Don’t Get MS under control and you lose Brain!

WBV = whole brain volume

This is the extension study of ocrelizumab when people who had taken beta interferon were switched onto ocrelizumab and compared to ocrelizumab. You can read what the medical writer, drafted for the authors, I mean drafted in response to the input from the authors:-).

You can have a read, but the important point is this the brain volume lost in the 2 years of being put on beta interferon compared to ocrelizumab was still there after 3 years of every one being on ocrelizumab. So what’s lost is lost. Time is brain and so make sure you get on an effective treatment as quickly as possible after disease onset. Therefore, I am not sure we should be celebrating those people accredited with the trial design, so I hought I would give their names a miss., to test their new drug against agents that they know will not work well for the people volunteering for the trials.

I am sure they work well for some people

Medical writer et al. Five-years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension [published online ahead of print, 2020 Jul 20]. Neurology. 2020;10.1212/WNL.0000000000010376.

Objective: To assess over 3 years of follow-up, the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA studies in relapsing multiple sclerosis.

Methods: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN) β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression/improvement (CDP/CDI), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), and percentage brain volume change were analyzed.

Results: Of patients entering the OLE phase, 88.6% completed Year 5. The cumulative proportion with 24-week CDP was lower in patients who initiated OCR earlier, vs patients initially receiving IFN β-1a (16.1% vs 21.3% at Year 5; p=0.014). Patients continuing OCR maintained, and those switching from IFN β-1a to OCR attained near complete and sustained suppression of new brain MRI lesion activity from Year 3 to 5. Over the OLE phase, patients continuing OCR exhibited less whole brain volume loss from double-blind study baseline vs those switching from IFN β-1a (-1.87% vs -2.15% at Year 5; p<0.01). Adverse events were consistent with past reports and no new safety signals emerged with prolonged treatment.

Conclusion: Compared with patients switching from IFN β-1a, earlier and continuous OCR treatment up to 5 years provided sustained benefit on clinical and MRI measures of disease progression.

Classification of evidence: This study provides Class III evidence that earlier and continuous treatment with ocrelizumab provided sustained benefit on clinical and MRI outcomes of disease activity and progression compared with patients switching from IFN β-1a. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in OLE.

Clinical trial identifier numbers: NCT01247324/NCT01412333.

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  • -1.87% over 5 years = 0.374%/year on ocrelizumab which is not as good as alemtuzumab, natalizumab or HSCT.

        • Maybe but you hae to compare like with like and until you do I think you will find they are similar, do a trial from diadgnosis and lets see.

      • Prof G,

        It didn’t seem that long ago that B cell depleters were the way forward and the best thing since sliced bread. Of course MS (the real MS) always gets the last laugh. What sort of timeframe are we looking at to get therapies in to the clinic which address smouldering MS? Does the smouldering follow a fire, or is there just smouldering without an initial fire? There’s some chicken and egg stuff which I can’t get my head around.


        • Yes I have the same thinking about the chikcken an egg idea. Do you think we can avoid smouldering MS if we have flipped the pyramid (with ocrelizumab) very early ? (I remember that the average age of people in the OPERA study was like 37 so you have a lot of people in the study that have had the desease for more than 10 years since diag so I imagine smouldering ms might be bigger for them). What do you think ?

        • It is age-dependent. Physiological or normal brain volume loss starts at about 35 years of age and is about 0-15-0.2% per year up to 55 years of age then it speeds up as a result of ageing. Most pwMS in these trials are less than 55.

          • So because I am 30 I am supposed to have near 0% BVL ? I guess ocrelizumab is not that great but I cannot have HSCT or Alem in my country so ocrelizumab was the best I could have at front (still EDSS 0 and no cognitive problem so I hope I will be fine…).

        • Hi Bart’s Team, Can brain volume be monitored using standard MRI scans or do you need some special kind of MRI scan?
          When I ask my neurologist about monitoring brain volume I’ve never really gotten a satisfactory answer on whether he can do it or not, never mind an answer on the actual amount of volume loss going on. Would it be fair to say BVL is the best MRI market of smouldering MS?

  • Did this study have sufficient equipoise? Hasn’t it been known for years that 1FN B-1 does bugger all reduce atrophy?

      • I work in clinical research and I’m becoming increasing disillusioned with ethics committees (and Pharma companies both big and small).

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