IgM (anti-MAG) peripheral Neuropathy: from proper assessments to trial needs (IMAGiNe study).

IgM monoclonal gammopathy associated polyneuropathy (MGUSP) is slowly
progressive with differential effects in individuals ranging from mild foot
numbness and minor imbalance to severe neuropathic pain and sensory and motor
dysfunction. Since all trials performed in monoclonal gammopathy of
undetermined significance (MGUS) associated polyneuropathy had negative
results, many questions need to be resolved before attempting other treatments.
Suggested potential factors contributing to the negative results are: repeated
use of suboptimal outcome measures, small trial sizes and low numbers of
treated patients, the indolent disease course needing a longer follow-up period
to capture relevant changes, or the possibility that administered treatments
were not aggressive enough. So far there is no international consensus
regarding how to assess and treat patients with IgM monoclonal gammopathy
polyneuropathy. The IMAGiNe study will result in a unique collection of
prospectively collected and highly standardized clinical data and a biobank
from a large population of well-defined patients with IgM monoclonal gammopathy
associated polyneuropathy. This data will be used to optimize the diagnostic
criteria for possible subtypes, to identify biomarkers to monitor and predict
disease activity and response to treatment, and to predict models for treatment
response and outcome in individual patients.

The main objective is to describe in detail the variation in clinical subtypes,
clinical course, past and current practice of treatment, antibody titers, and
clinical picture of IgM monoclonal gammopathy associated polyneuropathy at the
various levels of assessing outcome. The study group aims to define the
clinical and biological determinants and predictors of this variation in
subtypes, disease activity, treatment response and outcome. In achieving this a
MGUS-specific Rasch-built overall disability scale (MGUS-RODS) will be
constructed from obtained observational data that should fulfill all modern
clinimetric requirements, including cross-cultural validity.

International, multi-center, prospective observational cohort study with a
duration of 3 years (assessments at 0/6/12/24/36 months, plus visits in case
the patient makes extra hospital visits during the study period). The
coordinating centers will be the Maastricht University Medical Center and
University Medical Center Utrecht, both in the Netherlands.

At study entry data will be collected regarding: (1) key clinical features and
results from routine diagnostic work-up, (2) patient history, demography and
current clinical situation defined by patients* complaints, neurological
deficits and various outcome measures, (3) past treatments and treatment at
study entry as well as the clinical response to those treatments, (4) bone
marrow biopsy collected at diagnosis, if available. During the study patients
will visit a total of five times. Four of these visits will be combined with
the regular yearly appointment (t=0, t=12, t=24, t=36 months). During these
regular yearly appointments patients undergo blood tests. During three of
these vena punctures (t=0, t=12 and t=36 months) extra blood will be obtained
for storage in a biobank. During all six visits physical examination will be
performed including determining the (RT)-MRC sum score and (RT)-Modified ISS,
and patients fill in the MGUS-RODS.