Subcutaneous immunoglobulins with rHuPH20 in multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is an immune mediated neuropathy that shows a
progressive asymmetric weakness of the muscles in the hands and arms and feet
to a lesser extend. The differntiation with fatal diseases as amyotrophic
lateral sclerosis (ALS) is for many reasons essential. One of the reasosns is
that for MMN there is a treatment consisting of repeated infusions of
immunoglobulins (IVIg). This does not cure MMN, but will reach stability to a
slow progression in weakness over many years. On average, patients get their
IVIg once every 2-4 weeks. Unfortunately in 20-40% of the infusions side
effects are seen, locally and systematically. Examples are headache, skin
reactions and gastro intestinal side effects. Usually this can be countered by
applying secundary medication, but the repeated character is very burdensome
for patients and affects their quality of life.
More recent subcutaneous immunoglobulins (SCIg) are available. This reduces
(probably by different pharmacokinetic properties) the side effects
and has in small clinical trials similar effects as IVIg.
A problem is the limited volume per infusion that can be given. To solve this
problem, a combination of medication (Hyqvia) is at hand. It consists of an
enzym e (hyaluronidase; rHuPH20) and immunoglobulins. rHuPH20 splices subdermal
structures creating space for larger volumes of SCIg.
This is already approved in immunodeficiency diseases and certain malignancies
(multiple myeloma and chronic lymphatic leukemia).
It is not known whether Hyqvia is effective and tolerable in MMN.

To study whether hyqvia is as effective, safe and tolerable (or more tolerable)
as IVIg.

Monocenter cross-over intervention study

IVIg is switched into hyqvia.

Burden:
3 times venapuncture
questionnaires each visit of the outpatient clinic
Two hospitalizations of one day to start the switch to hyqvia (is done in every
patient that begins with IVIg in our department). After that follow up is done
in the outpatient clinic. The relatively high frequency of visits of the
outpatient clinic is not uncommon in MMN patients and therefore not considered
a clear EXTRA burden. It is and will be, however, a burden.
By switching to a subcutaneous infusion pharmacokinetics change and this can
have impact on the functioning of a patient. This will be very detailed
monitored in the successive outpatient visits. If necessary hyqvia dosing can
be raised of a reswitch can be done to IVIg.

Risks:
A possible risk/change compares to the current treatment is the addition of
rHuPH20. There is already a much data of patients with immunodeficiencies that
use hyqvia. No major problems have been seen. Antibodies against rHuPH20 are
seen, no neutralizing anti-rHuPH20 antibodies are detected. Cumulative risks
are estimated low.