Intravenous versus Subcutaneous Immunoglobuline therapy in Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare immune mediated disorder
characterized by slowly progressive, asymmetric, predominantly distal weakness
of one or more limbs without sensory loss. Intravenous immunoglobuline IVIg is
considered to be the first line treatment when disability is sufficiently
severe to warrant treatment. Subcutaneous administration of immunoglobuline
(SCIg) seems to be a good alternative route. SCIg is often administered in
patients with immuno-deficiency syndromes with low or absent antibody
production.
Several advantages of SCIg have been reported.
Firstly, weekly SCIg administration produces a stable day-by-day concentration
of IgG. Based on the hypothesis that in MMN patients there is an ongoing
immunological process, a stable concentration would be preferable above
alternating peak and trough levels.
Secondly, SCIg avoids unphysiologically high serum IgG peak levels as produced
by IVIg which are thought to be responsible for some adverse effects.
Thirdly, as SCIg can be administered by the patients themselves, the switch to
SCIg improves health-dependent quality of life and treatment satisfaction.
Finally, SCIg is less expensive.

1. Primary objective:

To evaluate whether subcutaneous immunoglobulin infusion is as effective as
intravenous immunoglobulin in maintaining muscle strength in patients with
multifocal motor neuropathy.

2. Secondary objective:

a) To evaluate whether SCIg is as effective as IVIg in maintaining grip
strength.
b) To evaluate whether SCIg is as effective as IVIg in maintaining functional
status.
c) To evaluate whether SCIg results in a higher level of perceived quality of
life.
d) Assessment of the potential (serious) adverse events, adverse reactions and
suspected unexpected adverse reactions of SCIg, especially local tissue
reaction.
e) To evaluate whether SCIg results in more stable and higher mean IgG serum
levels compared to IVIg.

A single-centre open-label pilot intervention study

After informed consent and baseline assessments, all patients will receive
subcutaneous immunoglobuline (SCIg, Gammaquin) one week after the second IVIg
treatment. Patients shall be instructed how to adminster the SCIg treatments
themselves. SCIg will be administered once a week.
Gammaquin consists of a protein-fraction extracted from normal, human plasma
from at least 1000 donors. Gammaquin contains 160mg/ml protein of which at
least 90% is immunoglobuline G (IgG).
For each patient the monthly IVIg dosis will be assessed at baseline. The
weekly SCIg dosis will be calculated for each individual patient, so that
approximately half of the IVIg dosis that a patient normally receives is given
subcutaneously. If a patient deteriorates on the starting dose, the dose will
be doubled the next week.

The next items will be assessed:
- Weight: first visit
- Two disability checklists: first 2 visits, 3 month, end of study
- Two quality of life questionnaire: first 2 visits, 3 month, end of study
- Adverse events questionnaire: all 11 visits
- Assessment of muscle strength, grip strength and hand function tests: all 11
visits
- Blood samples by finger-prick: all 11 visits (13 times)

The finger-prick is an easy and the least invasive method to determine serum
immunoglobuline concetration.

Local adverse events (redness, itch and pain) are often reported with SCIg.
These reactions were transient and most patients did not perceive them as
troublesome. One of the objectives of this study is to assess the frequency and
intensity of these adverse events.