AAN 2021. Ocrelizumab overdosing?

A

Why was ADIOS a no brainer?…..Perhaps because it was going to work!

ProfG with a non-fully functioning, non-productive brain can see the logic of ADIOS, hopefully you can see the value of ADIOS, but can other Neuros see it? In some instances I’m afraid not…..I did a debate to young neuros and had my ass-kicked by my opponent. I gave them more data than you can shake a stick at, but they didn’t buy it.

It reminds me of the Joke what’s the difference between a Neuro and Neuro machine….you only have to punch the information in once…OK its a drummer joke for a Drummer and Drum machine but you get the frustration.

So where are we?….This week is AAN week

The corporate news, or should I say probably corporate news to be safer, as it is about the trials delivered by the usual MS B cell expert.

206 – B-Cell Subset Depletion Following Ocrelizumab Treatment in Patients With Relapsing Multiple Sclerosis
MS expert

Background: B cells play a pathogenic role in MS, with certain B-cell subsets (memory, plasmablast/plasma cells) elevated in cerebrospinal fluid (CSF) vs blood. B cells, including those in CNS lymphoid aggregates, have been implicated in chronic inflammation potentially responsible for disease progression. OCR depletes CD19+ B cells in blood and CSF, reduces CSF IgG synthesis, and reduces disease activity and progression in patients with RMS.

Objective:To assess the impact of ocrelizumab (OCR) treatment on blood B cells and B-cell subsets in patients with relapsing multiple sclerosis (RMS) from the OPERA I (NCT01247324) and OPERA II (NCT01412333) trials.

Emmmmm. As published in OPERA and ORATORIO (Supplementary data) in 2017…that’s 4 years ago….CD19 B cells in the blood are depleted out of sight….So what do we think will happen to the CD19, CD20 B cells that make up this population?….Speculation alert (Hold on to your bowels if it frightens you)....Me thinks these cells will be inhibited.

We know this happens with rituximab and essentially the same happens with ocrelizumab because we reported that Baker et al. 2020 based on 2012 data from the phase II clinical trial. But it seems the information doesn’t exist until it is shown by an MS Expert and remember the Jobbing Neuro does not have time to read and like to get their info from experts at Neuro meetings.

Design Methods:Total B-cell (CD19+) and B-cell subset (mature naive [CD19+/IgD+/CD27−], memory B cell [CD19+/CD27+/CD38low], double-negative memory B cell [CD19+/IgD−/CD27−] and plasmablast/plasma cell [CD19+/CD27++/CD38++]) levels were measured via flow cytometry in whole blood samples in 1,645 RMS patients at study baseline and before each OCR infusion (weeks 24, 48, 72, 96). Median cell count (cells/μL) was calculated across timepoints, and the proportion of patients with median B-cell count below the lower limit of quantification was assessed for each B-cell subtype across treatment arms and mean OCR exposure quartiles (measured as mean OCR concentration over treatment duration).

Results. Total B cells and all B-cell subsets were significantly depleted by OCR (pCD19+/CD27++/CD38++ cells, mainly plasmablasts in blood, had the lowest relative reduction, and mature naive B cells had the greatest.

Conclusions:Ocrelizumab treatment induces a significant depletion of all B-cell subsets measured, with CD19+/CD27++/CD38++ cells reducing the least, likely representing plasmablasts with low/absent CD20 expression. Greater ocrelizumab exposure, as well as repeated dosing, was associated with greater reduction of all B-cell subsets.

So no big surprises, except one and that is….No real mention of memory B cells. I suppose it is all so complicated and I guess we don’t want you to speculate and to think about them. As it might get you thinking that they may be dosing too frequently. Mature B cells, which make up about 70% of the peripheral blood B cell pool get hit the most and guess what plasmablasts and plasma cells that do not really express CD20, so they will escape depletion…..Yep it means no good antibody response when infected or vaccinated for COVID-19 as these are made by mature B cells. But if you have made an antibody response it should remain. Therefore, start COVID-19 vaccination before starting anti-CD20 if you can. If you can’t whilst on active treatment don’t expect a good antibody response after the COVID-19 vaccine. So we have no idea what B cells do in MS….Remember folks keep Happy Campers (neuros) in the dark and feed them on mushroom food, that way Happy Campers stay happy;-(.

Whilst we are on trials news we have

203 – Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis. MS Expert

Background:Ongoing safety reporting is crucial to understanding the long-term benefit–risk profile of ocrelizumab in patients with multiple sclerosis (MS). Safety/efficacy of ocrelizumab have been characterized in Phase II (NCT00676715) and Phase III (NCT01247324; NCT01412333; NCT01194570) trials in patients with relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS).

Results: In clinical trials, 5,680 patients with MS received ocrelizumab (18,218 patient years (PY) of exposure) as of January 2020. Reported rates per 100 PY (95% confidence interval) were: adverse events (AEs), 248 (246–251); infections, 76.2 (74.9–77.4); serious AEs, 7.34 (6.96–7.75); serious infections, 2.01 (1.81–2.23); malignancies, 0.46 (0.37–0.57); and AEs leading to discontinuation, 1.06 (0.92–1.22). As of April 2020, over 158,000 patients (Ker-Khing. This is alot of dosh from sales, why wouldn’t you want to keep dosing forever?) with MS have initiated ocrelizumab globally in the post-marketing setting. Data remain generally consistent with those observed in clinical trials.

Conclusions: AE rates in the ocrelizumab all-exposure population and post-marketing settings remain generally consistent with the controlled treatment period in RMS/PPMS populations. Serious infection and malignancy rates remain within the range reported for patients with MS in real-world registries. In patients with RMS and PPMS, ocrelizumab demonstrates a consistent and favorable safety profile, and these longer-term data are in accordance with the safety outcomes initially observed during the controlled treatment periods. Regular reporting of longer-term safety data will continue.

So there you have it….. all is safe and lovely, no worse than having nothing. Don’t worry I don’t understand patient years either. But I guess it means that for one person on a drug for 2 years, this is 2 PY. So if you had 100 people on drug from a year (10 on drug for 10 years) you would have 2 serious infections. This is great unless you are the person with the serious infection then it is not quite so re-assuring

Rituximab and ocrelizumab were born in an era when neuros didn’t know how they worked. The knew they killed B cell expressing CD20 and the object was to wipe them out of sight for ever. They knew that the most B cell in the blood disappeared for at least 5 months, but a few had returned by 6 months. So let’s dose ever 6 months….I understand this.

But you an I know that for many this is overkill and when you get your six monthly dose there are no B cells in the blood to kill. This is why infusion reactions disappear after the first doses. You get a reaction when the B cells are being attacked and liberating their contents as they die. So it is the effect of B cell guts that are causing it.

Fast forward for at least 4 years and we are still dosing a 6 monthly intervals, where we (OK a royal wee as the Experts still think it is so, so complicated) have a working mechanism of what the CD20-depleting antibodies are doing. They are killing cells within the memory B cell compartments (If writing a paper I would be forces to say it also kills CD20 T cells) and that is getting rid of MS and cells in the immature/mature compartments are going to give you new responses. But we need trial data for change. ProfG is doing his DoDo (Double Dose) trial and has not enough energy for ADIOS….So it is probably ADIOS to that idea….Until the Americans/Italians Do it. Maybe a way to say adios to ADIOS was by saving the DoDo (Double dose).

Maybe ProfG has a real cunning plan and is laying ground work as a Double Dose of Ocrelizumab means the antibodies will hang around for at least an extra half-life and you will definately have to dose less than every 6 months:-)….It sort of depends on your target. Relapses verses Progression. Anyway I digress

ADIOS is a trial design to examine an extended dose interval and immune-reconstitution. It could have 4 arms the standard of care (ocrelizumab every 6 months. This is don’t rock the boat approach), an arm when you dose when CD19 levels re-appear (The extremely..No brainer, cautious approach); you dose when defined CD19, CD27 levels appear….This has been done in about 6 conditions including MS and is likely to work based on biology and a more limited set of data. The biological approach ) or you could dose for a year (minimum of 3 doses) and watch and wait for MRI activity like you would with alemtuzumab and then see if ocrelizumab is an immune reconstituion therapy and perhaps 50% of people wouldnt need further dosing (For neuros and some people the scary approach). I would say ideally you want to match the CARE-MS trial design and treat at diagnosis. Here there is less data but offers the best gains. However, ProfG thinks that some Neuros think it is too much of a risk. At present we only have the rituximab experinece and the data from the phase II study. This is published in Baker et al 2017, Baker et a. 2020. To their credit the manufacturers have given us access to the data and the data in Baker et al. 2017/2020 was not based on a complete data set but was based on data lock 2012. They have given us access to data lock 2016 (n=50 per group (4 groups) completed to 18 months post dosing) but I can’t tell yet due to contractual obligations.

If you want to dose when the B cells recover then you would not be dosing every 6 months for most people as we know that for most people they stay depleted for longer than 6 months. Now if I said no brainer from the neuros because they don’t seem to be able to read and assimilate….hopefully the Association of Neurologists won’t come after me, but there is enough literature to suggest dosing at six monthly dosing is overkill . But the Neuros will say show me the data.

So I guess they can have it in AAN2021 stereo, as there are two identical studies below and were I guess caused by the delay in dosing due to te COVID-19 pandemic. I bet we will have it in surround sound as there are many more studies.

Dosing to B cells

For the left eye.

Elizabeth Padron, MD 010 – Trends and predictors of peripheral CD19+ B-cell repopulation in patients treated with extended interval ocrelizumab dosing during COVID-19 pandemic.

Background.Peripheral CD19+ lymphocyte (CD19L) count is a surrogate marker of therapeutic efficacy of anti-CD20 therapies. B-cell repopulation (defined as ≥1% CD19L of total lymphocytes) typically occurs at 9-12 months following rituximab infusion. It has been used to guide dosing-interval in patients with multiple sclerosis (MS) and rheumatoid arthritis.  However, ocrelizumab (OCR) has a fixed 6-month dosing-interval. Adjusting OCR treatment-cycle based on CD19L repopulation in clinically stable patients can minimize the risk of prolonged B-cell depletion. The aim of this study was to evaluate the trends of CD19L repopulation in patients treated with OCR at extended dosing-interval during the COVID-19 pandemic.

Objective:To assess the B-cell repopulation to guide time-to-infusion decision making in patients treated with ocrelizumab at extended dosing-intervals during COVD-19 pandemic.

Design Methods:This was a retrospective study of the timing of B-cell repopulation, defined as ≥1% CD19L, in patients who received OCR at extended dosing-interval during the pandemic. Data on age, gender, body mass index (BMI), disease duration, prior immunotherapy, duration of OCR, and timing of B-cell repopulation were collected. The predictors of time to repopulations were evaluated using bivariate and multivariate regression analysis.

Results:Twenty-seven (23 relapsing MS, 4 primary-progressive MS) patients (mean age 41±13 years, 79% women) were studied.  Mean CD19L repopulation was 238 ±92 days with significant inter-patient variability (159-539 days (5.5 months to 1.5 years). All patients remained clinically stable during the extended treatment-cycle. Time-to-repopulation was longer in patients with prior exposure to drugs with immunosuppressive properties compared to those without exposure (296 vs 226 days, p=0.03).  Age, gender, race, BMI and disease duration were not associated with time-to-repopulation.

Conclusions
In this observational study, CD19L repopulation latency varied among patients with MS; longer interval associated with prior exposure to drugs with immunosuppressive properties.  It may be possible to adjust ocrelizumab re-infusion interval based on CD19L repopulation in stable MS patients.

For the right eye

086 – Olivia Moswela, B-Cell repopulation after Ocrelizumab in Multiple Sclerosis Patients

Background. At the onset of the Covid-19 pandemic, there was uncertainty over the risk of infection and Covid-19 disease outcomes in pwMS treated with B-cell depleting therapy, namely ocrelizumab. Data is emerging from various global and national registries that exposure to ocrelizumab portends a more severe course of Covid-19. The implications of ocrelizumab exposure for immunisation when a vaccine against Covid-19 becomes available remain uncertain. In multiple sclerosis (MS), ocrelizumab is administered as a fixed 600mg dose at six monthly intervals (≈180days). Previous research indicates that there is inter-individual variability in time to B-cell repopulation after B-cell depletion therapies.  To balance the risks of suboptimal MS treatment against the uncertain risks of ocrelizumab during the pandemic, we offered B-cell depletion monitoring with the aim of ocrelizumab re-infusion when peripheral B-cells were detected.

Objective.To determine the time to B-cell repopulation after ocrelizumab infusion in people with multiple sclerosis (pwMS)

Design Methods. Prior to Covid-19, lymphocyte subsets were measured before each 6 monthly ocrelizumab treatment cycle. During the pandemic, we aimed to measure peripheral lymphocyte subsets at monthly intervals starting from the infusion due date. B-cell repopulation was defined as the first detection of CD19+ cell percentage of total lymphocytes >1% by flow cytometric analysis.

Results. Our cohort consisted of 32 pwMS. Out of a total of 48 treatment cycles, 15 demonstrated B-cell repopulation with the time to B-cell re-population ranging from 160 (22 weeks = 5.5 months) to 321 days (45 weeks = 11 months) . Two pwMS had a CD19+ cell count >1% prior to the 6 monthly infusion due date at 160 and 176 days (25 weeks = 6 months). Data collection is ongoing and will be presented when available.

Conclusions: Our data indicates that B-cell repopulation after ocrelizumab exposure demonstrates inter individual variability, as has been observed with rituximab. Monitoring of B-cell subsets prior to dosing could help identify and tailor dosing schedules to minimise risk of ocrelizumab exposure.

Therefore for the sake of 3/32 (6%) people you maybe overdosing 94% of people. You just have to read, to see It is possible because it has already been done in MS using rituximab…

This is a study from Oxford so at lesss than 6 months n=28/49 (not sure how many were looked at) but wait until until 7.5 months it is (11/49 = 80%) may some B cells…Would they make a COVID-19 vaccine response?

Image
Co Dr. Brandon Beaber @Brandon_Beaber Twitter Apr17

Dosing to memory B cell population

1-012 – Tailoring B-cells depleting therapy in MS according to memory B-cells monitoring: a pilot study
Giovanni Novi

Background
Phase II and III clinical trials revealed the potent suppressive activity on MRI activity and ARR of CD20 directed antibodies in MS. However, no studies to dissect the optimal infusion regimen have been performed. Infusion regimens with higher infusion intervals and lower drug dosage might maintain the same efficacy than current (fixed-dose) treatment schedule.

Objective
To evaluate rituximab (RTX) efficacy using a memory B-cell based reinfusion regimen, with a variable reinfusion cut-off, according to year of treatment.

Design Methods
This is a retrospective and prospective bicentric study including patients with MS treated with RTX. All patients were treated with rituximab induction, followed by maintenance infusion, according to memory B-cells repopulation. Predefined cut-off values for reinfusion (percentage of memory B cells among peripheral blood PBMC) were: 0.05% for the first two years of treatment, with subsequent doubling for each year of treatment

Results
101 patients were included in the analysis, 32 patients had a relapsing remitting phenotype, while 69 had a progressive phenotype.Mean FU was 1.75 years (range 0.29-6.56). ARR was 0.67 (95% Confidence Interval (CI): 0.53-0.85) in the year before RTX start and decreased to 0.02 (95%CI 0.004-0.04) during the whole FU. Proportion of patient with MS activity (i.e.: relapse or MRI activity) was 74/101 (73.3%) in the year before RTX start and decreased to 11/71 (15.5%) and 1/27 (3.70%) in the two years after RTX initiation.Annualized RTX infusion rate was 1.70 (95%CI:1.45-1.99), 1.41 (95%CI:1.09-1.80), 0.97 (95%CI:0.62-1.43) and 0.85 (95%CI:0.36-1.64) for the first four years after RTX initiation, respectively.

Conclusions
Results of this study show that memory B cells based RTX reinfusion protocol is able to reduce mean number of RTX reinfusion with persistent reduction of disease activity. A memory B cells threshold for disease activity recrudescence could be possibly identified with longer follow-up (and higher reinfusion cut-off).

Therefore if you dose to memory B cells within 3 years it is less than one a year required

Anyway more AAN data shows Ocrelizumab works on relapses

Maria Cellerino, 095 – Ocrelizumab treatment in patients with progressive multiple sclerosis: a single-center real-world experience

It works : At 1-year FU, MRI-inflammatory-activity-free survival was 87.3% (CI95%: 76.9-97.7%), relapse-free survival was 100% …….. We recorded 69 AE(adverse events) in 36 pts (patients) (32 upper respiratory tract infections; 6 herpes simplex-1 reactivation; 7 lower urinary tract infections; 1 acute myeloid leukemia following myelodysplastic syndrome; 1 appendicitis treated with surgical procedure). No serious infusion-associated reactions were reported.

099 – Recently Diagnosed Early-Stage RRMS: NEDA, ARR, Disability Progression, Serum Neurofilament and Safety: 1-Year Interim Data From the Ocrelizumab Phase IIIb ENSEMBLE Study. Timothy L. Vollmer, MD, FAAN

Baseline EDSS, 1.71 [0.95]; time since RRMS diagnosis, 0.36 [0.40] years; time since MS symptom onset, 1.10 [0.84] years) of which 74.6% had both MS relapse and MRI activity. At Weeks 24 and 48 most patients (91.2% [n/N=618/678] and 84.8% [n/N=545/643]) had NEDA. Adjusted ARR at Week 48 was 0.005 (95%CI, 0.003-0.009). EDSS score (mean [SD]) remained stable at Weeks 24 (1.56 [1.04]) and 48 (1.55 [1.07]). Age-adjusted serum NfL levels (geometric mean, pg/mL [coefficient of variance]) at baseline and Week 48 were 10.5 (107.8%) and 4.55 (59.5%), versus 4.12 (36.2%) in age-matched healthy controls. Safety results were consistent with prior studies.

Conclusions
Treatment-naive patients with early-stage RRMS in ENSEMBLE responded consistently well to ocrelizumab treatment based on clinical, MRI and biomarker measures; no new safety signals were observed.

However some diehards still want to convince you that is is all caused by T cells, but if you get rid of them for MS maybe you get rid of anti-viral responses, this is not what you want to hear in times of COVID-19

199 – Functional CD8+ T cell-specific Immune Response Alterations under Ocrelizumab Treatment
Vasiliki Pantazou, MD

Background/Administration of higher efficacy disease modifying drugs in multiple sclerosis patients is not without concern during the SARS-CoV-2 pandemic. Under ocrelizumab, an anti-CD20 antibody that causes depletion of circulating B cells with minor alleged effect on T cells, infections are generally mild, although the risk of both viral and bacterial infection is slightly increased.

Objective.To investigate the viral CD8+ T cell cellular immune response under ocrelizumab.

Design Methods. We performed repeated enzyme linked immunospot assays (ELISPOT) in a cohort of 37 ocrelizumab-treated MS patients, before treatment initiation (T0), and at 6 months (T6) and one year into treatment (T12). Viral antigens consisted in a pool of immunodominant 8-10 mer epitope peptides including epitopes of EBV, CMV, and Influenza. Further characterization of CD8+ T cell subtypes was done using mass cytometry. We corrected all data for age and total CD8+ T cell count using linear regression models.

Results. Of the 37 patients tested, 27 had positive ELISPOT assays at T0 while only 21 remained positive at T12. Although the total number of CD8+ T cells remained stable (p=0.117), the frequency of IFN-gamma secreting CD8+ T cells, among the responders, was significantly reduced in 51.5% of patients at T6 (p=0.002) and 55.2% at T12 (p<0.001). Furthermore, at T6 and T12, subpopulation analysis revealed a 22.7% reduction in memory CD8+ T cell numbers as compared to T0 (p=0.003), mostly due to a depletion of CD8/CD20 double positive T cells (frequency reduced by 68.8%, p<0.001) and an increase in numbers of naïve CD8+ T cells (23.4%, p=0.004). No correlation was noted with age at disease onset (p=0.366) or with age at ocrelizumab onset (p=0.174).

Conclusions. Although a minor component of the total pool of CD8+ T cells, the double positive CD8/CD20 T cells may play an important role in virus-specific cellular immune response.

Foot and Shoot springs to mind

217 – Ocrelizumab two-year real-world safety and effectiveness over in the treatment of multiple sclerosis
Enrique Alvarez, MD, PhD

Background
OCR, used in the treatment of multiple sclerosis(MS), is a monoclonal antibody targeting CD20, resulting in B-cell depletion.

Objective:To describe the patient two-year experience of MS patients treated with  Ocrelizumab(OCR).

Design Methods:100 randomly selected MS patients prescribed OCR prior to May 2018 at the Rocky Mountain MS Center at the University of Colorado were retrospectively followed two years from OCR start date. Lab data, relapse history, adverse events, MRI outcomes, disease history and patient characteristics were collected. Descriptive statistics were used to describe the sample group.

Results: Patients had a mean age of 44.3 years at date of first infusion; were predominantly female(76.0%); and had a mean MS disease duration of 10.8 years. Of the sample group, 82(82.0%), 16(16.0%), and 2(2.0%) were relapsing-remitting, secondary progressive, and primary progressive MS, respectively. Eighteen patients had switched from rituximab to OCR.  Two(2.0%), 1(1.0%), and 6(6%) patients experienced a clinical relapse, enhancing lesion and new T2 lesion, respectively. Twenty(20.0%) patients discontinued OCR at our center at <24 months. Nine patients were lost to follow-up, 7 patients discontinued due to insurance/cost issues, 1 patient discontinued due to adverse events, specifically hypogammaglobulinemia, and 3 patients discontinued due to other reasons, such as family planning and concern for cancer. During the first and second infusion course, 21(21.4%) and 9(10.2%) experienced an infusion reaction that interrupted the OCR infusion, respectively, and none experienced a life-threatening reaction or were hospitalized. After initiating OCR, 3 patients were diagnosed with basal cell carcinoma. Infections resulting in an emergency department visit or hospitalization occurred in 12(12.0%) and 2(2.0%) patients, respectively. Eleven(11.0%) patients experienced lymphopenia ≤500/mm3, and 2(2.1%) experienced neutropenia ≤1000/mm3. Seven(8.3%) patients experienced IgG levels ≤500, 30(35.7%) experienced IgM levels ≤40.

Conclusions:Our data suggests OCR is safe and effective in the treatment of MS. Additional data on an increased sample size will be presented.

245 – Recurrent MRI Activity After Treatment with Ocrelizumab for Multiple Sclerosis
Shamik Bhattacharyya, MD

Background:To characterize MRI activity during treatment with OCR in a clinical cohort.

Objective: Treatment with ocrelizumab (OCR) for multiple sclerosis (MS) is associated with 5% or fewer rate of new gadolinium (Gd)-enhancing lesions on MRI.

Design Methods: Retrospective review of MRI in patients with MS treated with OCR in the CLIMB cohort at Brigham and Women’s Hospital. Brain or spinal cord MRI was “active” with any of the following: (1) Gd enhancement (2) new restricted diffusivity of a lesion, or (3) new or enlarging T2 lesion compared to a baseline MRI acquired at or after start of OCR.

Results: There were 383 patients treated with OCR [68% female, mean age 48.4 (SD 12.3) years, median EDSS 2.5 (range 0-8) of whom 68% had relapsing-remitting, 21% secondary progressive, and 11% primary progressive multiple sclerosis. Final MRI was obtained average of 14.2 (SD 7.3) months after starting OCR. In total, there were 25 MRI relapses identified in 24 (6.2%) patients [23 new Gd enhancing, 1 new restricted diffusion, 1 new T2 lesion]. Patients with MRI activity were 63% female with mean age of 41.4 (SD 11.3) years, median EDSS of 3 of whom 79% had relapsing-remitting and 21% with secondary progressive MS. There were two distinct patterns of relapse. The predominant pattern was gadolinium enhancement or restricted diffusion of an old T2 lesion present prior to start of OCR. This pattern occurred in 14 MRI scans (6 brain, 8 spinal cord) acquired median 9 months after OCR start. The second pattern was new lesion formation, present in 11 MRI scans (8 brain, 3 spinal cord) obtained median of 5 months after OCR start.

Conclusions: The more common pattern of radiological relapse on OCR surprisingly was recurrent MRI activity at an old lesion site with predominance in the spinal cord.

Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.

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  • I gave them more data than you can shake a stick at, but they didn’t buy it.

    Its not their brains that are frying

    You have been saying this for so long this aproach is use in nmo ,why they dont get it?

    As of April 2020, over 158,000 patients

    = 10 744 000 000$

    Nice work

    Nice post

    • Maybe because people in power are not saying this….and they won’t unless pharma loses interest.

  • As if you were reading into my comments. This… This is the info that I have been looking forward to reading. ” Of course I’ve got my own personal experiences but I’m just one person jumping up & down (well in my mind I am jumping because MS took away my ability to jump without a bad outcome of falling on my face), so I have all these studies to arm myself with as my backup! I have to say though, At this point in my game of life, I feel like I am my own science experiment. And before I close out my comment, Mouse Doctor I am personally glad to see you back here writing in the blog. Thank you for taking time out of your busy day to write here & help share your knowledge with the rest of us. You are a very compassionate person who cares about MSrs & it shows….

  • Hi, after 2+ months after last 600mg dose of Ocrevus (my 4th full dose), I have 6% CD19+ cells percentage of total lymphocytes cells, which is the lowest value of normal (6-19), however total count of CD19+ cells is slightly under lowest value of normal 88,29 (100-500).
    Did you ever experienced such a quick repopulation?

      • I had problem with teeth, no other problems. About anti-drug antibodies I do not know, this is what I had idea also.
        Is there a way to find out from blood, is it common procedure?

        • You could ask your neurologist to ask Roche to test this, we (royal we…DrAngry) have the technology.

          • I will do, thx for this info.
            If there are anti drug antibodies against Ocrevus, is it for good, or could they disappear with time and Ocrevus take effect again?

          • I think that once there they are made it can be for life. But the important point is that with time they wane and because ocrelizumab will kill the B cells it is going to kill within a few hours it could do this before the ADA would come back. This is the pincipal with alemtuzumab over 85% of people have them but they fade and so you only dose for 3 not 5 days on second cycle. With natalizumab it has been reported that they can also drop over time, I am guess even whilst on drug

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