Loss of circulating antibody as a result of continuous B cell depletion is a risk factor for infection. The battle grounds to distinguish between the different anti-CD20 has been centred on loss of IgG. It has been suggested that ofatumumab does not induce as much loss of antibody as ocrelizumab. Indeed if you look at the data after 5 years in the trial there does indeed seem to be more loss….however there was a protocol difference and as soon as IgM dropped below normal there was a stop to allow the antibody levels to recover to limit IgG loss. Generally IgM is the first type of antibody made before there is IgG is produced from the IgM producing cells. So was it a fudge?.
Now as I say you can’t have it both ways and if it is true that there is less IgG hypogammaglobulin, then it suggests that that there is less B cell depletion, not in the blood, but perhaps in the spleen and the bone marrow where alot of B cells reside. I could buy this because there is alot less ofatumumab reaching the blood than happens with ocrelizumab. You have to give alot more ocrelizumab to maintain the depleting effect for 6 months compared to one month for ofatumumab.
However the real World data presented here says they are just as bad (or good) as each other for causing loss of antibody. Now one has to say that this is not a head to head trial but they tried to match characteristics. However, although there was no significantly different for the loss of antibody levels in people treated with ocrelizumab compared to ofatumumab, there was a significant difference in the number of serious infections (9.2% versus 3.4%) as a surrogate for loss of antibody mediated protection from infection. I think this is also reflected be effects on vaccination, suggesting a consistent biology. I will put some meat on these bones
Sangha KS, Jakubecz C, Maynard M, Hernandez RS, Esmaeili S, Zabeti A, Abboud H, Serra A, Woodson S, Obeidat AZ. Real world predictors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab or ofatumumab for the treatment of multiple sclerosis: The REPLACE-MS study. Mult Scler. 2026 Feb 9:13524585251412125.
Introduction: Ocrelizumab (OCR) and ofatumumab (OFB) are disease-modifying therapies (DMTs) for multiple sclerosis (MS). Patients on these DMT’s are at higher risk of hypogammaglobulinemia (HGG), which may increase the risk of infections.
Objectives: To investigate the impact of OCR and OFB and patient-specific, independent factors in developing HGG and serious infections.
Methods: This multicenter, cohort retrospective study included patients who had received induction dosing with OCR or OFB. The primary outcome was the incidence and predictors of HGG.
Results: A total of 911 patients (732 OCR, 179 OFB) were included. The mean (±SD) age was 45.4 (±12.8 years), and 68.6% were female. A total of 9.8% of patients developed HGG. Univariate analysis associated older age, Caucasian race, longer time on therapy, and lower baseline immunoglobulin G (IgG) levels as potential risk factors for HGG…..Age ⩾50 years (p = 0.039), Caucasian race (p = 0.0002), and time on therapy ⩾3 years (p = 0.0094) as independent risk factors for HGG. Eight percent of patients experienced a serious infection….HGG, lymphopenia, time on therapy ⩾3 years, previous DMT use, and progressive phenotype as independent risk factors for serious infection. Matching analysis found no differences in HGG and serious infection rates between OCR and OFB.
Conclusions: Age over 50, Caucasian race, time on therapy 3 or more years were risk factors for HGG.
COI: multiple
Disclaimer: My views
Source: multiple-sclerosis-research.org