Rocky Mountain Ritixumab Fever


This is the real life experience of a single centre in the USA. As you can see their experience with CD20 depletion was essentailly as good or better to other commercial products,

Rituximab versus natalizumab, fingolimod, and dimethyl fumarate in multiple sclerosis treatment.Vollmer BL, Nair K, Sillau S, Corboy JR, Vollmer T, Alvarez E.Ann Clin Transl Neurol. 2020 Aug 6. doi: 10.1002/acn3.51111.

Introduction: Limited comparative effectiveness data for rituximab (RTX) versus natalizumab (NTZ), fingolimod (FTY), and dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS) exist.

Methods: Clinician-reported data on patients prescribed RTX, NTZ, FTY, or DMF for the treatment of MS at the Rocky Mountain MS Center at the University of Colorado were retrospectively collected. Outcomes included a composite effectiveness measure consisting of clinical relapse, contrast-enhancing lesions, and/or new T2 lesions, individual effectiveness outcomes, and discontinuation. Logistic regression was used on patients matched by propensity scores and using average treatment effect on treated doubly robust weighting estimator.

Results: A total of 182, 451, 271, and 342 patients initiated RTX, NTZ, FTY, and DMF and were followed for 2 years. Before and after adjustment, the odds of experiencing disease activity was significantly higher for FTY [adjusted OR (aOR) = 3.17 (95% CI: 1.81-5.55), P < 0.001].and DMF [aOR = 2.68 (95% CI:1.67-4.29), P < 0.001], and similar for NTZ [aOR = 1.36 (95% CI:0.83-2.23), P = 0.216] versus RTX. When examining months 6-24, NTZ demonstrated higher odds of disease activity compared to RTX [aOR = 2.21 (95% CI: 1.20-4.06), P = 0.007]. Similar odds of discontinuation were seen between NTZ and RTX [aOR = 1.39 (95% CI: 0.88-2.20), P = 0.157]; however, FTY [aOR = 2.02 (95% CI: 1.24-3.30), P = 0.005] and DMF [aOR = 3.27 (95% CI: 2.15-4.97), P < 0.001] had greater odds of discontinuation than RTX.

Interpretation: RTX demonstrated superior effectiveness and discontinuation outcomes compared to FTY and DMF. Although RTX demonstrated similar effectiveness and discontinuation compared to NTZ, RTX had superior effectiveness during months 6-24 and fewer discontinuations when excluding discontinuations due to insurance issues. Results suggest superiority of RTX in reducing disease activity and maintaining long-term treatment in a real-world MS cohort.

Serious safety events in rituximab-treated multiple sclerosis and related disorders.Vollmer BL, Wallach AI, Corboy JR, Dubovskaya K, Alvarez E, Kister I.Ann Clin Transl Neurol. 2020 Aug 6. doi: 10.1002/acn3.51136. Online ahead of print.PMID: 32767531

Introduction: Studies investigating rates and risk factors for serious safety events (SSEs) during rituximab treatment of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and related disorders are limited.

Methods: Rituximab-treated patients with MS, NMOSD, or related disorders at the Rocky Mountain and New York University MS Care Centers were included. The follow-up period was defined as the time from the initial dose of rituximab up to 12 months of last dose of rituximab or ocrelizumab (in patients who switched). Clinician-reported and laboratory data were retrospectively collected from electronic medical records.

Results: One-thousand patients were included comprising 907 MS, 77 NMOSD, and 16 related disorders. Patients had a mean follow-up of 31.1 months and a mean cumulative rituximab dose of 4012 mg. Of the 169 patients who switched to ocrelizumab, the mean ocrelizumab dose was 1141 mg. Crude incidence rate per 1000 person-years (PY) for lymphopenia was 19.2, neutropenia 5.6, and hypogammaglobulinemia 17.8. Infections resulting in either hospitalization, IV antibiotics, or using antibiotics ≥14 days occurred at a rate of 38.6/1000 PY. Risk factors for infection were duration of therapy, male gender, increased disability, prior exposure to immunosuppression/chemotherapy, lymphopenia, and hypogammaglobulinemia. Particularly, wheelchair-bound patients had 8.56-fold increased odds of infections. Crude incidence rates of malignant cancer were 3.5, new autoimmune disease 2.3, thromboembolic event 3.1, and mortality of 5.4 per 1000 PY.

Interpretation: Rates of SSEs in patients with MS, NMOSD, and related disorders were low. Through properly assessing risk:benefit of B-cell depleting therapy in neuroinflammatory disorders and continual monitoring, clinicians may decrease the risk of serious infections.#

COI multiple but non-relevant

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  • Thanks MD, interesting article. In pursuit of fairness, do you think 2 years is long enough to ascertain efficacy? Given there is 2 year therapeutic lag? I noticed they did not compare with dmt titana like caldderbine and Alemtuzumab. Also, there’s no details of demographics of the patients in the groups. Again this really a pointless trial and proves nothing because of the design of the trial. They needed to first ensure those being compared are at the same point in diagnosis to treatment and ensured the trial ran for sufficient time to compare brain atrophy. Interesting trial but leaves more unanswered questions and does not prove or disapprove anything to make meaningless conclusion. MS research is truly in a mess. Why doesn’t fda or ema set clinical trial standards before they are allowed to run. But not shooting the messenger, just the message.

    • I suspect this wasn’t a prospective clinical trial, but a department that started collectIng clinical data on an electronic platform 2 years earlier. It may be the consequence of Brandi Vollmar needing publications to progress her career and fishing the retrospective data. Within these data there were probably results for Cladribine, Ocrelizumab, etc. and these were excluded due to publication bias or the intention to get a multiple subsequent publications from the same work to buff her CV.

    • You are correct 2 years is a short time, but this is the duration of many trials. It isnt a trial but real-life data.

      • Why isn’t anyone allowed to reply to the comments below anon 11.30? If its by barts team I salute the person. I know which side my bread is buttered. Or is it bait meat?

    • My opinion is that more clinical data like this should be gathered and published.

      While anyone can poke holes at the crudeness of the metrics and methods, these are what many/most good clinicians are using to steer the course of their MS patients today.

      Sure you could ask for BVL or NFL or retina scans or measurements of functional loss… But how many people have these measured today on a regular basis ?

      This kind of analysis and review is what all MS centers should be doing. If the data were gathered in a more standardized fashion more patient results could be aggregated.


      Trying to figure out what is good vs what is rubbish is the key.
      Many people have conflicts of interest in keeping this information from end users.

      Probably some MS drugs are so ineffective that they should not be prescribed for most patients.

      The BARTS team does a pretty good job in trying to bring light to these best practices.

      I applaud this effort. Let’s see more good clinical data from all over the world and more thought to how to gather good records without making more work for the neurologists and their teams.

      • I totally agree with you on this. As a patient when you get asked to give input on what drug to choose there is a dearth of information that provides useful drug comparisons. This is a start in the right direction despite its faults.

        • My problem isn’t with studies or any clinical trials. My problem is with badly designed studies and trials that are pointless because they do not conclusively prove anything. So you are saying based on this study your are going to ask for Ritixumab? Its not even available on NHS. Sorry Anon 11.38 like the article your comments are completely pointless. The point of studies and trial is to advance understanding. This is as Mark said written with hidden agenda. Shame on the person who carried out this study.

          • I get what you are saying. There are loads of badly designed trials.

            But I think this was not really originally designed as a formal trial.

            Probably some bored researcher who was COVID constrained, decided to analyze existing patient data, and try to see what was working for patients and what was not.
            They probably did not spend a lot of money.
            I mean other than the patient’s money who pay ~10K$- 100K$ per year for treatment.

            This is the real world data. It probably won’t result in any earth shattering news or major MS research breakthrough.

            But clinical data if gathered routinely, methodically, and using the best biometrics widely available, can give very valuable feedback. It can show what works and what does not work for real patients. If this was done for thousands, or hundreds of thousands of patients, patterns in effective care would become more transparent. These records were taken. They should be looked at, organized, and published.

            I think that this is the kind of analysis that most neurologists are sorta-kinda keeping as a recordbook in their own mind. What works what does not. What they hear at conferences and from their buddies and the sales reps who bring in lunches, pay for seminars…

            I am not a doctor, I am not a researcher, I am a person with MS. I want to know what works. I don’t want to use a powerful drug that will hurt me if it does not have a good chance of providing benefit. I want to use the best drug for my phase of this disease.

            I DON’T KNOW WHAT THAT IS.

            This kind of data is useful to help decision making.

          • Agree it is not a trials they are looking at their own service and making conclusions…I dont need to to trials to make similar ones but as you say this is real life data

          • This was a retrospective study so no need to criticize the “clinical trial design”. Very useful to analyze existing data and frankly, very cost-effective.

      • I agree
        “Probably some MS drugs are so ineffective that they should not be prescribed for most patients”…I wonder what you meant :-).

        • From reading this blog, I am starting to get a clearer picture.
          The ones that sound like CRAP, and scuttle in the sand with weak and ineffective pincers.

          But I am just a patient with MS, not a real expert so take my opinion with a grain of salt…

          My only COI is my health…

  • Hello MD, with regards to Heidi’s point – why is the full picture not given when choosing, or should I say trying to pick a less side effect med, easy to take & administer, availability, funding given, efficacy & oh should I mention patient’s age & other comorbidities to take into consideration – then to read Dr Google & his infamous followers of tried, it & this happened or tried it, and this seemed to protect me from progression according to my MRI but my MS was still active daily! And lastly, I have been free of full progression for x amount of years & am still taking it – so it has worked hasn’t it!?!

    If the CD20 therapy along with others are so effective at holting MS – surely all the above should be plain sailing! I’ve had my first full dose of CD20 therapy – & I seem to have had quite a few minor in medic’s eyes but not so minor in mine – when you’re trying to get on with life! Who wants to hear about those infections & as a patient battling the current NHS crisis with back appointments – you start to become quite cynical & obviously you worry that the therapy isn’t being recorded properly – no-one has asked ‘how am I getting’ although I will say I have my annual Neuro appt end of month – may be then I can spend the whole time complaining about the infections and never really discussing my MS!

    I advocate, treatment to stop the inflammation causing you your symptoms & stop you feeling like rubbish everyday! Inflammation is the current problem with COVID leaving its mark – could we look into now more, that the whole world is too. MS may get better support & it might be somewhat related in terms of treating the inflammation of the lungs – could the inflammation of the nervous system & brain – be where the research & funding could be partially directed!

    • “why is the full picture not given when choosing”…This is where you have to do your reading, but this is where you would pick subcutaneous cladribine using profKs dosing schedule (COI I’m an offlable Clad lad), but joking aside you would conclude that there are only 1-3 drugs worth thinking about and you would not bother with the rest. I suspect many neuros have not got the jajce to say this. Registries like MS base can get a glimer of what happens in the real world… are having a go at Prof Vollmer but is this any different from MSBAse, NACROMS, MS register

          • Thanks for the reply MD. I wasn’t being lazy. I have spent a good few hours/days trawling this blog, which is a great resource. Where I was unclear was on whether you were placing HSCT in your champions league, meaning one of the other top shelf would drop into the qualifying round. I have not seen an article that definitively sets this out and to be honest, I was trying to avoid going down a rabbit hole of PIRA and smouldering MS, which, whilst hugely informative, is slightly depressing reading as an Ocrevus patient. Unless you advise otherwise, I will take annon 12.31’s answer, which gets me straight into the group stages at least

    • Drug effficacy varies from patient to patient. But I agree with MD if you want to make sure as much as possible your ms has stopped then alemtuzumab, ocreliszumab, Natlizumab and caldribine are the only choices. Clay walker the country singer has been neda for 18 years by just taking the old injectable. Do really does depend on your biology.

        • Damn it. Why is there so much ambiguity in MS. Not sure what to believe. Err may be poorly designed studies and trials? But sounds strange if MS is a immune mediated disease once the immune attacks you why would it then forget?

  • For Anon 12.21. I understand what you are saying. The problem with researcher led investigations the influence of bias in trial design. However, you make a very good and clever point. The data does not need 5o be collected but already exist in IT based systems used by Care providers. Given we already have a centralised registry called MS Registry. All that is needed is a direct api to load MRI data to central location/Azure database. Then run machine learning against the data. This will be earth shattering research and I will bet all my money it will lead to a cure FOR MS. Technically this can be done in weeks with right IT savvy people. Just wandering why this hasn’t been done/thought of before.

    • Given we already have a centralised registry called MS Registry. All that is needed is a direct api to load MRI data to central location/Azure database…in some cases signing up to the MS register links to the NHS record in other cases this is not the case.

      Run machine learning…and hey Presto…As I said to another reader today try reading Hans Christian Anderson if you want real fairy tales:-)

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