IMMEDIATE study

Rationale:

Idiopathic inflammatory myopathies, inclusion body myositis excluded, are a group of treatable auto-immune disorders. Due to insufficient efficacy or side-effects of corticosteroids, additional immunosuppressive treatment is often needed. Clinical outcome is often disappointing, with many patients having a polyphasic and chronic clinical course. Relative under treatment in the first period resulting in irreversible damage, is thought to contribute to this. While not yet investigated, there are suggestions that early treatment with intravenous immunoglobulins might induce a fast response. We hypothesize that the use of early IVIg leads to fast improvement in newly diagnosed patients.



Objective:

Explore efficacy, safety and feasibility (with respect to a future trial) of early treatment with intravenous immunoglobulins for patients with idiopathic inflammatory myopathies.



Study design:

Investigator initiated, multicenter pilot study with an uncontrolled pre/posttest design.



Study population:

Twenty newly-diagnosed, treatment-naïve adult patients with idiopathic inflammatory myopathies (except inclusion body myositis).



Intervention:

Patients will be given a starting dose of intravenous immunoglobulins 2 gr/kg in 2-4 days and three maintenance treatments of 1 gr/kg thereafter every three weeks.



Main study parameters/endpoints:

The number of patients with clinical significant improvement, defined as ≥40% improvement on a continuous, weighted score of 6 core set measures (as developed by the International Myositis Assessment and Clinical Studies group) after 9 weeks of treatment.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Structured risk analysis shows a moderate risk for patients.



Possible risks

• Side effects: treatment with intravenous immunoglobulins may lead to mild infusion reactions and rarely to serious adverse events such as thrombo-embolic events or hemolysis.

• Possible, temporary undertreatment: the uncertainty regarding efficacy of intravenous immunoglobulins may cause undertreatment in the first 9 week. However, we consider this temporary and adequately manageable with escape medication (consisting of standard corticosteroid therapy).

• Additional study related procedures: follow-up ancillary investigations (MRI, ultrasound, and laboratory investigations) and clinical visits for infusion of intravenous immunoglobulin are considered a minor inconvenience to study participants.



Possible benefits

• Beneficial side effect profile compared to standard treatment with corticosteroids.

• Faster and greater total clinical improvement compared to standard treatment with corticosteroids.

intravenous immunoglobulins will induce a fast and effective response in patients with newly diagnosed idiopathic inflammatory myopathies. Also, the treatment will be generally safe. Furthermore, this pilot study will show feasibility with respect to a future phase 3 study.

primary: after 9 weeks treatment

secondary

- efficacy: after 9 weeks treatment

- safety: during the total duration of the study

- feasibility: end of the study

Study subjects will be treated with intravenous immunoglobulin (Privigen®). Initial dose of IVIg is 2 g/kg over 2-4 days, followed by 3 infusions of 1 g/kg on 1-2 days every 3 weeks