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Serious Infections Requiring Hospitalizations

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    Serious Infections Requiring Hospitalizations

    Serious infections were defined as infections which required hospitalizations in a Swedish study of 6241 patients on various MS DMTs. The two paragraphs below in quotation are comments made on the study by Dr. Gavin Giovannoni regarding the anti-CD20 therapy, Ocrelizumab (Ocrevus).

    The anti-CD20 therapy reported on in the study was rituximab. However, infection rates are similar between rituximab and ocrelizumab, slightly higher with ocrelizumab. Therefore, it is legitimate using rituximab as an indicator for ocrelizumab's infection rates.

    Quote. "The overall figure is 2.24 serious infections per 100 patient-years. In other words, for every 45 patients on ocrelizumab for 12 months 1 patient will be admitted to hospital with a serious infection.”

    “However, if you develop low IgG levels (hypogammaglobulinaemia) the risk rises to 5.48 serious infections per 100 patient-years or for every 18 patients on ocrelizumab for 12 months 1 patient will be admitted with a serious infection. This is why we are now monitoring peripheral blood immunoglobulin levels on an annual basis in all our patients on anti-CD20 therapy.” End Quote

    The study Giovannoni commented on...

    Gustavo et al. Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol. Published online October 7, 2019. doi:10.1001/jamaneurol.2019.3365

    Dear Kris in Montana and Kathy Pennstater,

    This is the data I expected would come in perhaps 5 years on Ocrevus, but hoped never would at all. Now you know why I have been urging extreme caution and thoughtfulness in those contemplating leaving Tysabri for Ocrevus.

    At the time my spouse switched DMTs I was not aware of the extent of devastation on the immune system anti-CD20 therapies can have. This data clears up a lot of the sheer BS and hype that Ocrevus is a DMT requiring less monitoring. NOT AT ALL!!!!!!

    This is turning out to be a DMT which will require every bit as much study and monitoring as Tysabri and with time, IMO, even more monitoring and much, much more treatment for secondary problems (infections!) than Tysabri.
    I have been reading reams of physician-targeted material on immunoglobulin deficiencies which is something, that IMO, nearly everyone on Ocrevus will encounter and have to deal with if they stay on Ocrevus long enough. It is complex, it is nuanced and it will be a royal pain in the --- staying on top if it all.

    For example, here are some guidelines respective of dealing with immunoglobulin deficiencies. People on Ocrevus should keep an eye on their bloodwork to see if they fall in that category. Listen, all BS aside, the simple truth is that if anyone stays on Ocrevus long enough, the chance they will become Ig deficient is very high. Look at your blood work and understand the values, is my counsel.

    BTW, this is treated with IVIG which most tolerate well, but not all. My unprofessional opinion is that after a few years on Ocrevus IVIG treatment will be permanently required for many on Ocrevus.

    Guidelines for immunoglobulin deficiencies...

    "The patient and the patient's family should be taught how to recognize early signs and symptoms of infection so that the patient may obtain treatment as early as possible.
    The patient should be advised to avoid crowded places and people who have active infections.
    For patient education resources, see the Pneumonia Center, Lung and Airway Center, and Asthma Center, as well as Bacterial Pneumonia, Bronchitis, Asthma, Sinus Infection, and Myeloma.
    A common data pool has been established in Europe as an Internet-based database for clinical and research data on patients with primary immunodeficiencies in order to facilitate epidemiological analyses, development of new diagnostic and therapeutic strategies, and the identification of novel disease-associated genes."


      I am going to discuss this with my neuro again on my next visit.

      Myoak with this new report, are you more concerned about your wife even though she is having her CD20 monitored?
      God Bless Us All


        Thanks Myoak. I had asked my new neuro a little about it, as his PA accidentally put CD19 and CD20 on my bloodwork for Tysabri monitoring. He mentioned it was an area of study for those on Ocrevus.

        I had agreed with my last neuro and my current neuro that since JCV negative still, MS stable, and Tysabri safety profile better understood, I was staying put on Tysabri. Glad both neuros are aggressive with treatment, but only when warranted.
        DX 01/06, currently on Tysabri


          Originally posted by REG53 View Post
          I am going to discuss this with my neuro again on my next visit.

          Myoak with this new report, are you more concerned about your wife even though she is having her CD20 monitored?

          “However, if you develop low IgG levels (hypogammaglobulinaemia) the risk rises to 5.48 serious infections per 100 patient-years or for every 18 patients on ocrelizumab for 12 months 1 patient will be admitted with a serious infection."

          So, with low IgG one person out of 18 on Ocrevus will be admitted to the hospital to be treated for a serious infection versus 1 out of 45 with IgG in normal range. Normal range for an adult is 700 to 1,600 mg/dl.

          To me, both of those figures are high infection rates and both are substantially higher than with other MS DMTs.

          Yes, it is concerning. And, if there is a way to even possibly lower the risk of infection, I prefer trying.

          That possibility is the reason behind blood testing and dosing based on certain markers, especially CD19 (CD20) and IgG. CD19 has a reference range of 40 - 380mcl. If CD19 has not re-populated the reasoning seems weak (to me) to keep getting doses of a medicine likely to deplete IgG which fights infections.

          My spouse's latest test showed showed CD19 below 9 (very low) and IgG over 900 which puts it solidly in the 700 - 1600 range. IMO, that is kind of a sweet spot and with those numbers she did not receive a regular six month infusion.

          The first question is... will her MS be as controlled? So far, there is no change. Nor do I expect change as long as the CD19 remains low but only time will tell.

          The next question is... how long will it take for her CD19 to re-populate? No one can say because each person does so in a different length of time. Usually, it takes somewhere from 6 months to 4 years but even if it is 10 months, that is certainly significant, IMO. Not only from the standpoint of cost but more importantly from a health perspective.

          Recall the serious infection rate of 1 in 45 per year compared to 1 in 18 per year with diminished IgG. No one wants to be hospitalized with a serious infection if they could avoid it.

          Please be mindful that the consideration of dose extension with Ocrevus is far ahead of current clinical practice and you would need a fairly progressive neuro to consider it as an option. Certainly, there are a few out there, though. And talking about it with your neuro can only help.

          Ocrevus is an effective MS medicine.

          It is also important to note, so far, what we see is more fatigue and more serious infections on Ocrevus than Tysabri.


            Data worth downloading and discussing with your doctor:


            One of the things I noted is the average reduction 32mg/dl of IgG per year each of the first 6 years. The LLN (Lower Limit of Normal) for IgG is 565mg/dl.

            Some selections:

            “Within the first 6 years (288 weeks), treatment with OCR reduces serum IgG concentration at an average rate of –0.32 g/L per year (–3.0% per year)”

            Characteristics and outcomes of Sis (Serious Infections) associated with low Ig levels

            Urinary tract infections, cellulitis and pneumonia were the most common serious
            infections associated with Ig levels <LLN

            − This is similar to overall SIs in patients with MS treated with ocrelizumab
            − This is also consistent with types of serious infections observed in MS registries1–3
            • Most SIs associated with Ig levels <LLN:
            − Were of Grade 3 (69.1%). No fatal outcomes or opportunistic infections were observed
            − Resolved without sequelae (92.6%), within the expected clinical course (78.5% lasted
            <28 days) by using standard-of-care treatment
            − Resulted in no action taken (dose not changed) with ocrelizumab (87.7%)


            At approximately 6 study years (288 weeks) of ocrelizumab exposure:

            1.Rates of serious infections remain low and consistent with rates of infection-related hospitalisations in real-world MS cohorts.

            2. A reduction in serum Ig levels is observed, at an approximate mean rate of 3–4% per year for IgG, but for the majority of patients Ig levels remain above LLN

            3. There is an apparent association between decreased levels of IgG (and less so for IgM or IgA) and serious infections, but overall incidence is low

            4. The majority of serious infections following episodes of drop in Ig levels <LLN were urinary tract infections, cellulitis and pneumonia; most resolved with standard of care, and in most cases patients remained on treatment with ocrelizumab


              Thank you...

              I have my first Ocrevus infusion next week. I am very early in this process, but I am going to discuss monitoring with my doctor. Obviously, I am not several years into this, but I would like to discuss with her before my 6 month infusion.
              Diagnosed RRMS 4/7/15, symptoms for 8 months prior. Copaxone 4/27/15



                Ocrevus is Orelizumab


                Quote “If you buy into the mantra that a B cell therapy only works on B cells, then think again. Like a debutante three years shy of their first season, successful targeted therapies in the immune world are disappointing to say the least, and most definitely fall short of initial expectations.”

                “Ocrelizumab a humanized monoclonal antibody targeting CD 20 on the surface of B cells during their development, was the first to capitalize on this.

                Later on it became apparent that a small set of T cells also expressed CD 20.

                Not neutrophils, however.

                Neutrophils are the most abundant immune sub type and are your first responders against invading microbes.”

                “Whether, late-onset neutropenia is a self-limiting adverse event and doesn’t require the discontinuation of ocrelizumab remains to be seen…” End Quote