Anti-TNF therapy says MS is one disease


Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing-remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after treatment initiation, he developed slowly progressing neurological deficits including gait impairment, paraesthesia of the lower limbs, strangury and visual impairment, which led to the discontinuation of adalimumab therapy. Magnetic resonance imaging of the brain and the spinal cord revealed multiple inflammatory lesions and cerebrospinal fluid examination showed slight pleocytosis and positive oligoclonal bands. Thus, PPMS was diagnosed according to the 2017 revision of the McDonald criteria. As PPMS often causes only subtle symptoms in the beginning and early treatment discontinuation of anti-TNF-α therapy seems essential to improve the patient’s outcome, we think that it is important to increase the awareness of slowly progressing neurological deficits as a potential adverse event of anti-TNF-α therapy among all clinicians involved in the initiation and monitoring of these drugs. In addition, the occurrence of both RRMS and progressive MS upon anti-TNF-α therapy might suggest a shared TNF-α-mediated pathophysiological mechanism in the evolution of all MS subtypes.

If MS is one disease it is not surprising that anti-TNF therapy can be associated with PPMS and RRMS, being male and older at onset is a risk factor for developing PPMS. But what is the difference between MS and arithrits? I have a few ideas but that’s another post.

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  • Sorry if this is a silly question but , how can you discard completely that this person will have had ppMS even if he had not taken anti-TNF? Were there any scans taken before the TNF therapy ?

    • Good question. Did they have MS before. Yes this can’t be excluded but what you look for is unusual events after taking a drug, this is what a phase IV programme does after is approved. After people started taking anti-TNF on thing that occured more frequently was demylinating disease. Anti-TNF is also associated with more Lupus like issues too.

      • What about selectivity of blocking TNFR1 signals vs stimulating TNFR2 signals? It seems extremely difficult to parse the plus/minus signals coming from both receptors when the antibody therapies used to date in people bind TNF itself and don’t hit the receptors.

        • Yes there is a literature on the difference of TNFR1 and TNFR2 signals and as you say the antibody is removing TNF, so is this removing a survival factor. I am on record with a hypothesis about how TNF is central to the maintainence of B cell follicles. The question is will we be brave enough to go anywhere near TNF as a therapeutic target. Would you be willing to take a TNF inhibitor if i could explain why the past trials went wrong? I am not sure you would, but evidence would point towards TNF being a player in progressive MS.

          • I have more risk tolerance, but I am not the family member with MS. You would need better biomarkers to determine whether a treatment is going south and have them scheduled soon after treatment to catch exacerbation before it gets out of control. The pwMS whom demonstrated disease worsening on TNF therapy- was their monitoring extensive enough? Would that be scheduling oligoclonal band evaluations or MRI scans only a week after initiation of treatment?

            I gleaned my suggestion based on this review on TNF therapies, and it reads really well besides suggesting such specific TNFR1 and TNFR2 therapies. One TNFR1 therapy mentioned is anti asthma drug zafirlukast, and another is by GSK that has two single domain anti TNFR1 antibodies.

            A New Venue of TNF Targeting

            Sophie Steeland, Claude Libert, and Roosmarijn E. Vandenbroucke1,

            PMID: 29751683

  • This post must be for me….Lolllllllllllllllllllllllllllllll

    Bit unscientific conclusion


    Anti-TNF therapy says MS is one disease

    By the same token

    Multiple sclerosis following a spinal cord injury:
    a rare and unfortunate case

    It also proves that ms is one disease

    Come on you can do better than that

    You know(better than me) that you need a trigger in susceptible individuals (virus bacteria ,trauma etc)

    Can you infer that ms is one disease ? With that information?


  • Only one patient who developed PPMS? So what? Says nothing much to me. And I have PPMS without being male, old, or having any sort of anti TNF therapy. Or any therapy, come to that. So I’m a bit nonplussed. 🤔

    • For every risk factor, you find people who do not fit the profile and the risk of demyelination after TNF is a rare event. However it has to tell us something about MS and it implies that TNF is inhibitory in some way. One way we have suggested is that in some people and it results in an enhanced number of memory B cells. As we have shown all drugs that inhibit MS result in the depletion of memory B cells. So if we inhibit memory B cells we inhibit MS. We could make the arguement that more memory B cells are associated with activity of athritis. But there is a problem here. Our studies with anti-BAFF show that elevating memory B cells is not associated with disease activity.but anti TNF makes arthritis better in most people but in some people with MS it worsens disease so what is the difference.

      Is it that anti TNF antibody can get in the joint to inhibit arthritis but enough doesnt get into the brain because of the blood barrier, to inhibit MS.

  • I too think the distinction between RRMS, PPMS, SPMS is nonsense.

    But I highly doubt MS is actually the same disease in everybody. It’s like cancer.

    Lung cancer can be caused by smoking, by asbestos etc. The progression is basically the same in most people (for the sake of the argument, ignoring the different cancer types), but there are different causes.

    But whatever the cause, the illness presents itself a certain way.

    It’s the same with MS. The cause in most cases is most likely a combination of a viral infection and other genetic and enviromental factors (like other infections). But it’s not always the same for everyone. Some people get MS from EBV and C. pneumoniae, others from HHV-6 and C. perfringens and so on.

    That’s why there’s no black swan in sight, because there isn’t one. And that’s why treating MS as one disease will be exactly the same dead end as splitting it up the way it was done in the past.

    • I am suspect you are right…..years ago it was Devics MS sand then it became NMO and NMO became NMOSD, we have aquarporin 4 variant MOG variant. Ohow one verses many diseases is not about biology, it is about how you give people an opportunity to try a treatment for your own variant of the condition

      • I wonder how rare it really is. Is anyone investigating the prevalence of ms after antiTNF Therapy. I was out on an antiTNF after developing RA a few years ago. Six months later it was stooped due to lack of efficacy. Switched to Rituximab and had : episodes in 10 months. Brain and clonus lesion. Recent diagnosis of RRMS. How many more aren’t being picked up

  • Doesn’t Ibudilast have some anti-TNF properties? I believe it suppresses the production of TNF by glial cells, correct? Yet, it does show some indications of being a potential MS treatment. Interesting drug all around, suppresses glial cell activity, is an anti-inflammatory, has anti-pain properties, and is a vasodialator. Some signs that it may be neuroprotective as well. Any thoughts on this?

    • Yes it is an interesting one. It is a pde 4 inhibitor and is anti Tnf not just in glial cells although it failed in rrms there was an effect in progressive ms. We where asked to look at it ten years ago but weren’t keen as rolipram another pde4 inhibitor seemed to make ms worse. The UK tried to test this but the American sprint team had got in their first. Ibudilast also has actions on macrophages outside of the pde4 activity. I think it will be going into phase iii and maybe the legal wrangles will happen after that. It is an old Japanese anti asthma drug. The idea to try in ms is not inventive , but maybe patents weren’t filed when we were contacted about it.

  • I’m on weekly adalimumab injections for Crohns disease. I waited too long to seek treatment for my Crohns and around 60 percent of my small bowel was damaged. After getting a turbo charged boost of Adalimumab I have to take this stuff weekly. Long story short I’m getting some terrible side effects, namely fatigue, numbness, tingling, pain in my arms/legs, had spinal pain a few times too.

    Oddly enough I had a bad Crohns disease flare and spent the night with the most funky of numbness and visual problems. All over my body I was going numb(Would randomly jump from my arms, legs, abdomen etc) and my vision would go all funky.

    Had no issues prior to going on to Adalimumab. This stuff really is poison isn’t it? I’ve had enough of dealing with the funky neuropathic symptoms. I’m now making every effort to get an answer. I know it’ll take a while though.

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