Tysabri (natalizumab) / Biogen, Royalty - LARVOL DELTA

Drug-Induced Pancreatitis Across UC Therapeutics: A Real-World Pharmacovigilance Study (ACG 2026) - " FAERS was queried for reports of pancreatitis associated with UC treatments including immunomodulators (azathioprine, mercaptopurine, methotrexate, tacrolimus), 5-aminosalicylates (mesalamine, balsalazide, olsalazine, sulfasalazine), anti-TNF agents (adalimumab, infliximab, golimumab, certolizumab pegol), integrin inhibitors (vedolizumab, natalizumab), IL-12/23 inhibitors (ustekinumab, risankizumab, guselkumab), JAK inhibitors (tofacitinib, upadacitinib), and S1P modulators (ozanimod, etrasimod). 83,046 reports with 612 pancreatitis cases were analyzed. Significantly elevated risk was observed with azathioprine (ROR 4.38, 95% CI 3.56-5.38), mesalamine (ROR 2.32, 95% CI 1.87-2.89), and infliximab (ROR 1.47, 95% CI 1.21-1.80; all p< 0.0001). Reduced risk was identified with adalimumab (ROR 0.60, 95% CI 0.49-0.74), vedolizumab (ROR 0.69, 95% CI 0.51-0.93), and ustekinumab (ROR 0.13, 95% CI 0.02-0.94)."

Adverse events • Clinical • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pancreatitis • Ulcerative Colitis • IL12A • ROR1

Perioperative Safety Profile of IBD Medications: A Comparative Study of Real World Pharmacovigilance Data (ACG 2026) - "Golimumab showed elevated UC sepsis (1.88), whereas Adalimumab and Certolizumab showed lower CD sepsis (0.54, 0.27) and Adalimumab lower DVT and PE in both indications. Vedolizumab showed elevated UC DVT and PE (~1.5); natalizumab elevated CD PE (2.30); ustekinumab an isolated UC ileus signal (14.15)... Thiopurines and Methotrexate showed the most consistent signals across both indications: elevated ROR for sepsis (Azathioprine UC: ROR 2.03, CD: 1.85; Mercaptopurine UC: 2.64, CD: 2.04; Methotrexate UC: 1.57), DVT (Methotrexate UC 4.15, CD 2.33; Azathioprine CD 2.23, Mercaptopurine UC 2.29), and PE (Methotrexate UC 1.96; Azathioprine CD 1.84). Azathioprine UC also showed elevated anastomotic leak (7.15). Among anti-TNFs, infliximab showed elevated CD sepsis (2.12), DVT (1.90), and PE (1.82), as well as UC DVT (1.32)."

Adverse events • Clinical • Real-world • Real-world evidence • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Septic Shock • Ulcerative Colitis

Prevalence and Outcomes of Hormone Therapy Use Among Menopausal Women With Inflammatory Bowel Disease (ACG 2026) - "However, patients with CD prescribed systemic HT had higher oral prednisone use, while osteoporosis/fracture outcomes were lower among patients receiving systemic HT. Figure: 1-Systemic non-transdermal HRT included oral estradiol, conjugated estrogens, esterified estrogens, synthetic conjugated estrogens A and B, oral progesterone, oral medroxyprogesterone, conjugated estrogens/bazedoxifene (Duavee), estradiol acetate vaginal ring (Femring), and norethindrone acetate/ethinyl estradiol (Femhrt). 2-Systemic transdermal HRT included estradiol/norethindrone acetate transdermal patch (CombiPatch), estradiol/levonorgestrel transdermal patch (Climara Pro), estradiol transdermal patches (Alora, Climara, Dotti, Estraderm, Lyllana, Minivelle, Vivelle-Dot), estradiol transdermal gel (EstroGel, Divigel), and estradiol transdermal spray (Evamist). 3-Local estrogen therapy included low-dose vaginal estradiol formulations (Estring, Imvexxy, Vagifem, and Yuvafem) and vaginal conjugated..."

Clinical • Cardiovascular • Coronary Artery Disease • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Pulmonary Embolism • Respiratory Diseases • Ulcerative Colitis

The Novel Use of Upadacitinib in Treatment of Refractory Ocrelizumab-Induced Colitis (OIC): A Case Report (ACG 2026) - "Suspected OIC was treated with IV methylprednisolone, leading to significant improvement; she was discharged on a prednisone taper and mesalamine 4.8 g daily...Symptoms remained well controlled on upadacitinib monotherapy until transition to natalizumab for dual MS and colitis management...Figure: Image 2. Histology from follow up colonoscopy with CD-20 immunostaining, demonstrating complete loss of CD20- positive B cells."

Case report • Clinical • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

A Tale of the Gut-Brain Axis: Concurrent Crohnâs Disease and Multiple Sclerosis (ACG 2026) - "She was treated with IV solumedrol with improvement in both GI and neurologic symptoms. Natalizumab, a monoclonal antibody targeting α4-integrin, has demonstrated efficacy in both relapsing MS and CD, providing a therapeutic option for patients with coexisting disease. This case highlights the importance of comprehensive evaluation and multidisciplinary management when caring for patients with concomitant IBD and MS Figure: CT Abdomen/Pelvis revealing pancolitis Figure: MRI demonstrating periventricular and subcortical white matter lesions concerning for MS"

CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

Disseminated CNS Blastomycosis in Crohn's Disease on Natalizumab: Transitioning From Systemic to Gut-Selective Anti-Integrin Therapy (ACG 2026) - "He was treated with IV amphotericin B with clinical and radiographic improvement and transitioned to a 12-month course of voriconazole. In such patients with severe systemic infection, transitioning from natalizumab to vedolizumab may be appropriate due to gut specificity and lack of impact on the blood brain barrier. This case highlights the nuances in considering biologics in the treatment of IBD and supports consideration of gut-selective vedolizumab when ongoing biologic therapy is needed after severe systemic infection."

CNS Disorders • Crohn's disease • Dermatitis • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Rare Diseases • ITGA4

Biologic drugs for induction and maintenance of remission in Crohn's disease: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "This review has supported evidence generation, but head-to-head comparative trials for key interventional subclasses or specific agents may be needed, as guided by key stakeholders; for example, on the use of biosimilar versions of medications out of patent. The role of concomitant purine analogues is a key confounding factor and future studies may not only want to investigate specifically the role of combinations, but also consider stratifying populations or purposefully excluding participants based on this key class of therapy to avoid such heterogeneity. Given the majority of evidence focusses on the outcomes of clinical remission and relapse, future studies may want to further consider other outcomes of clear interest to clinicians and patients, particularly endoscopic remission. Finally, long-term safety data are limited throughout the networks. Whilst future studies with longer follow-ups could provide increased data, it may be that study designs outside of..."

Clinical • Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL7R

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Digital signatures of fatigue and wearing-off symptoms in patients with multiple sclerosis under natalizumab. (PubMed, Neurotherapeutics) - P | "These exploratory findings indicate that, in this clinically stable cohort, WoS under NTZ do not reflect ongoing inflammatory or neurodegenerative disease activity, but rather align with fatigue-related motor changes detectable by high-adherence passive wearables. Dynamic wearable activity metrics warrant evaluation as digital endpoints for fatigue-focused interventions and clinical care."

Journal • CNS Disorders • Fatigue • Multiple Sclerosis • GFAP • NEFL • VCAM1

Late-Onset Neutropenia After Rituximab in Multiple Sclerosis: Incidence, Predictors, and Outcomes in a Retrospective Multicenter Cohort. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "In this large real-world cohort, high-grade LON (grades 3-4) events were rare and frequently complicated by infections. Mild (grade 2) LON events were often fluctuating and generally clinically uneventful. Rechallenge with rituximab was rarely complicated by serious adverse events. Prediction of LON remains challenging, highlighting the relevance of infection vigilance during anti-CD20 therapy."

Journal • Retrospective data • CNS Disorders • Hematological Disorders • Infectious Disease • Multiple Sclerosis • Neutropenia

Neonatal anemia after in-utero exposure to natalizumab: A real-world retrospective cohort study. (PubMed, Mult Scler Relat Disord) - "Natalizumab exposure during pregnancy, including third trimester, was not associated with an increased risk of clinically significant neonatal anemia in our unicentric retrospective cohort. These findings provide reassuring safety data, although larger prospective studies are required to help therapeutic management during pregnancy."

Journal • Real-world evidence • Retrospective data • Anemia • CNS Disorders • Hematological Disorders • Multiple Sclerosis

Predictors of high- versus low-intensity first-line multiple sclerosis treatments. (PubMed, Mult Scler J Exp Transl Clin) - "The first DMT filled was classified as either high- (natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine) or low-intensity (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, ozanimod)...The minority of MS patients initiated high-intensity treatment although this proportion increased over time, and later years were predictive of high-intensity treatment. Providers had a significant role in the approach selected."

Journal • CNS Disorders • Multiple Sclerosis

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review. (PubMed, Neurol Sci) - "Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research."

Journal • Review • CNS Disorders • Multiple Sclerosis • Small for Gestational Age

Use of subcutaneous natalizumab in routine care - Final results of a non-interventional, observational study (SISTER) in Germany and Austria. (PubMed, Ther Adv Neurol Disord) - "The final SISTER results suggest a patient preference for the SC vs. IV route and support the outcomes of the NOVA Part 2 trial, in which the preference of the SC route over IV was demonstrated in a cross-over design. The SC route allowed relevant time savings, and its good safety and tolerability argues for possible self-administration of SC natalizumab."

Journal • Observational data • CNS Disorders • Multiple Sclerosis

Early switching to ofatumumab avoids a rebound effect after natalizumab cessation in multiple sclerosis patients. (PubMed, Mult Scler J Exp Transl Clin) - "After a mean follow-up of 2.4 years (range: 6 months to 4 years), none of the patients had experienced any clinical relapse or magnetic resonance imaging reactivation. We confirm that ofatumumab is likely an effective option, using a short washout period following natalizumab discontinuation."

Journal • CNS Disorders • Multiple Sclerosis

Multimodal discovery of a pathogenic B cell-dependent T cell state in multiple sclerosis. (PubMed, Brain) - "We combine longitudinal, high-dimensional multimodal immune profiling in patients initiating ocrelizumab with a novel machine learning pipeline to resolve treatment-induced shifts in continuous immune cell states, revealing treatment-associated modulation of shared biological processes that act across the boundaries of discretely partitioned cell types...Finally, we demonstrate that blockade of lymphocyte trafficking across the blood-brain barrier with the anti-integrin α4 therapy natalizumab leads to enrichment of this cell state in the circulation, demonstrating a mechanistically concordant effect across distinct high-efficacy MS therapies. Together, our findings support a B cell-dependent, pathogenic T cell state which links peripheral immune activation to CNS-compartmentalised smouldering neuroinflammation across disease stages. Direct therapeutic manipulation of this T cell state may represent a key opportunity for targeting chronic neuroinflammation and facilitate..."

Journal • CNS Disorders • Epstein-Barr Virus Infections • Inflammation • Multiple Sclerosis • ITGA4

Ocrelizumab versus ofatumumab efficacy and safety after natalizumab discontinuation in multiple sclerosis: a retrospective real-world comparison. (PubMed, J Neurol) - No abstract available

Journal • Real-world evidence • Retrospective data • CNS Disorders • Multiple Sclerosis

Patient SAtisfaction with the TYSabri SC Formulation - A Swiss multi-centriC, prospective non-intervenTIONal study: the SATYSFACTION study. (PubMed, Ther Adv Neurol Disord) - "Findings were consistent across subgroups and time points. This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated, highly accepted, and patient-preferred alternative to IV_NTZ."

Clinical • Journal • Observational data • CNS Disorders • Multiple Sclerosis

Absolute and Relative Quantification of Glycation on Biotherapeutic IgGs Using Heavy Isotope-Labeled Proteins. (PubMed, J Biomol Tech) - "Glycation quantitation in IgGs such as Adalimumab (IgG1) and Natalizumab (IgG4) was performed. We expect this approach will apply to other PTMs."

Journal

Rasmussen Encephalitis, Case Report And Review Of The Literature (PubMed, Mali Med) - "Early injections of intravenous immunoglobulin and Natalizumab allowed a reduction in the frequency of seizures and cerebral inflammation. We report a case of Rasmussen encephalitis with a review of literature to shed light on this condition suffering from diagnostic delay or even diagnostic error."

Journal • Review • CNS Disorders • Epilepsy • Inflammation

Knowledge graph-guided multiple sclerosis identification and therapeutic trend analysis: Real-world evidence from two large healthcare systems. (PubMed, PLOS Digit Health) - "Among commonly used standard-effectiveness DMTs, MS-specific prescriptions declined after 2011 for interferon-beta (DMT-MS cosine similarity slope = -0.019 ± 0.011, p = 0.002) and glatiramer acetate (slope = -0.013 ± 0.012, p = 0.026), from 2013-2020 for fumarates (slope = -0.028 ± 0.015, p = 0.004), and after 2014 for S1P receptor modulators (slope = -0.026 ± 0.016, p = 0.005). Among commonly used higher-effectiveness DMTs, B-cell depletion therapies (slope = 0.051 ± 0.027, p = 0.001), particularly ocrelizumab (slope = 0.020 ± 0.016, p =0.032), showed a marked increase since 2018. Natalizumab usage peaked in 2011 (slopepre-2011 = 0.063 ± 0.013, ppre-2011 < 0.001; slopepost-2011= -0.027 ± 0.008, ppost-2011 < 0.001). Other DMT classes such as cell proliferation inhibitors and chemotherapy agents, showed low usage during follow-up. These findings provide real-world evidence from two large EHR-based MS cohorts, highlighting..."

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

EFFECTIVENESS AND SAFETY OF OZANIMOD AND NATALIZUMAB IN PATIENTS WITH COEXISTING INFLAMMATORY BOWEL DISEASE AND MULTIPLE SCLEROSIS: A EUROPEAN MULTICENTRE RETROSPECTIVE STUDY (UEGW 2026) - No abstract available

Retrospective data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

Real-world siponimod use in secondary progressive multiple sclerosis: the RESYZE study. (PubMed, Ther Adv Neurol Disord) - "Prior to siponimod, 44.3% received highly effective therapies: fingolimod (20.5%), rituximab (9.5%), ocrelizumab (5.2%), natalizumab (4.8%), and alemtuzumab (2.4%). In the study cohort, pwSPMS had high disability scores and comorbidities; more than half were unable to work, and over 40% had previously received high-efficacy therapies. After 1 year of siponimod treatment, most pwSPMS showed no signs of disease activity, with stabilized EDSS scores and relapses and new T2 or gadolinium-T1 lesions, as well as a favorable safety profile."

Clinical • Journal • Real-world evidence • CNS Disorders • Dyslipidemia • Mental Retardation • Metabolic Disorders • Multiple Sclerosis • Psychiatry

Effect of ocrelizumab on rates of retinal atrophy in relapsing multiple sclerosis. (PubMed, Mult Scler J Exp Transl Clin) - "EDSS and LA scores remained stable in ocrelizumab-treated PwRMS, and similar to natalizumab- or rituximab-treated PwRMS. GCIPL atrophy is attenuated and clinical function relatively stable in PwRMS treated with ocrelizumab."

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

Native structure of the therapeutic IgG4 α4β5 integrin antibody natalizumab. (PubMed, Biochim Biophys Acta Proteins Proteom) - "This conformational change may reflect what is happening by binding of antibodies to their cognate antigens, e.g., in the form of pathogen-associated molecular patterns on the surface of microorganisms, where the antibodies have an intrinsic ability to change conformation and expose their effector function sites. Thus, in the absence of their cognate antigen, antibodies circulate as closed, m-shaped, inactive molecules."

Journal • CNS Disorders • Multiple Sclerosis