When the patent of reference natalizumab (Tysabri) infusion ran out the makers brought out subcutaneous natalizumab (Tysabri) and encouraged the neuros to switch…It also allowed generic makers to make replicas of natalizumab, called a biosimilar because it isn’t identical. Along came the first biosimilar natalizumab (Tyruko) and NICE in their stupidity said switch every one from the more expensive reference natalizumab to the cheaper version.
If you have been driving a Range Rover and you are given a Ford Fiesta and told to drive it. Would you be happy? If you have never had a car and are given a Fiesta you would you complain. Anyway biosimilar and reference natalizumab are not the same as they are made in different ways but they both do the same thing and block alpha4 integrin on lymphocytes and monocytes (macrophages of the blood) and stop them entering inflammed brain tissue. Although there was a clinical trial indicating that the two were comparable, news reports of unhappy people, notably in West London, indicated that the biosimilar was not as good as the original and wanted to switch back. In East London there was not the same level of complaint, I am told. However, it is right and proper that this is investigated and so there will be lots of real work studies. The NHS is well positions to get a view from across the country but this paper is from the Netherlands.
Gelissen LMY, Strijbis EMM, van Oosten BW, de Jong BA, Veldkamp AI, Rispens T, Killestein J, van Kempen ZLE. Safety and patient experiences with the natalizumab biosimilar in multiple sclerosis treatment. Mult Scler Relat Disord. 2026;109:107147.
Highlights
•Switching from originator to biosimilar natalizumab does not change trough levels. (So the levels of drug at the end of the cycle are the same…so they should be working in a similar way)
• Some patients reported more side effects after switching to the biosimilar (Similar to the West London effect some people are not happy and notice more side-effects).
•Lower patient-reported treatment satisfaction was observed with the biosimilar. (Similar to the West London effect some people are not happy to be on the new agent. I wonder how well the neurologists and nurses talked about the switch before doing it..What was your experience was this explained well before it was done).
•Discrepant JCV results with the new assay may complicate biosimilar use. (The assay created by the biosimilar company detects more JCV virus positiviity. As they have copied advice from the manufactures of the original product who did a lot of work to make the drug safer to reduce risk of PML and set levels based on their assay. The maker of the biosimilar copied the lable/summary of product characteristics and so set the value of positivity to start or stop giving drug. As the assays provided by the two copies are not equivalent there are differences when low levels of a JV virus response is detected. Because of the risk mitigation efforts put in place when the first assay was developed the biosimilar company will never get the samples (people developing PML) to really set the levels for their assay. What a mess).
There is another big f-up with other assays being different and I will explain this tomorrow.
Introduction: In 2023, the natalizumab biosimilar Tyruko® was approved for relapsing-remitting multiple sclerosis. Here, we assessed patient experiences and natalizumab serum concentrations in a real-world cohort of patients who switched from the originator, Tysabri®, to the biosimilar. Furthermore, we evaluated the consistency of the new John Cunningham virus (JCV) assay that comes with the biosimilar.
Methods: Patients, aware of the switch, completed questionnaires and had natalizumab concentrations measured during treatment with both products. Questionnaires assessed impact of MS symptoms, treatment satisfaction and wearing-off symptoms. An additional questionnaire assessed perceived differences or side effects with the biosimilar. JCV results of the new ImmunoWELL assay were analyzed over time.
Results: Among 83 patients, 15% reported more side effects during treatment with the biosimilar. Overall satisfaction was lower during treatment with the biosimilar compared to the originator. Other questionnaire scores and trough concentrations did not differ significantly. JCV results of the ImmunoWELL assay remained mainly consistent.
Conclusion: While most patients perceived the biosimilar as equivalent to the originator, overall satisfaction was lower, and some reported more side effects. As these findings differ from blinded approval trials, a nocebo effect may influence patient perceptions in real-world settings when switching from originator to biosimilar natalizumab.
Nocebo is an effect when you know you didn’t get the treatment and you experience adverse effects due negative expectations or suggestions, when there is no difference between the two. They say “two non-scientific articles published by The Guardian and Independent described a notable increase in patients who experienced side effects and even relapses following the switch from originator to biosimilar natalizumab. Possibly, informing patients about the switch in medication brand may induce a nocebo effect, negatively influencing their perception of the biosimilar. Given the non-blinded design of our study, this effect may also have been present in our cohort and could explain why some patients experienced more side effects with the biosimilar. However, disclosure of a switch in medication brand reflects routine clinical practice. Therefore, patient-reported outcomes from real-world cohorts are likely more representative of what can be expected when switching to the biosimilar, irrespective of the potential contribution of a nocebo effect. Moreover, the nocebo effect may not account for all newly reported symptoms”.
In the paper there was an example of a side-effect that disappeared after the switch-back.
This was a mess in the UK created by NICE by making people switch based on cost to NHS. When they next did the mandate for change this was only for newly people treated so they did not have to switch, but just start on the more cost effective (for the NHS) alternative…So they seemed to be learning from their mistakes. I suspect education is also part of the deal. Maybe in future the manufacturing process will need to be copied so the antibodies are generic not biosimilar.
COI: I had dealings (non-financial) with both manufacturers of natalizumab about a different safety issue (One was helpful the other was not)
Disclaimer: My views
Source: multiple-sclerosis-research.org