Th17 are a menace and must be stopped?

T

Eksin MA et al. Secukinumab in the treatment of psoriatic arthritis or ankylosing spondyloarthritis with multiple sclerosis: a case series with literature review. Immunotherapy. 2022. doi:10.2217/imt-2021-0128

Plain language summary Background/aim: Multiple sclerosis (MS) is a central nervous system disorder, with rare cases reported to have associated spondyloarthritis (SpA) spectrum disorders such as rheumatic disease of the backbone and psoriasis-related rheumatic disease. The aim of this study is to evaluate the effectiveness of the drug secukinumab in the treatment of MS and accompanying rheumatic disease of the backbone and psoriasis-related rheumatic disease. Materials & methods: In addition to four cases of their own, the authors conducted a systematic literature search. Demographics, the presence of other diseases, symptoms of MS and SpA, medical treatments and changes in clinical and laboratory findings with treatment were recorded. Results & conclusions: After secukinumab therapy, all patients were found to have treatment response, without any progression of MS observed. For both SpA spectrum diseases and MS, secukinumab may be an appropriate choice.

Why is this important? Well it suggests that T cells are a useful target….there was a treatment response!

I was once at a MS meeting to debate that B cells and not T cells were important targets in MS, so even if I wanted to accept that B cells could activate T cells, within the debate I was forced to take the more extreme view. I was taken to task by some people who did not accept my view that Th17 inhibition was not particulalry great. They told me how good Th17 inhibition was, as it is all T cells, based on unpublished trial results. How can I argue against this as I have never seen it, so I looked a right Charlie in front of the audience as a cat had got my tongue. In this study they find people wth MS who also have rheumatic disease that is treated by anti-interleukin 17 (secukinumab) and report that there is benefit. I was not questioning that interleukin 17 inhibition was active in MS. Indeed in MS this antibody was tested in a trial and it reduced the level of gadolinium lesions by about 67% compared to placebo (Havddova et al. J Neurol 2016 263:1287).

Great you say no wonder I was taken to task. Indeed the results of mouse studies are used to support studies.

Today, I had some students to talk to about the value of animal studies in finding MS drugs and showed some successes and some failures. Anti-IL17 was seen as a success in animal EAE, but actually it was seen as a failure in MS and it was not developed by the manufacturer.

So I got some students to put their hands in the air if they thought a 67% inhibition was good and they all had their hands in the air. Then I said beta interferon-1a inhibited gadolinium lesions by 67% compared to placebo (Li & Paty  Annal Neurol 1999: 46:1972). Their hands were still raised as we hadn’t done MS drugs yet and they didn’t know how good beta interferon is. Then I said ocrelizumab reduced gadolinium enhancing lesion by 94-95% compared to B interferon (Hauser et al. New Eng J Med 376:221) and their hands came down. I then showed then some resullts from animal studies and asked then what they thought of the data and asked them if they would try it in MS after seeing this.

The darker symbols represent the IL-17 inhibitor.

The authors of the paper said ” we conclude that IL-17 is crucially involved in the cytokine network as an effeector cytokine in EAE”…Translated meaning IL-17 is a badass and needs inhibiting:-)

Now you have to answer does this pass the “smack you in the eye test. I said you have to read the graphs/data and not the text

COI Multiple

Disclaimer: This represents the views of the author and not an instituion

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MouseDoctor

6 comments

  • So it seems to me that EAE as an animal model of MS is essentially useless and needs to be replaced. Are there any better candidates?

  • Using Mouse words its all about treatment response(in case of b cell depleting theraphies)

    In this case we have t cell depleting theraphies and guess what you have also a treatment response
    So maybe just maybe there s a signal there

    Question: Why not use anti cd 20 and anti il-17 together?

    Combination theraphies are all to use nowdays in cancer theraphy

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