Balancing Innovation with Practical Realities in an Evolving Treatment Landscape
Executive Summary
The AAN 2025 conference showcased advancements in neurological care, including new therapies and clinical strategies. While these developments offer potential, their adoption requires careful consideration of preliminary data, clinical risks, logistical challenges, and financial barriers. This report highlights key updates in Alzheimer’s disease, myasthenia gravis, multiple sclerosis, movement disorders, and broader topics like AI and physician wellness, providing a practical and evidence-based perspective for neurologists, enriched by direct physician insights from the event.
Key Highlights:
- Alzheimer’s Disease: Early interest in GLP-1 receptor agonists and updates on LEQEMBI and KISUNLA, tempered by preliminary data and safety concerns.
- Myasthenia Gravis: A growing array of biologics with a mechanism-based treatment framework, though cost and access remain barriers.
- Multiple Sclerosis: Mixed results for TOLIBRUTINIB and critical guidance for managing MS during pregnancy, with relapse risks emphasized.
- Movement Disorders: Subcutaneous therapies for Parkinson’s and new options for cervical dystonia, despite logistical hurdles.
- Other Notable Topics: AI tools for documentation, novel treatments for GBS and narcolepsy, and a focus on resident education and wellness, with practical challenges noted.
This report integrates unaided perspectives from physicians who attended the conference, offering a comprehensive view of the event’s insights and their real-world implications.
Alzheimer’s Disease
Alzheimer’s discussions at AAN 2025 focused on emerging and established treatments, but their benefits must be weighed against uncertainties and challenges.
- GLP-1 Receptor Agonists: Dr. Sheehan remarked, “one of the key takeaways for me was the growing interest in GLP-1 receptor agonists for patients with Alzheimer’s disease,” spotlighting Dr. Paul Edison’s presentation which “suggested potential benefits for non-diabetic Alzheimer’s patients,” including “possible clinical improvements and even a reduction in tau formation.” These findings, while promising, are preliminary, based on small cohorts, and lack long-term safety data. Neurologists should approach this as a research frontier rather than a practice-ready option, awaiting larger trials.
- Disease-Modifying Therapies: Dr. Sheehan shared that new data on LEQEMBI (lecanemab) from the CLARITY AD trial showed “slower cognitive decline and general stability in clinical indices,” though he cautioned about “a few small hemorrhages in patients with the ApoE4 variant.” Dr. Racela added, “there’s potential for a subcutaneous version of Leqembi,” enhancing convenience, while noting KISUNLA’s “once-a-month infusion” contrasts with LEQEMBI’s twice-monthly schedule but comes with a “slightly higher ARIA rate.” These ARIA risks (amyloid-related imaging abnormalities), including cerebral edema or bleeding, necessitate regular MRI monitoring and careful patient selection (e.g., avoiding ApoE4 homozygotes). At over $20,000 annually, accessibility remains a hurdle, particularly for uninsured patients.
- Anti-Tau Therapies: Dr. Racela highlighted that “anti-tau therapies are showing promise,” noting “since tau pathology doesn’t directly affect neurons, there’s no associated ARIA risk.” He mused, “I could see myself considering both [anti-tau and anti-amyloid] approaches in certain cases,” suggesting a synergistic potential, though efficacy remains unproven in large-scale studies.
Clinical Considerations: Screen patients for ApoE4 status and discuss cost-coverage options upfront. Monitor treated patients with quarterly MRIs to manage ARIA risks effectively.
Myasthenia Gravis
New biologics are expanding treatment options for myasthenia gravis, but their integration involves navigating efficacy, logistics, and equity.
- Expanding Treatment Landscape: Dr. Racela observed “an explosion of treatment options in recent years,” listing VYVGART (efgartigimod), RYSTIGGO (rozanolixizumab), ZILBRYSQ (zilucoplan), ULTOMIRIS (ravulizumab), and SOLIRIS (eculizumab). He praised VYVGART HYTRULO, stating it “offers similar efficacy and tolerability as IV but with more convenience,” though it requires professional administration. These biologics, targeting pathways like FcRn or complement, offer precision over steroids or IVIG, but limited comparative trials and costs—often exceeding $100,000 yearly—restrict access.
- Treatment Framework: Dr. Racela outlined a mechanism-based approach: “Milder patients may start with steroids or steroid-sparing therapies,” while “more severe or refractory cases may begin directly with biologics” like “anti-FcRn agents like VYVGART or RYSTIGGO.” He added, “if needed, therapy may escalate to B-cell depleting agents like rituximab or the newer inebilizumab.” Vaccine timing complicates anti-complement therapies, as he noted, “patients must be vaccinated (e.g., for meningococcus)” before starting ULTOMIRIS, often requiring delays or prophylaxis.
Clinical Considerations: Assess insurance and infusion center availability before prescribing biologics. Tailor plans, starting with steroids and escalating based on symptom control and tolerability.
Multiple Sclerosis
MS sessions at AAN 2025 offered updates on therapeutics and pregnancy management, critical for clinical practice.
- New Therapeutics: Dr. Wilner reported on TOLIBRUTINIB, stating, “in the HERCULES trial, the drug showed a 31% decrease in disease progression for patients with secondary progressive MS.” However, he cautioned, “in the GEMINI trial, TOLIBRUTINIB had more gadolinium-enhancing and T2 MRI lesions” compared to TERIFLUNOMIDE, suggesting persistent inflammation. This mixed profile, combined with high costs, requires neurologists to weigh clinical gains against imaging concerns. Dr. Sheehan noted interest in “antibody-based therapies” for optic neuritis in MS, aiming for “quicker and more complete recovery” beyond steroids.
- MS and Pregnancy: Dr. Rose provided actionable insights: “Therapies like ocrelizumab and rituximab appear safe when used prior to pregnancy,” and “treatment can be continued during lactation without clear risk,” supported by the SOPRANINO trial finding “infant serum levels were undetectable.” She warned, “stopping natalizumab or S1P receptor modulators around pregnancy carries a high risk of relapse—up to 70% of women relapse during pregnancy or within one year postpartum,” recommending natalizumab continuation until “30–34 weeks’ gestation” with newborn monitoring for anemia.
Clinical Considerations: For TOLIBRUTINIB, monitor MRI trends and clinical response. In pregnancy, counsel on relapse risks and coordinate with obstetricians for natalizumab timing and infant monitoring.
Movement Disorders
Parkinson’s disease and cervical dystonia updates underscored practical advancements.
- Parkinson’s Disease: Dr. Racela highlighted “new subcutaneous therapies” like “subcutaneous carbidopa/levodopa infusions” and “apomorphine-based therapies,” noting ANAPKO’s potential for severe off-periods. Dr. Sheehan added, “new data on extended-release carbidopa/levodopa formulations showed improved sleep scores and reduced night-time motor fluctuations.” These options reduce oral regimen reliance, but administration requires training and equipment costing thousands upfront, plus ongoing expenses.
- Cervical Dystonia: Dr. Racela confirmed, “while Botox remains the mainstay, new formulations of botulinum toxins have gained indications,” offering flexibility, though success hinges on injection precision.
Clinical Considerations: Screen Parkinson’s patients for infusion suitability (e.g., support systems) and explore subsidies. For dystonia, invest in ultrasound-guided injection training.
Other Notable Topics
Broader trends shaping neurology were also explored.
- AI in Neurology: Dr. Wilner enthused, “I was impressed by the demonstrations of ‘ambient scribe’ technologies,” which “convert the dialogue into structured clinical notes,” noting “many physicians in the audience were already using these tools.” High setup costs and integration challenges limit scalability, but AI could ease documentation burdens in well-funded practices.
- GBS and Narcolepsy Treatments: Dr. Wilner reported TEGOPRUBART (ANX005) for GBS showed “dramatic improvement—patients walked sooner, spent less time on ventilators,” while REBOXETINE for narcolepsy led to “a 33% reduction in cataplexy episodes,” though cost and distribution details are pending.
- Resident Education and Wellness: Dr. Racela emphasized “case-based learning” and “financial literacy” for residents, addressing “student loan burden” to “set them up for long-term financial success,” alongside wellness activities like jiu-jitsu.
- Neurology and Pregnancy: Beyond MS, Dr. Rose noted, “Botox is now considered safe to use during pregnancy,” while “the World Health Organization strongly discourages the use of valproic acid” due to fetal risks.
Clinical Considerations: Trial AI in well-funded settings, evaluating time savings versus cost. Prioritize mentorship for residents over unproven wellness trends.
Conclusion
The AAN 2025 meeting revealed a neurological treatment landscape defined by personalization and convenience, yet tempered by high costs, logistical hurdles, and mixed data. For neurologists, bridging innovation and practice requires balancing clinical evidence with real-world feasibility.
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