Importance of upper limb function in advanced multiple sclerosis

Alison Thomson, Gavin Giovannoni, Monica Marta, Sharmilee Gnanapavan, Benjamin Tumer, David Baker,
Klaus Schmierer

BartsMS, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary
University London, and 2Barts Health NHS Trust, Emergency Care & Acute Medicine, Neurosciences
Clinical Academic Group

Address: 4 Newark Street, London E1 2AT. g.giovannoni@qmul.ac.uk

Background: The recent emphasis on earty disease modifying treatment (DMnof people with MS
(pwMS) has consolidated the concept that once pwMS enter an advanced stage ("progressive MS") their
MS does not respond to existing DMTs. Results of the natalizumab (Nz) in secondary progressive MS
(ASCEND study, NCT01416181) challenges this concept. Although ASCEND's primary outcome was
negative, pwMS treated with Nz were significantly less likely to develop confirmed progression at 12
weeks when using the 9-hole peg test (9HPT) of upper limb (UL) function.

ObJectives: To present results of a online survey of pwMS exploring their views on the importance of
UL function to maintain independence.

Methods: Using an infographic and the BartsMS blog (www.ms-res.org), a social media platform for
pwMS with over
6,000 hits/day, we asked pwMS to rate the importance of UL function, and whether pwMS who are
dependent on a wheelchair for mobility should be excluded from clinical trials of DMTs. The
importance of UL (compared to lower limb) function was assessed using a Likert scale from 0 (UL
function unimportant compared to walking) to 10 (UL function critically important, i.e. more important
than walking in terms of staying independent).

Results: There were 130 responses to the survey. Sixty-nine respondents (53%) chose the maximum
score on the Likert scale, and 117 respondents (90%) selected a score of 7 or greater thus ranking UL
function well above lower limb function in staying independent. Ninety-five percent of responders
felt that pwMS in wheelchairs should not be excluded from future progressive MS trials.

Conclusions: pwMS overwhelmingly consider UL function as superior compared to lower limb

function in terms of staying independent. Results of the ASCEND trial suggest that worsening UL
function in pwMS may be modifiable even at an advanced stage of the disease, indicating new trial
designs based on this new evidence as well as the needs of pwMS are warranted. The discrepancy
between apparent lack of effect on lower limb function but positive effect on UL function in
advanced MS suggest greater functional reserve for the latter over the former.

Conflicts of interest: Gavin Giovannoni has received compensation for serving as a consultant from
AbbVie, Bayer Schering Healthcare, Biogen, Canbex, Eisai, Elan, Five Prime Therapeutics, Sanofi-
Genzyme, Genentech, GlaxoSmithKiine, Ironwood Pharmaceuticals, Merck-Serono, Novartis, Pfizer,
Roche, Synthon BV, Teva Pharmaceutical Industries, UCB and Vertex Pharmaceuticals.David Baker
has received research support from Sanofi-Genzyme and is founder, shareholder and consultant to
Canbex Therapeutics. David Baker has received research support from Sanofi-Genzyme and is
founder, shareholder and consultant to Canbex Therapeutics. Klaus Schmierer is the PI on trials
sponsored by Novartis, Roche and Teva and is involved in trials sponsored by Biogen, Genzyme,
BIAL, Cytokinetics and Canbex. He has received speaking honoraria from, and/or served in an
advisory
role for, Biogen, Novartis, Teva, Merck Inc. He was supported by Genzyme to attend AAN 2014 and
Novartis to attend
AAN 2016. He has received research support from Novartis, Biogen, National MS Society (US), MS
Society of Great Britain & Northern Ireland, RoyalCollege of Radiologists, and Barts Charity. Ben Turner
has received compensation for serving as a consultant from Biogen, Sanofi-Genzyme, Merck-Serono,
Novartis, Roche. Sharmilee Gnanapavan
has received travel grants from Teva and Novartis, and consulting fees from Genzyme and Novartis.
Monica Marta has received travels grants from AbbVie, Novartis and Biogen.