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The following summarizes some of the highlights from Day 3 of the American Academy of Neurology annual meeting (AAN), Chicago, Illinois, April 18-22, 2026.

Trial results for fenebrutinib in RMS
Use of sNfL in practice
De-escalation: three strategies
Ofatumumab: long-term data
Pregnancy outcomes in MS, NMOSD and MOGAD
Seasonality of AQP4-IgG+ NMOSD and MOGAD
West Nile neuroinvasive disease reported with immunosuppression

CONGRESS HIGHLIGHTS – WEDNESDAY EDITION

Trial results for fenebrutinib in RMS
Fenebrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, was superior to teriflunomide in reducing relapses, according to the results of the FENhance 1 and 2 trials in RMS (Oh et al. AAN 2026;LB2.5). The parallel studies compared fenebrutinib 200 mg BID to teriflunomide 14 mg/day for 96 weeks. Mean age was about 36 years, median time from symptom onset was about 3-4 years and median EDSS was 2.0-2.5. About 15-20% were previously treated. The annualized relapse rate (ARR) was 0.061 and 0.054 with fenebrutinib in the two studies compared to 0.125 and 0.13 with teriflunomide. The number of Gd+ lesions was 0.08 in both studies with fenebrutinib compared to 0.27 and 0.37 with teriflunomide in FENhance 1 and 2, respectively. The number of new/enlarging T2 lesions was 1.23 and 1.08 with fenebrutinib vs. 5.14 and 6.15 with teriflunomide. There was no benefit with fenebrutinib with respect to composite confirmed disability progression (EDSS, T25FW, 9HPT). The hazard ratio vs. teriflunomide for cCDP was a nonsignificant 0.80 and 0.87 in the two trials. The rate of serious adverse events was comparable in FENhance 1 (8.6% vs. 8.9%), but higher with fenebrutinib vs. teriflunomide in FENhance 2 (11.2% vs. 6.1%). The rate of serious infections was similar (2.1% vs. 2.2%, and 2.7% vs. 1.3%). Two patients in the fenebrutinib group met Hy’s Law criteria (ALT >3 x ULN + bilirubin >2 x ULN); the adjudication committee determined that the likelihood of another cause was >50%. One Hy’s Law case was confirmed with fenebrutinib; the event occurred on day 29 before biweekly liver function testing was instituted. There was one confirmed Hy’s Law case in the teriflunomide arm in a patient with a history of alcoholic hepatitis following heavy alcohol consumption. There were seven deaths in the fenebrutinib groups (0.93%) compared to one (0.13%) in the teriflunomide groups.

Use of sNfL in practice
Two studies have reported on the use of serum neurofilament-light (sNfL) levels in clinical practice. A retrospective study at the Mayo clinic compared 338 MS patients with and without elevated sNfL at baseline; median age was 39 years (Chouhdry et al. AAN 2026;P3.004). The median sNfL level was 23.1 pg/mL in the elevated group and 6.6 pg/mL in the non-elevated group. Patients with elevated sNfL levels were significantly more likely to have Gd+ lesions on brain MRI (51% vs. 17%) or spinal cord MRI (30% vs. 12%) at three months. Comorbidities, including obesity, renal disease and diabetes, did not influence sNfL levels.

A European study found that only 40% of newly-diagnosed MS patients had heard of NfL testing, but most agreed to testing once they were more fully informed (Gonzalez-Suarez et al. AAN 2026;P5.003). In addition, 62.5% of patients said they would be more at ease with their MRI or follow-up visit if they were told that their sNfL level was below their z-score. Patients willing to undergo sNfL testing were more informed about MS and had better performance on quality of life and cognitive measures, but also reported greater treatment regret.

De-escalation: three strategies
Numerous strategies have been proposed for de-escalating DMTs in older MS patients. Three different approaches were addressed at AAN 2026. The first study (N=52) looked at stopping anti-CD20 therapy in older patients (mean age 61 years) with stable disease (Omari et al. AAN 2026;S40.008). The mean duration on anti-CD20 therapy was 48 months; most stopped due to infections or patient preference. Over the follow-up period, one patient (1.9%) had a relapse and three patients (5.7%) had new MRI lesions four years after their last treatment. Disability was stable in 79%, worsened in 15% and improved in 6%.

The second strategy was de-escalation from a high-efficacy to a lower-efficacy DMT (Osen et al. AAN 2026;P2.010). The patients who achieved stable disease two years after discontinuation were older (mean age at de-escalation 50 years) and were relapse-free for two years prior to de-escalation. Patients successfully transitioned from natalizumab, ocrelizumab or alemtuzumab to cladribine or a fumarate.

The third approach was to de-escalate to long-term use of cladribine (Stastna et al. AAN 2026;P2.006). The registry study looked at patients who completed the two-year course of treatment (N=352). At 5 years, 41% were relapse-free and 71% were free of 3-month CDP. The relapse-free rate increased to 85% in the year following re-treatment. In the group aged ≥50 years, all were relapse-free after another cladribine course and two-thirds required no further treatment. The authors concluded that cladribine is a suitable exit strategy for older patients considering de-escalation/discontinuation.

Ofatumumab: long-term data
The risk of serious infections or malignancies is stable with ongoing exposure to ofatumumab, according to 8-year safety data from the ALITHIOS extension study (n=2531) (Pardo et al. AAN 2026;P9.006). For patients in the continuous ofatumumab group, mean age was 37.5 years and total drug exposure time was 8487.6 patient-years (PY). The exposure-adjusted incidence rate (EAIR) for serious adverse events in the overall population was 3.94 per 100 PY at 8 years, a slight decrease from the 4.06/100 PY reported in the 7-year analysis. The EAIR for serious infections was 1.21/100 PY (0.80/100 PY excluding COVID-19), a reduction from the incidence of 1.37/100 PY reported at year 7. The EAIR for malignancies was 0.33/100 PY. Immunoglobulin levels were generally stable: 96.5% of patients had IgG levels above the lower limit of normal (LLN) at all assessments and 64.7% had all assessments >LLN for IgM. IgM levels initially decreased before stabilizing after week 144, with mean values remaining above the LLN at all time points. Results were comparable in the subgroup of recently-diagnosed and newly-diagnosed subgroup (n=546). The EAIR in this group was 3.67/100 PY for serious adverse events, 1.21/100 PY for serious infections (0.66/100 PY excluding COVID-19), and 0.38/100 PY for malignancies.

Pregnancy outcomes in MS, NMOSD and MOGAD
The Pregnancy outcomes Intensive Monitoring (PRIM) program is an ongoing study of pregnancy outcomes in women treated with ofatumumab. To date, outcomes for 232 pregnancies are known (Bove et al. AAN 2026;P11.002). Overall, there have been 180 live births (78%), 33 spontaneous abortions (14%), 2 ectopic pregnancies (1.7%) and 1 stillbirth (0.4%). The rate of congenital abnormalities was 1.7% for major and 1.0% for minor anomalies (vs. 4% in general population). Major malformations included urinary, heart defect and nervous system (where the pregnancy was terminated).

The German pregnancy registry of patients with MS and neuromyelitis optica spectrum disorders (NMOSD) reported pregnancy outcomes for 64 patients with NMOSD or myelin oligodendrocyte antibody disease (MOGAD) (Blum et al. AAN 2026;P8.006). Two-thirds had AQP4-IgG-positive NMOSD, two had AQP4-IgG-negative NMOSD and 20 had MOGAD. Mean age was 31 years. Prior to conception, 73% were exposed to treatment such as anti-CD20 therapy (48%); azathioprine (16%); or glatiramer acetate, satralizumab, inebilizumab or tocilizumab (1.6% each). There were 56 live births (89%); mean birth weight was 3311 grams (vs. mean 3255 g in U.S., 3367 g in Canada for healthy women). A total of 11% were pre-term and 18.5% were small for gestational age. There were five spontaneous abortions and two elective abortions. The rate of congenital malformations was 5.4% (vs. 3-4% in healthy women). Malformations included peripheral pulmonary stenosis, persistent ductus arteriosus, and osteogenesis imperfecta. Four women (6.3%) with AQP4-IgG+ NMOSD had a relapse during pregnancy. The proportion relapsing in the first year postpartum was 25.0%: 14% pretreated with azathioprine, 43% treated with rituximab, and 43% who were untreated. The proportion of MOGAD patients who relapsed was 14% pretreated with azathioprine, 43% with rituximab and 43% untreated.

Seasonality of AQP4-IgG+ NMOSD and MOGAD
Initial attacks show a seasonal pattern in MOGAD and, to a lesser extent MS, but seasonality was not detectable for NMOSD, according to a new U.S. multicentre study (Roy et al. AAN 2026;P3.005). The analysis included 420 patients with MOGAD, 1128 patients with RMS and 318 with AQP4+ NMOSD. In the MOGAD group, onset attacks were most common in November, January and March. In MS, onset attacks were more likely in January, March and April. For NMOSD, onset attacks were more common in February and March, but the pattern was more inconsistent. A previous study reported that the highest positivity rates on laboratory testing occurred in winter both for AQP4-IgG and MOG-IgG, and the lowest seropositivity rates were in summer (Vorasoot et al. ECTRIMS 2025;P022). That study also found that NMOSD or MOGAD onset was highest in January.

West Nile neuroinvasive disease reported with immunosuppression
The University of North Dakota reported seven cases of West Nile neuroinvasive disease in patients on anti-CD20 therapy (Montgomery et al. AAN 2026;P11.012). Six cases were MS patients receiving ocrelizumab, and one case was a patient with myasthenia gravis on rituximab. All of the patients were female, aged 23-64 years, and on anti-CD20 therapy for variable lengths of time. The initial presentation was fever with CSF pleocytosis. The incidence of West Nile infection in Canada was 304 cases in 2025, of which 296 were acquired domestically. The most common neurological presentation is encephalitis (Burton et al. Can J Neurol Sci 2004;31:185-193).

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