Barts-MS rose-tinted-odometer – zero stars
I am in Milan at the International Progressive MS Alliance Industry Forum Meeting. The aims of the meeting are to:
- Discuss challenges understanding and measuring progression and its impact on drug labels
- Discuss regulatory issues, opportunities and implications for drug labels and regulatory approvals
- Discuss links and opportunities for industry and the Alliance to contribute feedback to the International Advisory Committee on Clinical Trials in Multiple Sclerosis activities on phenotype classification and clinical trials
- Share lessons from recent clinical trials/development programs and how they impact the challenges of developing drugs for progression in MS
I have been asked to speak on the implications of disease classification for drug development, regulatory approval and drug labelling. This topic is fine, but it is far removed from people with the disease, which is why I am going to base my talk on case scenarios to illustrate how absurd the current status quo is for pwMS and the wider MS community.
As a pre-read to these case scenarios, I suggest you read a previous post of mine about progressive MS.
Case scenario 1
48-yr old woman
MS x 22 year
Last relapse 8 years ago – lower limb weakness and exacerbation of bladder problems
Annual MRI scans:
Last scan 3 years ago
Marked brain and spinal cord atrophy
Poor gait, now needs to use walking sticks outdoors and can manage only 10-20m; uses scooter outdoors
Bladder and bowel problems with recurrent UTIs
Significant cognitive impairment
EDSS = 6.5
DMTs: Interferon-beta-1a stopped 3 years
Does this patient have active SPMS?
Does she have active SPMS?
Case scenario 2a
36-yr old male
MS x 12 years
Previously treated with Rebif-44 x 6 years; failed due to ongoing relapses
Switched to fingolimod 3 years ago
Last relapse 4 years ago / MRI stable
EDSS = 3.0 (stable)
Difficulty running and walking long distance; Fitbit data over the last 3 years showing objective reduction in daily activity
Does this patient have SPMS?
Is the patient eligible for a DMT switch?
Is the patient eligible siponimod?
Case scenario 2b
36-yr old male
MS x 12 years
Previously treated with Rebif-44 x 6 years; failed due to ongoing relapses
Switched to fingolimod 3 years ago
Last relapse 4 years ago / MRI stable
EDSS = 3.0 (stable)
Difficulty running and walking long distance; Fitbit data over the last 3 years showing objective reduction in daily activity
Labeled as having inactive SPMS
Under NHSE guidelines fingolimod is stopped and 10 weeks later he presents with new onset paraplegia
MRI shows longitudinally extensive myelitis and >30 new Gd-enhancing lesions over the neuraxis
Does this patient have SPMS?
Is the patient eligible siponimod?
What happens if his treatment response is suboptimal on spinoimod?
Case scenario 2c
36-yr old male
MS x 12 years
Previously treated with Rebif-44 x 6 years; failed due to ongoing relapses
Switched to fingolimod 3 years ago
Last relapse 4 years ago / MRI stable except progressive brain volume loss (0.78% per year over the last 3 years; Icometrix)
EDSS = 3.0 (stable)
Does this patient have SPMS?
Is the patient eligible for a DMT switch?
Is the patient eligible siponimod?
Case scenario 2d
36-yr old male
MS x 12 years
Previously treated with Rebif-44 x 6 years; failed due to ongoing relapses
Switched to fingolimod 3 years ago
Last relapse 4 years ago
EDSS = 3.0 (stable), but has noticed increasing forgetfulness at work and difficulty using a new software system
T25W & 9HPT stable
SDMT worsening:
2017 = 48
2018 = 45
2018 = 41
2019 = 39
Does this patient have SPMS?
Is the patient eligible for a DMT switch?
Is the patient eligible siponimod?
If you work through the logic of each of these case scenarios that are based on real-life examples you will quickly see that the current status quo is not compatible with the biology of the disease and makes very little sense; in other words, classifying MS as three diseases is absurd.
CoI: multiple