This study is designed as an explorative study aiming at exploring safety and efficacy of immunoadsorption (IA) in patients with Chronic Inflammatory Demyelinating Poly-neuropathy (CIDP) compared to intravenous immunoglobulins (IVIg) and methyl-prednisolone (MP). For this purpose, approximately 140 patients with CIDP will be included within the framework of the German multicenter network "Kompetenznetz Peripherer Nerv" (KKPNS).

The study will be purely observational. IA will be performed as an escalation therapy, i.e., in patients who did not respond to IVIg and/or MP treatment. Patients will be included in the study during ongoing IVIg or MP treatment and switched to IA during the 18-month observation period in case of an insufficient response. IA will be performed according to the therapeutic scheme of each participating center. A non-mandatory recommendation for number of sessions, treatment volumes, and frequency will be given (see below). Six-month follow-up visits including collection of standardized clini-cal data will be performed.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune-inflammatory disease which mainly affects the myelin sheaths of peripheral nerves, leading to paresis and sensory deficits.

Therapy of CIDP includes treatment with IVIg (evidence class Ia), MP (Ib), plasma exchange (PE; Ib), and various immunosuppressive drugs (IV). The European Federation of Neurological Societies (EFNS) guidelines recommend to begin with IVIg or MP as non-invasive options which are easy to apply, and to use PE in case of insufficient therapeutic response.

IA is a highly effective and well tolerated method to remove autoantibodies from the blood. Further proposed mechanisms of action include induction of autoantibody redistribution and subsequent immunomodulatory changes. During the procedure, the patient's plasma runs through adsorber systems which selectively bind human immunoglobulins before it is returned to the patient. Therefore, in contrast to PE, all other plasma proteins like coagulation factors are largely preserved, allowing higher treating frequencies and higher plasma volumes (PVs) to be processed. Adverse events in PE which are based on the loss of plasma proteins (like bleeding complications due to the loss of coagulation factors) are rare in IA, which is generally considered as a low-risk therapy. Furthermore, no substitution solutions like human albumin solutions or fresh frozen plasma are needed. Thus, better tolerability of IA compared to PE is regarded as one of the main advantages of IA and has been demonstrated in clinical studies. However, evidence for efficacy for IA in CIDP is low.

The objective of this trial is to investigate whether IA constitutes an effective and safe escalating therapeutic option in CIDP. For this purpose, IA will be performed in patients who showed insufficient therapeutic response to IVIg and/or MP, or who showed significant side effects under IVIG and/or MP therapy, and progression rates under therapy will be compared before and after the switch to IA.

One previous study in 20 patients8 found a higher response rate for patients treated with IA compared to PE (66.7% vs. 44.4%) after a follow-up of 4 weeks. Another non-randomized trial found that patients with therapy-refractory progressive disease courses could be stabilized by periodical cycles of IA9. However, in summary, evidence for the use of IA in CIDP is low, especially since there are no studies investigating the mid-term and long-term effects of repeated IA compared to other treatment options, and most studies refer to small sample sizes.

Therefore, in this study, we seek to evaluate safety and efficacy of IA in therapy-refractory CIDP in a prospective study design over a prolonged period of time, applying periodical cycles of therapies. Various standardized primary and secondary efficacy endpoints will be collected. The conduction within the German KKPNS network of specialized CIDP centers will facilitate the inclusion of 140 patients, enabling significantly higher evidence levels compared to pre-existing studies.

Objectives:

1. to investigate efficacy of IA measured by CIDP score and various other standardized efficacy parameters compared to a preceding IVIG and/or MP therapy.
2. to investigate safety of IA measured by type and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) compared a preceding IVIG and/or MP therapy.
3. to investigate the effect of IA on various additional secondary endpoints, such as quality of life, compared to a preceding IVIg and/or MP therapy.

Inclusion Criteria:

• Diagnosis of CIDP based on the EAN/PNS Guidelines on Diagnosis and Treatment of CIDP13
• age ≥ 18 years
• Willing and capable of giving written informed consent
• Currently receiving IVIg or MP treatment OR starting IVIg or MP treatment at baseline

Exclusion Criteria:

• none

CIDP patients currently under treatment with immunoglobulins or steroids will be included in the study.