Are all anti-CD20 the same?
They all target the the same molecule i.e. CD20 binding due to the front end of the antibody and all have the same basic back end (Human IgG1) and all of them deplete the memory B cells. However, how they do this is different. How they are used and dosed is different.
There are lots of different antibodies that target CD20 but in the UK there are three that are approved for use in MS. Ublituximab, Ocrelizumab and Ofatumumab…Elsewhere there is rituximab as an World Health Association MS essential mecidine used alot in Scandiland.
They are biologically different but the question for the marketeers is how do they sell their product. What are the differences?
You can have infusions every 6 months in hospital or you can get it under the skin monthly at home….so there is the choice. You go for convenience?
But is it your convenience? Are you gaslighted by health care professionals to select things of their choice?
If everything was equal and you had free choice perhaps you would expect that use of anti-CD20 antibodies to be the same across the country or even across a city. But I can see that this is not the case and so the answer to the question “Are you being gaslighted” the answer must be “yes” as the prescribing patterns are not the same (Secondary Care Medicines data).
The use of anti-CD20 antibodies is increasing, because these are the only high efficacy, rapidly active, first line treatments that have limited monitoring requirements. Simply they work and are easier to use than some other antibodies. For example where blood tests may be needed every month. The lazy neuro won’t want to do that especially if they are not paid to do it and perhaps the greedy neuro who can bill for procedures would.
Poundland NICE-UK now says use the cheapest treatment.So if may not be gaslighting for their benefit but for the benefit of UK-PLC.
There are reasons to select the different anti-CD20.
Some hospitals don’t have enough infusion chairs/nurses so they are going to want to avoid infusions…..ofatatumumab (or perhaps subcutaneous ocrelizumab) here we come…Some places don’t want the hassle, so every one will be offered ofatumumab, which can be given at home. Some places may want the cash associated with infusions and so will offer infusions, so historically, ocrelizumab is used. Now there is competition there with the introduction of ublituximab.
There may be other reasons such as how quickly you want the treatment to work or there may be safety reasons. These thoughts have been fed largely by the information provided by the pharma companies to inform the neuros. However, information can give companies a market edge. If I look at each agent I can think how one could give information
One battle ground is the effect and consequence of long-term depletion of B cells. If you can’t make new B cells you will not produce the antibodies that can help you fight infection and so loss of circulating antibody called hypo(lower) gammaglobulin (antibody) aemia (in the blood). This is associated with an increased risk of severe infection. It can be so severe that you need replacement antibody therapy to protect you from infection. The first line of defence is IgM production and this isfollowed by IgG
If you look at the trial data, as I did, it is evident that one antibody seems to cause less hypogammaglubinemia of Immunoglobulin G than the others and that is ofatumumab.
So at baseline there is about about 10g/L of antibody after two years of ublituximab , ocrelizumab or ofatumumab there is still 10g/L IgG, but after 6 years it is down to 8-8.5g/L for infusion antibodies reflecting that some will have dropped below the lower limit of normal. The companies have been helpful giving me data presented at meetings, which are not easy to find to build up a picture and an argument
So maybe a marketing oppertunity to get space between the products not only keep people out of your hospital so save the VAT (Tax) and reduce risks of infection… a no-brainer
Spread the word and educate neuros about loss of circulating antibody.
Who would do that?
Have a read it’s free. Check out the conflicts….but I will say no palms were greased:-)
Gnanapavan S, Kang A, Baker D, Giovanonni G. Clinical opinions and case studies on understanding and managing hypogammaglobulinaemia in multiple sclerosis: United Kingdom perspective. Mult Scler Relat Disord. 2025;96:106353.
Anyway I presented the data on the antibody levels (above) and a clinician stood up and says these was fudge used to create the data because when there was a drop in IgM (or IgG) levels the trial protocol dictated that the treatment be stopped until the antibody levels increase above the lower limit of normal so the IgG levels would not drop. The early IgM levels dropped so they were the same.
So was this shrewd planning because the marketeers knew about the risk of loss of antibody with long-term us of ocrelizumab as the drug was in the market years before ofatumumab arrived and this risk was known because it was seen with rituximab that was approved years before that.
Now data was presented at ECTRIMS 2025 that if you look at the people who took ofatumumab and exhibited low levels of IgM and did not stop at 5 years, the conclusions are not that different. So the original idea could still hold.
However, trial data eventually gets replicated by real World data and this data (below) suggests that there is no real difference in loss of antibody levels between ofatumumab and ocrelizumab so the idea of a difference is perhaps just a load of **llocks
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; 32:338-346.
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. Multivariable regression identified 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. Multivariable regression identified HGG, lymphopaenia, time on therapy ⩾3 years, previous DMT use, and progressive phenotype as independent risk factors for serious infection. A propensity-score-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.
Whilst I suspect any differences in loss of circulating antibody is perhaps marginal as they all deplete IgM levels by the same amount and the fudge would certainly help prevent loss of antibody levels….as I always say “you can’t have it both ways” so if it was not causing as much loss of circulating antibody, it would suggest that the antibody is not as depleting.
So before the knowledge of the fudge, the ferret in me, started to investigate so the biology could be supported. I have to say there are elements of biology that support that conclusion. The maximum level of circulating antibody is about 100-200 times less because you inject once a month under the skin verses every 6 months directly into the blood. The antibodies are not going to clear the spleen and the bone marrow until they reach the blood. If it goes under the skin it has to go through the lymphatics to drain into the blood in the arm pits and most of what is injected never reaches the blood. As a consequence of this there will be more rapid repopulation….look at the trial data ofatumumab repopulates after 24-25 weeks ublituximab and ocrelizumab after about 70 weeks. But another fudge I did spot because the level of normal was half the level used by the other companies that use standard definitions of 80 cells per microlitre not 40!. For ocrleizumab there is data showning it takes 50 weeks to get to 40 weeks. To get depletion for 6 months you have to give alot more antibody rather than the 20mg ofatumumab for monthly injection. Ocrelizumab depletes at 600mg (typical dose given every six months) but also depletes at 20mg but as about half of the antibody disappears each month 600mg injection simplistically gives 300mg a month later then 150mg (2months later) then 75mg (3months later) then 37.5mg (4months later) then 18.75mg (5 months later). So after 5 months there is still enough antibody to kill any B cells, so 20 weeks after stopping it is still doing the same job and cells will only return once it stops working so 50 week repopulation from stopping with ocrelizumab isnt that different from stopping with 25 weeks with ofatumumab. However because you have to give more at the start it means it can get more places. Spill a cup of tea on a carpet see where it goes, spill a pan of tea on the carpet it will go further.
No I dont think it matters. That is to say you don’t need to clear you the bone marrow and spleen as long as you stop B cells getting into the brain. Likewise do you need to get the antibodies into the brain. If the maxium circlulating level of antibody in the blood is 1 microramme per thousandths of a litre of blood (a mL) and antibody is 99.9% excluded from the brain that means a maxium of 1 nanogramme per ml gets in the brain which is perhaps too low for the antibody to do much especially when killing molecules and cells have to get into the brain to make the antibody work?
That’s another story.
COI Multiple
Disclaimer My views
Source: multiple-sclerosis-research.org