SPECIAL REPORT

Real-world efficacy and safety
Switching anti-CD20 therapies
Patient-reported outcomes (PROs)
Effect on cortical lesions

The efficacy and safety of the anti-CD20 agent, ofatumumab, in the treatment of multiple sclerosis were among the key topics addressed at the Americas Committee on Treatment and Research in MS (ACTRIMS) Forum, held February 27-March 1, 2025 in West Palm Beach, Florida. Ofatumumab is a novel anti-CD20 formulation for self-injection, and recent studies have focussed on its tolerability, convenience and patient-reported outcomes in clinical practice.

Real-world efficacy and safety
The CRONOS-MS study examined the real-world effectiveness of ofatumumab at 33 centres in Spain (Aguera Morales et al. ACTRIMS Forum 2025;P397). The interim analysis included 93 RMS patients; median age was 42 years, mean time from diagnosis was 7.6 years; and mean baseline EDSS score was 2.0. Two-thirds of patients were previously treated: 32 (34%) with a moderate-efficacy DMT and 28 (30%) with a high-efficacy agent. The annualized relapse rate (ARR) decreased from 0.75 in the 12 months prior to ofatumumab to 0.05 at month 12 of treatment. The ARR reduction was 96% in treatment-naïve patients and in those previously treated with a moderate-efficacy DMT, and 83% in patients previously treated with a high-efficacy DMT. EDSS was unchanged at 12 months. Five patients (5.4%) had new/enlarging T2 lesions; there were no Gd+ lesions after starting ofatumumab. No serious adverse effects were reported. The one-year discontinuation rate was 2.1%.

A separate analysis of the Madrid EMCAM database identified 211 patients (median age 40.1 years) treated with ofatumumab for >1 year (Gomez Estevez et al. ACTRIMS Forum 2025;P419). Median disease duration was 8.7 years; baseline EDSS was 2.2.  One-half of the cohort had been previously treated with a high-efficacy DMT. ARR decreased 96% (0.5 to 0.02) at one year after ofatumumab initiation. The number of Gd+ lesions decreased from 0.6 to 0.04 at one year. EDSS score was unchanged. IgG levels were generally stable, decreasing from 10.36 g/L at baseline to 9.9 g/L at 12 months. Treatment was well tolerated. One-third reported adverse effects after the first dose, most commonly flu-like symptoms. Injection site pain was uncommon (4.3%).

Switching anti-CD20 therapies
OLIKOS is an ongoing phase IIIb study of switching from intravenous anti-CD20 therapy (ocrelizumab or rituximab) to ofatumumab. In the interim analysis of 102 patients, all subjects met the primary efficacy endpoint of no change/reduction in Gd+ lesions at six months after the switch (Alvarez et al. AAN 2024;P10-6.006). IgG levels were stable (9.9 g/L at baseline, 9.8 g/L at 6 months) after initiating ofatumumab. Similar results were seen in a post-hoc analysis of treatment efficacy in Black (n=20) and Hispanic (n=30) subgroups over 12 months (Alvarez et al. ACTRIMS Forum 2025;P093). Median EDSS scores were higher in Black (3.0) and Hispanic (3.25) patients compared to White patients (2.5). No Gd+ lesions were identified in any subgroup at month 12, suggesting a broad-based efficacy across patient groups. The most common adverse effects in all subgroups were COVID-19 infection (30.4%), headache (13.7%), and fatigue (11.8%).

Patient-reported outcomes (PROs)
The Australian EAFToS study is examining real-world ofatumumab use through secondary use of data from a digital patient support program (MSGo). At treatment initiation, ofatumumab 20 mg is administered by subcutaneous injection at weeks 0, 1 and 2, followed by maintenance dosing (20 mg qmonthly) starting at week 4. A preliminary EAFToS analysis reported that early adherence to this regimen was >97% (Van Der Walt et al. BMJ Open Neurol 2023;2705). Similar results were presented at ECTRIMS-ACTRIMS 2023 (Van der Walt et al. P746). An updated analysis with a larger dataset (n=662) has now been presented (Hardy et al. ACTRIMS Forum 2025;P420). A high persistence rate on therapy was maintained at 365 days (82%) and 730 days (74%) after treatment initiation. Treatment adherence was >80%, with most patients (94%) successfully self-administering the medication.

A separate analysis from the EAFToS II substudy (n=100) examined patient-reported outcomes (Van der Walt et al. ACTRIMS Forum 2025;V422). The rate of treatment discontinuation at one year was low (3%). Treatment satisfaction ratings at six months increased from baseline for Global Satisfaction (68.52 to 72.37) and Effectiveness (67.44 to 70.18), and were stable for Convenience (87.92 to 87.15). Patient-reported work productivity scores showed improvements in absenteeism, presenteeism, work productivity lost and activity impairment items. Quality of life and fatigue scores remained stable at six months.

Effect on cortical lesions
The effect of ofatumumab within the CNS has not been adequately explored. There is some preliminary evidence that ofatumumab indirectly reduces microglial activity in deep grey matter (Singhal et al. AAN 2022;S14.008). A Swiss study also found that anti-CD20 agents may have a modest impact on leptomeningeal inflammation, which is associated with increased cortical demyelination and neuroaxonal damage (Friedli et al. Mult Scler 2023;29:63-73).

A 7T MRI study examined changes in cortical lesion burden during one year of treatment with ofatumumab in a real-world RRMS cohort (N=16) (Zurawski et al. ACTRIMS Forum 2025;V228). Mean age was 39.6 years; mean disease duration was 3.0 years. All patients had cortical lesions (mean 8.1) at baseline, 38% had >1 thalamic lesions and 81% had leptomeningeal enhancement (LME). At one year, all patients were free of relapses, new T2 or Gd+ lesions. EDSS scores remained stable (mean 1.6 to 1.2) and T25FW times were essentially unchanged (4.8 to 4.7 seconds).

The cortical lesion burden was stable in 94% of patients after one year of treatment (0.18 to 0.19 mL). The LME foci number was unchanged in 75% of patients. There was a small increase in thalamic lesion number (0.8 to 0.9) and burden (0.01 to 0.02 mL). The percentage brain volume change was low at 1 year (-0.2%). The authors concluded that initiating ofatumumab may partially stabilize cortical and thalamic lesions and LME. Further studies are needed to characterize the impact of ofatumumab on grey-matter demyelination and leptomeningeal inflammation.