Risk of Noninfectious Uveitis Associated With Disease-Modifying Therapies for Multiple Sclerosis

Anthony J Cordisco; Fangming Jin; Ali G Hamedani; Brian L VanderBeek

doi:10.1016/j.ajo.2026.04.032

Risk of Noninfectious Uveitis Associated With Disease-Modifying Therapies for Multiple Sclerosis

Am J Ophthalmol. 2026 May 5:288:199-206. doi: 10.1016/j.ajo.2026.04.032. Online ahead of print.

Authors

Anthony J Cordisco¹, Fangming Jin², Ali G Hamedani³, Brian L VanderBeek⁴

Affiliations

¹ From the Department of Neurology (A.J.C. and A.G.H.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² Department of Ophthalmology (F.J., A.G.H., B.L.V.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Preventive Ophthalmology and Biostatistics (F.J.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ From the Department of Neurology (A.J.C. and A.G.H.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Ophthalmology (F.J., A.G.H., B.L.V.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology, and Informatics (A.G.H. and B.L.V.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Leonard Davis Institute of Health Economics (A.G.H. and B.L.V.), University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Ophthalmology (F.J., A.G.H., B.L.V.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology, and Informatics (A.G.H. and B.L.V.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Leonard Davis Institute of Health Economics (A.G.H. and B.L.V.), University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: brian.vanderbeek@pennmedicine.upenn.edu.

PMID: 42097475
DOI: 10.1016/j.ajo.2026.04.032

Abstract

Purpose: Multiple sclerosis (MS) is associated with an increased risk of noninfectious uveitis (NIU). Whether disease-modifying therapies (DMTs) for MS alter this risk is unknown. Our objective was to determine the comparative risk of NIU after DMT initiation for MS.

Design: Retrospective clinical cohort study using Optum's deidentified Clinformatics Data Mart database, which is comprised of medical claims for patients enrolled in commercial and Medicare Advantage insurance plans from January 1, 2000, to June 30, 2022.

Participants: Adults with MS, defined by ≥3 diagnosis codes on separate dates, who received ≥1 DMT prescription and had ≥2 years of prior enrollment. Participants could contribute multiple treatment episodes if they switched therapies.

Methods: Users of interferons, fumarates, nucleic acid synthesis inhibitors/sphingosine-1-phosphate (S1P) modulators, natalizumab, and anti-CD20 monoclonal antibodies were compared to glatiramer acetate as the reference.

Main outcome measures: Marginal Cox models with robust sandwich covariance matrix estimation were used to calculate adjusted hazard ratios (aHR) for incident NIU, defined as a new International Classification of Diseases code for NIU with a 2nd confirmatory diagnosis within 120 days. A sensitivity analysis varied this definition to require a new concurrent corticosteroid prescription or ocular injection within 120 days of diagnosis. DMT-specific propensity score models were constructed using multivariable logistic regression with generalized estimating equations to calculate overlap weights for adjustment. Participants were censored if they switched treatments, underwent intraocular surgery, or disenrolled.

Results: Across 48,221 treatment episodes for 43,501 patients, median follow-up ranged from 562 to 703 days. Compared to glatiramer acetate, the NIU incidence was lower for nucleic acid synthesis inhibitors/S1P modulators (aHR 0.14, 95% CI: 0.07-0.29), fumarates (aHR 0.51, 95% CI: 0.36-0.74), anti-CD20 (aHR 0.66, 95% CI, 0.51-0.85), and interferons (aHR 0.67, 95% CI: 0.50-0.91), but not natalizumab (aHR 0.87, 95% CI: 0.61-1.24). Sensitivity analysis confirmed findings for fumarates (aHR 0.56, 95% CI: 0.38-0.82) and nucleic acid synthesis inhibitors/S1P modulators (aHR 0.16, 95% CI: 0.08-0.33).

Conclusions: Certain DMT classes are associated with a protective effect for NIU in MS. If confirmed, these medications could be targeted for personalized MS treatment and potentially repurposed to treat NIU in other patient populations.