Impact of smoking on clinical outcomes in ocrelizumab-treated multiple sclerosis

Smoking has been consistently linked to accelerated disease progression in multiple sclerosis (MS), but its impact in the context of modern disease-modifying therapies such as ocrelizumab remains unclear. This study evaluated the association between smoking and MS-related clinical outcomes based on claims-based data in patients actively treated with ocrelizumab.

We conducted a retrospective, claims-based cohort study using the TriNetX research network, which aggregates electronic health records from 106 healthcare organizations. Adults with MS treated with ocrelizumab between March 1, 2017, and December 31, 2024, were included. Patients were stratified by current smoking status (ICD-10 code F17.21), and 1:1 propensity score matching was performed to control for confounding. The primary outcomes included incidence of optic neuritis, extremity weakness, seizures, urinary incontinence, depression, all-cause hospitalizations, and mortality. Cox proportional hazards models were used to compare outcomes between smokers and non-smokers.

Among 5998 patients (mean age 45.0 years; 60 % female), smokers had similar rates of optic neuritis (HR 1.33; 95 % CI, 0.93-1.90), but higher risk of extremity weakness (HR 1.43; 95 % CI, 1.17-1.76), seizures (HR 3.24; 95 % CI, 2.11-4.98), urinary incontinence (HR 1.69; 95 % CI, 1.32-2.16), depression (HR 1.69; 95 % CI, 1.41-2.04), hospitalizations (HR 1.51; 95 % CI, 1.21-1.87), and mortality (HR 2.11; 95 % CI, 1.42-3.15) compared to non-smokers.

In patients with MS treated with ocrelizumab, smoking was associated with significantly worse neurologic and overall outcomes. These findings highlight the importance of addressing smoking as a modifiable risk factor in MS care, even among those receiving advanced immunotherapy.