The drug class being used increasingly are the anti-CD20 depleting drugs. There are more and more of them. So which do you choose? They all target CD2O and they are all based on human IgG1, but are they the same?
The battle for the sales team is how they position thier drugs to get maximal uptake…
The simplest way to get uptake is to do a deal with Poundland NICE to give them a cheap product to save UK plc money…However for a marketeer that is disaster…If your product is viewed as cheap then it can be perceived as been less good compared to the more expensive agents…Do you want a robin reliant or a Porsche?
Likewise you can always be undercut
For natalizumab there has been uproar as people are being offered and asked to switch to the cheaper version.
So one way is the extol virtues of the agents and I can see this happening in the CD20 world.
They should not diss the competitors but can say mine does this…you can then fill in the blanks
The easy one is subcutaneous at home or infusion in hospital, but we are seeing formulation changes so that the formulations are changed so there is more than one variant that can be given under the skin.
There is the dosing frequency monthly or every six months but as doctors meddle this blurs things
But there are difference suggested e.g. time to repopulation anti drug antibodies, levels of antibody loss, which equates to infection risk.
I am trying to understand these, to work out if they are real of imagined
All are similar as they are all designed to kill B cells and keep them out of the blood so they can’t get into the brain, but they are different. This is the battle ground for the marketeers.
We know that the Swiss are famous for being chocolate makers, are they also good at making fudge. When comparing drugs you have to understand that things are not reported to the same level. For example one drug is reported to take 25 weeks to repopulate whereas others take 70 weeks so if you want to stop drug to get pregnant and have B cells there could be a perceived benefit well one is reported for time taken to get to 40 cells per microlitre and others to 80. It is obvious if you going to take longer to get to 80. However, if you are dosing every six months then you are giving enough so that the effective dose is maintained for six months or so. The first month there is more than enough to do the job. You also have to understand what comes back after you stop, the drug is not the same as was there before drug…..
However on feature is the wearing off effect. We had a post a week ago on this and so I guess worms are being placed in people’s brains that this is a difference between drugs.
It says it is present and goes within a week after the dose but I don’t really get it. Comparing ocrelizumab and rituximab I can understand as they are both dosed at 6.monthly intervals but ofatumumab is monthly so if you get the message that the wearing off occurs a week before and lasts a week after says it is only any good for two weeks…So it is not a comparison. However the individual data shows that for ofatumumab over 80 percent of cases occur a week before dosing but for ocrelizumab is it about 60 percent occurs more than 4 weeks before
So there is more detail in the actual paper fatigue and imbalance are the most common reported issues that become evident and seems to be to be a consistent phenomena suggesting there is a biology to uncover.
Fernandes AA, Correia C, Barreto B, Ferro D, Seabra M, Mendonça T, Soares Dos Reis R, Guimarães J, Abreu P. Exploring the wearing-off phenomenon among anti-CD20 therapies in multiple sclerosis. Mult Scler Relat Disord. 2025;105:106846. doi: 10.1016/j.msard.2025.106846. Epub ahead of print. PMID: 41265013.
Introduction: The wearing-off phenomenon, characterized by the re-emergence or worsening of symptoms prior to the next scheduled dose, may affect people with Multiple Sclerosis (pwMS) receiving anti-CD20 monoclonal antibody therapies. This phenomenon can negatively influence patients’ functional status and perception of disease control.
Objectives: To assess the prevalence, clinical characteristics, and potential risk factors associated with the wearing-off phenomenon in pwMS treated with ocrelizumab, ofatumumab, or rituximab.
Methods: We conducted a cross-sectional cohort study involving 139 pwMS followed at a tertiary care center and undergoing treatment with anti-CD20 agents. Participants completed a structured questionnaire to identify symptoms suggestive of wearing-off.
Results: Among the participants, 94 (67.6 %) had relapsing-remitting MS and 45 (32.4 %) had progressive forms. Patients were treated with ocrelizumab (51.8 %), ofatumumab (33.8 %), or rituximab (14.4 %). The wearing-off phenomenon was reported by 43 patients (30.9 %), most commonly presenting with fatigue (86.0 %) and balance disturbances (37.2 %). Symptom onset occurred more than one week before infusion in 67.4 % of cases, with delayed resolution (>7 days post-infusion) in 46.5 %. Most classified symptoms as moderate to severe, with notable functional impact and increased anxiety in 65.1 %. No significant differences in prevalence were observed among the three drugs. Wearing-off was more frequent in females (p = 0.046). Among males, higher body weight and body surface area were initially associated with the phenomenon but did not remain significant in multivariate models. No associations were found with BMI, age, EDSS, or treatment duration.
Conclusion: Wearing-off is frequently reported across anti-CD20 therapies, though its subjective nature and lack of biomarkers present challenges for targeted management strategies
Source: multiple-sclerosis-research.org