do igg level variations in cidp and mmn patients following initial intravenous ivig treatment correlate with ultimate dosing

Conditions: Multifocal Motor Neuropathy (MMN); Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Summary: cidp and mmn are part of a group of chronic inflammatory conditions that affect the peripheral nervous system. in cidp, there is chronic inflammation of the peripheral nerves and nerve roots leading to demyelination. the myelin sheath is vital in the rapid propagation of nerve impulses between the central nervous system and the peripheral sensory receptors and muscles. by definition cidp must progress over 8 or more weeks and can either have a slowly progressive disease course or a relapsing course with periods of improvement. patients typically present with a non-length dependent neuropathy that affects motor (i.e. weakness of proximal or distal muscles, fatigue, swallowing difficulty, double vision, breathing difficulties etc) and sensory function. mmn is a similar condition to cidp. it is an autoimmune demyelinating neuropathy that leads to slowly progressive asymmetrical weakness that worsens over years without treatment. ivig is a recognised treatment for cidp and mmn. a standard starting dose of 2 g/kg/course, spread over 2-5 days, has been widely used in both research and clinical practice. due to the chronic nature of cidp and mmn, most patients with these conditions require repeated doses to avoid relapse, but the frequency of courses and the total dose of ivig per course required to achieve a steady state varies between patients. given the modest risks involved with ivig and its cost, the lowest possible dose and frequency of administration are preferred. current strategies to reduce dose and frequency involve assessing clinical response to lower doses, but this is both time consuming and imprecise.

the study is designed to slot into normal clinical care, with some extra blood tests performed at times patients would already be attending hospital. an extra blood test is desired 1 week following initial ivig treatment which would require an extra visit, but this is an optional part of the study. 1. identification of suitable participant: patient with cidp or mmn for whom treatment with ivig has been decided upon by their treating neurologist. 2. provision of information leaflet and taking of consent. blood test for immunoglobulins (igs), fbc, u\&e, lft and esr will be taken before initial treatment with 2 g/kg ivig; this is all part of usual care. 3. 5-30 min following final infusion of first course of ivig, a blood test for igs, fbc, u\&e, lft and esr will be taken. 4. if the patient is willing to make an extra visit 7 days after day 1 of ivig treatment, they will attend for further igs, fbc, u\&e, lft and esr. 5. when the patient attends at 2 weeks for post-ivig assessment as part of usual care, a blood test for igs, fbc, u\&e, lft and esr will be measured again. 6. usual process of ivig treatment optimisation will then occur (as practised at the walton centre). this is part of usual care, with determination of ivig dosing interval following clinical optimisation by dose suspension, followed by restabilisation and subsequent dose reductions to determine minimum effective dose. 7. at the 3rd consecutive infusion of ivig at the minimum effective dose, a pre-ivig (trough) level of igs will be taken for the minimum effective igg level alongside fbc, u\&e, lft and esr. 8. statistical analysis looking for correlations between the initial ∆igg values and the final dose and dosing interval of ivig will be undertaken.

Eligibility criteria:
inclusion criteria: * adult patients with cidp or mmn who are starting intravenous immunoglobulin in the walton centre * informed consent exclusion criteria: * previous intravenous immunoglobulin use in the last year * age under 18 * lack of mental capacity to consent to treatment or to study participation * concurrent treatment with steroids or other immunosuppressants

Keywords: cidp, igg, immunoglobulin, ivig, transfusion reaction