Comparable effectiveness and persistence of ocrelizumab and natalizumab

A retrospective analysis compared 2 widely used and highly effective MS treatments: ocrelizumab and natalizumab. Over 5 years, effectiveness was comparable. On the other hand, ocrelizumab was associated with a higher incidence of mild to moderate adverse events (AEs), but had comparable to higher treatment persistence than NTZ.

Ocrelizumab and natalizumab are both highly efficacious monoclonal antibodies widely used in clinical practice. Dr Elena Barbuti (Sapienza University of Rome, Italy) set up a study which analysed data from patients with MS who started either therapy between 2010 and 2019, followed up in the University Hospitals of Rome or Napoli, and had either relapsing or progressive MS.

The study population consisted of 308 participants, including 140 who used ocrelizumab and 168 who used natalizumab. In this original cohort, participants in the ocrelizumab group were older (mean age 49.9 vs 42 years; P<0.001), less often active (42.1% vs 87.5%; P<0.001), and less frequently treatment-naïve (22.9% vs 33.9%; P=0.03). Propensity score matching resulted in a cohort of 140 participants, comprising 70 pairs of participants, with one participant in each pair treated with ocrelizumab and the other with natalizumab. The mean follow-up in this cohort was 55.9 months. The probability of being free from relapses, MRI activity, Expanded Disability Status Scale (EDSS) progression, and reaching No Evidence of Disease Activity-3 (NEDA-3) after 12, 30 and 60 months is shown below (see Figure) [1].

Figure: Probability of being free from relapses, MRI activity, EDSS progression and to reach NEDA-3 after 12, 30 and 60 months [1]



MRI, magnetic resonance imaging; EDSS, Expanded Disability Status Scale; NEDA-3, No Evidence of Disease Activity; NTZ, natalizumab; OCR, ocrelizumab

Dr Barbuti said that no significant differences were found between natalizumab and ocrelizumab in the following outcomes:

1. Number of relapses: HR 0.41 (95% CI 0.11–1.57; P=0.19).
2. MRI activity: HR 0.37 (95% CI 0.10–1.44; P=0.15).
3. EDSS progression: HR 1.43 (95% CI 0.60–3.40; P=0.42). NB: All patients with confirmed disability progression experienced Progression Independent of Relapse Activity (PIRA).
4. NEDA-3: HR 0.64 (95% CI 0.34–1.24; P=0.19).

Of note, ocrelizumab was associated with a higher risk of adverse events (AEs): OR 4.50 (95% CI 1.53–16.50; P=0.01). Of the 140 participants, 19 developed one or more AEs; 15 were treated with ocrelizumab. However, most AEs were blood test abnormalities, and none were life-threatening. Treatment discontinuation rates were comparable for both drugs, but a sensitivity analysis performed excluding patients transferred to other MS centres revealed that NTZ-treated patients had a higher probability of treatment discontinuation [OR=0.26 (0.09–0.67, p=0.008)]

1. Barbuti E, et al. Ocrelizumab versus natalizumab in multiple sclerosis: a propensity-score study. OPR-037, EAN Congress 2025, 21-24 June, Helsinki, Finland.

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Posted on 3 September 20253 September 2025