Objective:

To evaluate ofatumumab (OMB) persistence, tolerability, safety, and effectiveness in people with MS (pwMS) over 36 months.

Background:

Ofatumumab (OMB) is a highly effective anti-CD20 monoclonal antibody approved for the treatment of relapsing multiple sclerosis (MS). Real-world data on OMB experience is limited.

Design/Methods:

Electronic medical records of pwMS treated with OMB (2020-2025) at three MS centers were reviewed. Baseline demographics, disease characteristics, and clinical and radiographic outcomes at 6-, 12-, 24-, and 36-month follow-up were analyzed using chi-square and t-tests and generalized linear and linear mixed-effects models with p<0.05 considered statistically significant.

Results:

A total of 329 PwMS (mean [SD] age 44.2 [10.2] years; 76% female; 78% White; mean disease duration 12.1 [9.0] years) initiated OMB; 276 (83.9%) had prior disease-modifying therapy (DMT) exposure, most commonly ocrelizumab/rituximab (32%). OMB persistence remained high (87.8%) with median [IQR] time to discontinuation 355 [93-724.5] days, mostly due to side effects/intolerability (22.5%) and disability progression (15.0%). Intolerability was primarily observed early, with 31.8% at 6 months decreasing to 11.4% by 36 months, mostly flu-like reactions. IgG levels remained stable at 36 months compared to baseline while the proportion of PwMS with low IgM increased (p=0.011). Infections occurred in 22%, 26%, 37%, and 44% at 6-, 12-, 24-, and 36-month follow-up, respectively (p<0.001), mostly due to upper respiratory and urinary tract infections. There were no unanticipated safety signals. The annualized relapse rate at 36 months was 0.02, an incident rate ratio of 0.21 compared to baseline (p<0.001). MRI activity decreased over time with new T2 lesions odds ratio (OR)=0.08 (p<0.001) and gadolinium-enhancing lesions OR=0.15 (p=0.010) at 36 months vs baseline.

Conclusions:

OMB was well-tolerated with robust persistence and effectiveness over 36 months. Safety was compatible with randomized clinical trial results. Infection rates rose with increasing treatment duration despite stable IgG, possibly due to IgM reduction.