Tysabri (natalizumab) / Biogen, Royalty - LARVOL DELTA

Serum drug levels and JCV assay discrepancies after switching from originator to biosimilar natalizumab. (PubMed, BMJ Neurol Open) - "Drug levels, ADAb, leukocytes and NfL remained similar before and after switching, and GFAP decreased, of uncertain relevance. The marked rise in JCV-positivity on the Immunowell assay underscores the need for harmonisation of anti-JCV antibody testing."

Journal • CNS Disorders • Fatigue • Multiple Sclerosis • Musculoskeletal Pain • Pain • GFAP • NEFL

Advancements in Pharmacotherapy and Mobile Health Applications for Self-Management in Multiple Sclerosis: A Comprehensive Review. (PubMed, Recent Pat Biotechnol) - "Monoclonal antibodies define the upper limit of efficacy in current MS therapy, but sustainability depends on safety oversight and patient engagement. Oral formulations remain clinically pragmatic first-line options. The synergy between pharmacotherapy and mobile health technology offers a pathway to transform adherence, monitoring, and outcome optimization in future MS management."

Journal • CNS Disorders • Immunology • Infectious Disease • Multiple Sclerosis

No association between the wearing-off effect and α4-integrin receptor saturation in natalizumab treated patients with relapsing-remitting multiple sclerosis. (PubMed, Neurotherapeutics) - "Our findings suggest that WOE is not related to reduced α4-integrin receptor saturation and thus does not reflect diminished pharmacodynamic efficacy of NTZ. These results provide reassurance regarding the continued therapeutic effect of NTZ in patients experiencing WOE."

Journal • CNS Disorders • Fatigue • Multiple Sclerosis

Cytomegalovirus Drives the Development of Cytotoxic CD4+ T Cells in Patients With Multiple Sclerosis. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "CMV was implicated as a dominant driver of development of highly cytotoxic CD4+ T cells, as these cells were markedly enriched in CMV-seropositive individuals. This comprehensive phenotypic atlas of CD4 CTL advances our understanding of their development and highlights potential targets for diagnosing, treating, and preventing MS progression."

Journal • CNS Disorders • Cytomegalovirus Infection • Immunology • Infectious Disease • Multiple Sclerosis • CD4

International Expert Opinion on Optimal Switching to Cladribine Tablets from Other High-Efficacy Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: Opportunities and Challenges. (PubMed, Neurol Ther) - "An international group of experts in the care of RMS reviewed the current evidence and their clinical practice in order to provide recommendations on the optimal therapeutic use of cladribine tablets (CladT, an immune reconstitution therapy for RMS) in patients previously managed on anti-trafficking agents (S1P modulators, natalizumab) or an anti-CD20 agent. It is important to keep the interval between withdrawal of a previous anti-trafficking DMT (especially S1P modulators) and initiation of CladT as short as possible if the switch is intended to address breakthrough RMS disease activity, especially with regard to the prevention of rebound RMS disease activity. Immune reconstitution therapy with CladT may also provide an opportunity to plan for pregnancy in the absence of continuous DMT."

Journal • Review • CNS Disorders • Inflammation • Multiple Sclerosis

SUPERNEXT: Personalized Extended Interval Dosing of Natalizumab in Relapsing Remitting Multiple Sclerosis (clinicaltrials.gov) - P4 | N=300 | Recruiting | Sponsor: Amsterdam UMC, location VUmc | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Demyelination Reported with Biologic Therapies for Rheumatologic and Inflammatory Bowel Diseases: Insights from FAERS (AAN 2026) - "Mechanistic classes included: anti–tumor necrosis factor (TNF)-α agents, anti-integrin antibodies (excluding natalizumab), anti-interleukin agents (including IL-12/23, IL-23, IL-17, IL-6, and IL-1 inhibitors), B-cell targeted therapies (excluding rituximab), and T-cell co-stimulation modulators... Safety signals for demyelination were identified with TNF-α inhibitors (infliximab, adalimumab, certolizumab pegol, golimumab, and etanercept) with a PRR of 7.34 (95% CI: 6.75–7.98), and abatacept, a selective T-cell co-stimulation modulator (PRR: 2.12; 95% CI: 1.41–3.20). No safety signals were observed for IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab), IL-23 inhibitors (mirikizumab, guselkumab, tildrakizumab, risankizumab), and anti-α4β7 integrin (vedolizumab). Reporting counts were insufficient for IL-6 inhibitors (tocilizumab and sarilumab), IL-1 inhibitors (anakinra, canakinumab, and rilonacept), and B-lymphocyte stimulator..."

Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • IL12A • IL17A • IL23A

Comparative Efficacy of 35 Disease-modifying Therapies in Relapsing-remitting MS: A Network Meta-analysis Identifying Top Performers for Relapse, MRI Activity, and Disability Progression (AAN 2026) - "At 6 months, SC IFNbeta-1b (RR 0.14) and SC Ofatumumab (RR 0.33) were associated with the lowest disability progression... Alemtuzumab and the Ocrelizumab formulations were highly effective for relapse prevention, while Ponesimod + DMF and Natalizumab formulations reduced MRI lesions. Mitoxantrone was associated with long-term prevention of disability progression."

Retrospective data • CNS Disorders • Multiple Sclerosis

From Brain to Bone Marrow: Concurrent Use of Bruton's Tyrosine Kinase Inhibition and Anti-CD20 Therapy in Relapsing Multiple Sclerosis With Chronic Lymphocytic Leukemia (AAN 2026) - "Natalizumab was maintained until CLL progression with associated dermatologic symptoms prompted transition to acalabrutinib plus subcutaneous ofatumumab. This case underscores the therapeutic complexity of managing concurrent RMS and CLL. It suggests that B-cell–directed therapies, BTKi and anti-CD20, can be used in combination. A crucial consideration is the need to overlap immunotherapies when transitioning from an immune-trafficking agent in the setting of high lymphocyte counts, to reduce the risk of rebound disease."

Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Immunology • Leukemia • Multiple Sclerosis

The Exit Strategy: Clinical Outcomes and Safety of De-escalating High-efficacy Therapies in Multiple Sclerosis (AAN 2026) - ""Stable" PwMS transitioned from natalizumab (50%), ocrelizumab (49%) or alemtuzumab (1%). Most PwMS were de-escalated to cladribine (49%) or a fumarate (41%)... These findings suggest that age may be an influential factor in determining stability after de-escalation and de-escalation from ocrelizumab appears to be safer than from natalizumab. Therefore, the decision to de-escalate should be based on individual patients' characteristics."

Clinical • Clinical data • CNS Disorders • Multiple Sclerosis

Urinary Tract Infections and Urosepsis in Multiple Sclerosis: Insights from FDA Pharmacovigilance Data (AAN 2026) - "Ocrelizumab had the greatest association with UTI, and natalizumab, alemtuzumab, and interferon-beta-1a exhibited safety signals for both outcomes across all sex and age subgroups. This real-world pharmacovigilance analysis identifies disproportionate reporting of UTI and urosepsis across several MS DMTs, underscoring their contribution to morbidity and mortality. These associations likely reflect both therapy-related immunologic effects and disease-intrinsic factors, particularly neurogenic bladder dysfunction. These findings highlight the need for vigilant infection surveillance, proactive bladder management, and individualized risk assessment in MS care."

Adverse events • CNS Disorders • Immunology • Infectious Disease • Multiple Sclerosis • Nephrology • Urology

Appendicitis and multiple sclerosis disease-modifying therapies: a disproportionality analysis of the FDA adverse event reporting system. (PubMed, Mult Scler Relat Disord) - "Patient counseling on early appendicitis warning signs and indications for urgent evaluation may be warranted for people with MS on DMTs."

Adverse events • Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Multiple Sclerosis

Real-world Utilization of a Novel Multi-analyte Blood-based Biomarker Panel, the Octave® Multiple Sclerosis Disease Activity (MSDA) Test in Clinical Practice Across the United States (AAN 2026) - "Baseline demographics include mean age of 52.0 years, 77.0% female, 76.8% White, 14.7% Black, and 4.4% Hispanic.Among patients with DMT data, 44.4% were on high-efficacy DMTs (anti-CD20s, natalizumab, cladribine, alemtuzumab) at their latest test; 34.2% were not on a DMT. This report highlights the growing use of the MSDA Test in US clinical practice and its clinical utility for tracking meaningful change. Ongoing research is essential to fully realize the Octave® MSDA test's impact and ensure smooth integration into clinical workflows."

Biomarker • Clinical • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Disparities in Geographic Access to Infusion Centers Does not Impact the Use of High Efficacy Infusion Disease Modifying Therapies in Multiple Sclerosis (AAN 2026) - "A multivariable logistic regression model was used to evaluate the association between geographic access to infusion centers and the use of infusion DMTs (CD20 monoclonal antibodies, natalizumab, alemtuzumab, cyclophosphamide) adjusting for age, sex, race, ethnicity, education, MS disease duration, MS course, patient determined disease steps (PDDS), area deprivation index (ADI), and rural-urban commuting code (RUCA). Disparities to geographic access to infusion centers exist but distance did not impact the use of high efficacy infusion DMTs for patients. These results suggest that geographic barriers to resources can be mitigated to deliver highly effective treatments."

Clinical • CNS Disorders • Multiple Sclerosis

Serum Neurofilament Light Chain Utility in Multiple Sclerosis Clinic: Real-world Retrospective Data (AAN 2026) - "DMTs were classified as low efficacy (LeDMT: teriflunomide, fumarates, interferons, glatiramer acetate), moderate (MeDMT: S1P modulators, cladribine), high (HeDMT: B-cell therapy, natalizumab), and no DMT...Among patients on B-cell therapies, rituximab showed lowest average sNfL level of 1.81 pg/ml and ublituximab highest at 2.06 pg/ml... sNfL levels correlate with efficacy of DMTs and potentially the duration of therapy. Patients with high sNfL levels despite HeDMT, have high MRI disease burden, potentially requiring closer monitoring. Comorbidities and variable test techniques limit the generalisability of sNfL in current clinical practice."

Real-world • Real-world evidence • Retrospective data • CNS Disorders • Diabetes • Metabolic Disorders • Multiple Sclerosis • NEFL

FROM INCORPORATION TO IMPACT: REAL-WORLD BUDGET ADVANTAGE OF CLADRIBINE IN MULTIPLE SCLEROSIS WITHIN A BRAZILIAN PRIVATE HEALTH PLAN (ISPOR 2026) - "Cladribine substantially reduced healthcare resource utilization and MS-related costs in real-world practice. It also demonstrated the lowest 4-year budget impact compared with natalizumab and ocrelizumab, reinforcing its economic advantage for private payers. Continuous monitoring of treatment adherence and persistence is recommended to maximize clinical and economic outcomes."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Cladribine for the Treatment of Relapsing Multiple Sclerosis: The Northern Ireland Experience (AAN 2026) - "Subsequently, patients commenced ofatumumab (n=6), ocrelizumab (n=4), and natalizumab (n=1)... This study evaluated the Northern Ireland experience of cladribine use in patients with active RMS. Of those treated with cladribine, one quarter had a relapse with MRI activity, and following this received another highly effective DMT. The limitations of this observational study include a small sample size and relatively short median duration of follow up of 6 years, but highlight the importance of real-world data."

CNS Disorders • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis

Is Cladribine a Suitable Strategy after Natalizumab in MS? Real-world Outcomes (AAN 2026) - "With median 75-day washout between natalizumab and cladribine, 40% experienced relapse within one year. Prolonged washout periods may have contributed to this reactivation rate, warranting further investigation to establish transition protocols."

Clinical • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Maternal and neonatal outcomes following natalizumab use during pregnancy in women with multiple sclerosis: A multicenter observational study. (PubMed, J Clin Neurosci) - "Continuing natalizumab treatment until late pregnancy was associated with better postpartum clinical and radiological outcomes. Neonatal anthropometric measures were comparable to reference child growth standards. These findings support that late pregnancy natalizumab continuation may be a viable high efficacy strategy for women with highly active MS."

Journal • Observational data • CNS Disorders • Multiple Sclerosis

Effects of disease modifying therapy on cognitive proficiency in pediatric-onset multiple sclerosis (POMS). (PubMed, Mult Scler Relat Disord) - "In this cross-sectional cohort, all patients treated with B-cell depletion therapies performed within the average to high average range. While those treated with dimethyl fumarate displayed more variability, their mean/median scores fell within the average range. In contrast, patients treated with natalizumab demonstrated low average to below average scores, suggesting immune-modulating therapeutics such as dimethyl fumarate and B-cell depletion may potentially be more beneficial than therapies that only prevent immune cell ingress into the central nervous system."

Journal • CNS Disorders • Multiple Sclerosis • Pediatrics

COST-EFFECTIVENESS ANALYSIS OF UBLITUXIMAB FOR THE TREATMENT OF RELAPSING REMITTING MULTIPLE SCLEROSIS (ISPOR 2026) - "In Model 2, ublituximab was compared with ofatumumab using weighted ARR for teriflunomide, as both treatments were evaluated against the same active comparator in phase III clinical trials... Results from Models 1 and 2 highlight the sensitivity of cost-effectiveness outcomes to comparator selection and indirect comparison methodology, underscoring the importance of robust comparative effectiveness evidence when evaluating high-efficacy DMTs for RRMS."

Cost effectiveness • HEOR • CNS Disorders • Multiple Sclerosis

ECONOMIC VALUE OF RELAPSE RATE REDUCTION WITH OFATUMUMAB VERSUS COMPARATOR DISEASE-MODIFYING THERAPIES IN RELAPSING MULTIPLE SCLEROSIS: A FIVE-YEAR BUDGET IMPACT ANALYSIS WITH CLINICAL OUTCOME OFFSETS (ISPOR 2026) - "Comparator ARRs from phase III trials and literature: ofatumumab 0.11 (ASCLEPIOS I/II, Hauser NEJM 2020); interferon β-1a IM 0.61; interferon β-1a SC 0.86; teriflunomide 0.37; fingolimod 0.18; natalizumab 0.25; rituximab 0.20... Ofatumumab's superior ARR profile (0.11, lowest in class) generates substantial clinical value through relapse avoidance, translating into quantifiable cost offsets that reduce net budget impact by approximately one-quarter. These findings support value-based pricing negotiations incorporating ARR-driven outcomes"

Clinical • Clinical data • HEOR • CNS Disorders • Multiple Sclerosis • IFNB1

Progressive Multifocal Leukoencephalopathy with Immune Reconstitution Inflammatory Syndrome and Good Outcome in an Immunocompetent Patient: Case Report and Literature Review (AAN 2026) - "It typically occurs in patients with cellular immunosuppression or those receiving immunomodulatory therapies such as natalizumab... This case highlights that PML can occur in apparently immunocompetent patients, although an occult immunodeficiency potentially predisposing to both PML and invasive BCC is suspected. It also suggests that PML-IRIS in such patients may not invariably predict poor outcomes."

Case report • Clinical • Review • Basal Cell Carcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • CNS Disorders • Gynecology • Immunology • Non-melanoma Skin Cancer • Rare Diseases • Squamous Cell Carcinoma

Access to High-efficacy Therapies for Multiple Sclerosis Under Medicaid: Variation in Coverage and Utilization Across States (AAN 2026) - "HETs such as anti-CD20 agents and natalizumab are central to modern MS care and improve outcomes when initiated early... Significant variability in Medicaid drug formularies corresponds to disparities in real-world use of high-efficacy MS therapies. Policy efforts harmonizing coverage criteria across states and plans may reduce inequities and promote timely, effective treatment for Medicaid enrollees."

Clinical • Medicaid • Reimbursement • US reimbursement • CNS Disorders • Multiple Sclerosis

Quantitative Assessment of Remyelination by Q-space Myelin Map and its Association With Functionality and Quality of Life in Multiple Sclerosis (AAN 2026) - "The q-Space Myelin Map (qMM) is a diffusion-based MRI technique sensitive to myelin content, allowing noninvasive quantification of remyelination.Design/ We conducted a 6-month observational study using qMM in 21 RRMS patients who initiated or switched to natalizumab or other disease-modifying therapies (DMTs)... In summary, qMM appears to be a promising noninvasive biomarker of remyelination. Imaging evidence of myelin restoration was associated with improved disability and quality-of-life measures, supporting the potential of qMM to inform clinical decision-making and advance myelin repair research."

HEOR • CNS Disorders • Multiple Sclerosis