both studies — one involving the anti-CD20 monoclonal antibody ofatumumab and the other the integrin receptor antagonist natalizumab — are observational, but they provide a foundation for taking a proactive rather than reactive approach to treating pregnant women with active MS, said Riley M. Bove, MD, associate professor of neurology, University of California San Francisco. Bove emphasized that a 'we-don't-know' approach is no longer acceptable when counseling pregnant women with active disease. As first author of the ofatumumab study — presented on May 29 at Consortium of Multiple Sclerosis Centers (CMSC) 2025 Annual Meeting— she followed up with a lecture the next day, explaining that evidence is now available to guide treatment decisions. Relevant Data While significant knowledge gaps remain about the relative risks of DMTs to fetal development and pregnancy outcomes, it is well established that women with active disease 'will be harmed if we do not help,' Bove said. She and others now believe that the available data, even if observational, are relevant and useful in guiding decisions that affect both maternal and fetal health. The new data on ofatumumab and natalizumab offer a clear example. In an ongoing registry, ofatumumab exposure has been documented in 669 pregnancies. Of these, 221 were reported prior to 2023, allowing for assessment of both short- and long-term outcomes. In most cases (87%), exposure occurred during the first trimester. Adverse outcomes were reported, including spontaneous abortions in 12.6% of cases, preterm births in 9.6%, and minor congenital malformations in two infants (< 1%). However, these rates are 'in line with the background rates observed in the general population,' Bove noted. She emphasized that such data are important when weighing treatment decisions against the known risks of active disease, which can lead to irreversible brain injury in the mother. The natalizumab data, presented as a late-breaking abstract at CMSC on May 30, reflected 16 years of experience at a single center. Tracking began in 2008, when two pregnancies were identified in women already receiving natalizumab. Through 2024, no increased risk for adverse pregnancy outcomes was observed, while natalizumab treatment was associated with meaningful improvements in MS disease control. A total of 58 pregnancies in 43 women have been tracked at the Rocky Mountain MS Clinic in Salt Lake City, according to Katrina Bawden, FNP-C, a nurse practitioner who has been involved since the registry began. Reevaluating Natalizumab She noted that outcomes were analyzed in women who discontinued natalizumab after learning they were pregnant as well as those who continued treatment into the third trimester. Among the 38 pregnancies in which natalizumab was stopped, 13 women experienced clinical relapses, and four others showed new lesions on MRI. In contrast, among the 20 pregnancies where treatment was continued, there were no relapses and no MRI evidence of disease activity. Pregnancy complications were observed, including one fetal malformation and 10 miscarriages, but Bawden noted that these figures — like those in the ofatumumab registry — are consistent with background rates. 'Of the three fetal deaths, all occurred in those who discontinued natalizumab,' she said. She noted that all 10 of the women who miscarried had healthy term full term deliveries in a subsequent pregnancy while remaining on natalizumab. Compared to the start of the tracking period, Bawden said the data have prompted clinicians at her clinic to reevaluate the benefit-risk balance of using natalizumab during pregnancy. 'Women at the Rocky Mountain MS Clinic who become pregnant while treated with natalizumab, using shared decision-making, are now given the option of continuing natalizumab every 8 weeks throughout pregnancy with the last dose scheduled at 34 weeks' gestation,' Bawden said. 'Illogical Guidance' Caring for pregnant women with MS is a complex challenge, given the incomplete information available. However, Bove — co-author of a 2024 paper on practical considerations for weighing the risks and benefits of DMT use during pregnancy — said that strictly following drug labeling is not helpful in guiding clinical decisions. She noted that current recommendations are inconsistent across drug classes, vary between the FDA and the European Medicines Agency, and often fail to reflect the latest science — resulting in guidance that is ultimately 'illogical.' Moreover, labeling continues to evolve, and pregnancy-related use of DMTs remains a dynamic area, with new data — such as the recent studies presented at CMSC — shaping clinical strategies. Bove emphasized that it is the clinician's responsibility to stay informed as the evidence develops, in order to support shared decision-making. This includes staying up to date on when to treat active disease during pregnancy, when to restart therapy if it was paused, and how to weigh the benefit-risk profile of DMTs for women who choose to breastfeed. When making MS treatment decisions during pregnancy, the adage 'first, do no harm' has traditionally focused on fetal risk. But Bove pointed out that withholding treatment may, in many cases, pose greater harm to the mother, underscoring the need for a balanced discussion that considers risks to both mother and fetus.
Health Line
10-05-2025
- Health
- Health Line
Secondary Progressive Multiple Sclerosis (SPMS) and Switching Treatments
Improvements in safety, efficacy, and specificity have raised questions around the benefits and risks of switching treatments for this type of MS, especially from fingolimod to siponimod. There are four main types of multiple sclerosis (MS), with relapsing remitting MS (RRMS) being the most common. However, some people who have RRMS may eventually develop secondary progressive multiple sclerosis (SPMS). SPMS features a steady decline in neurological function that can occur with or without relapses. With SPMS, a relapsing-remitting disease pattern is still possible, though relapses may become less frequent. Neurological symptoms may also continue to decline as underlying nerve damage and neuron loss naturally worsen through age, stress, and other degenerative processes. Like other presentations of MS, doctors treat SPMS using disease-modifying therapies (DMTs). In 2010, the drug fingolimod (Gilenya) became the first oral DMT approved by the Food and Drug Administration (FDA) for certain types of MS, including RRMS and SPMS. Since then, advancements in MS treatment have continued to evolve. In particular, a new drug therapy called siponimod (Mayzent) was approved in 2019 specifically for use in SPMS. As a result, researchers have started to weigh the pros and cons of switching people who have SPMS from fingolimod to siponimod. Reasons why you might want to switch treatments According to a review from 2023, there are several reasons you may want to consider switching from fingolimod to siponimod for SPMS. Specific approval from the FDA Siponimod is specifically approved for treating SPMS, which is supported by clinical trial data. Fingolimod is approved for relapsing forms of MS, which can include SPMS. However, the medication does not have significant clinical trial data focused specifically on SPMS. Fewer side effects Both siponimod and fingolimod are S1P receptor modulators. These drugs activate S1P receptors and prevent immune cells from attacking the myelin sheath around nerves. However, siponimod is more selective than fingolimod when it comes to which S1P receptors it targets. This helps reduce the risk of side effects. Less intensive monitoring The broad S1P action of fingolimod means the drug is associated with certain risks, particularly: slowed heart rate (bradycardia) liver damage eye swelling increased infection risk When you're prescribed fingolimod, the first dose is given under medical supervision, and heart monitoring is required for 6 hours afterward. If no problems are detected, you can continue to take the medication on your own at home. But you'll need to work with your doctor to set a schedule for ongoing routine monitoring. Siponimod appears to have a lower risk of heart-related side effects due to its more targeted mechanism of action. As a result, it requires less strict monitoring. However, you still need to work with your doctor to discuss how often to schedule checkups to monitor how well the medication is working. Shorter washout time Siponimod has a shorter half-life (30 hours) than fingolimod (6 to 9 days). A shorter half-life suggests it may clear from your system faster. Better remyelination Siponimod targets specific S1P receptor subtypes, particularly S1P5, which is involved in myelin-producing cell survival and function. Myelin is the protective layer around the nerves that can become inflamed and damaged in MS. As a result, research suggests that this targeted approach that siponimod provides may offer enhanced repair of myelin (remyelination) effects compared with the broad S1P action of fingolimod. Factors to consider when switching Not everyone may benefit from switching from fingolimod to siponimod. If your SPMS is well managed on fingolimod and you're not experiencing significant side effects, there's no guarantee your MS will do better on siponimod. Switching off an effective treatment isn't always recommended just because a new medication might offer some benefits. Switching off fingolimod has also been associated with certain risks, like disease reactivation, in some people. When you switch from fingolimod to a more targeted drug like siponimod, experts believe your inflammatory response may become upregulated, which can promote active disease. Another consideration before switching from fingolimod to siponimod is genetic testing. Siponimod is not recommended for use in people who have certain variants of the CYP2C9 gene, which slow siponimod metabolism and can increase the risk of side effects. Switching from fingolimod to siponimod Clinical trial data on siponimod suggests most people can immediately switch to it from fingolimod with no major side effects or reactions. Before you make the switch, your doctor will order genetic screening to check for known CYP2C9 variants. If your results indicate you're a candidate for siponimod, the next step is to discontinue your current DMT. Some DMTs, like teriflunomide (Aubagio), may require a washout period where you have to wait for the medication to fully clear from your system before starting siponimod. Even though siponimod has more favorable safety parameters than fingolimod, it can still cause the same types of side effects. Before starting siponimod, a cardiac evaluation, blood screening, eye exam, and skin exam are all recommended to ensure no underlying conditions might increase your risk. Other disease-modifying therapies for SPMS In addition to fingolimod and siponimod, FDA-approved DMTs used in the treatment of SPMS include: ocrelizumab (Ocrevus) mitoxantrone (Novantrone) Additional DMTs for SPMS are in development and in clinical trials. In December 2024, the FDA granted the designation of 'breakthrough therapy' to the drug tolebrutinib for use in non-remitting SPMS. Tolebrutinib belongs to a class of medications called Bruton's tyrosine kinase (BTK) inhibitors. Other BTK inhibitors being investigated for use in MS include: orelabrutinib fenebrutinib BIIB091 Talking with your healthcare team SPMS is a complex condition that affects each person differently. Finding the right combination of medication and supportive therapies often requires trial and error. Switching from fingolimod to siponimod starts with a conversation with your healthcare team. Discuss with your doctor why you want to switch medications, and come prepared with a list of your questions and concerns. Questions you may want to ask your doctor include: Do you recommend switching from fingolimod to siponimod? How will siponimod change my treatment plan? What tests do I need to have done? Am I at an increased risk of certain side effects? Is there a washout period? Do any of my other medications prevent me from taking siponimod? How will I know if the treatment is effective? How soon? What happens if I miss a dose? What should I expect from the first few weeks of treatment?
