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ID
Source
Brief title
Health condition
Idiopathic inflammatory myopathy, with the exception of inclusion body myositis.
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in Total Improvement Score (week 12 compared to baseline)
Secondary outcome
Time to improvement (TIS>40 points), mean prednison dosage, health-related quality of life, fatigue, pain, physical activity, IgG blood levels, muscle MRI, cutaneous dermatomyositis disease area and severity, 'samengestelde vragenlijst zorggebruik en productiviteitsverlies'
Background summary
Rationale:
In patients with myositis early immunomodulation by intensive treatment (“hit-early/hit-hard” principle) may induce faster reduction of disease activity and prevent chronic disability by disease damage. Intravenous immunoglobulin (IVIg) in addition to standard treatment with prednisone may be beneficial for this purpose: add-on IVIg improves symptoms in steroid-resistant myositis, and monotherapy IVIg leads to a fast and clinically relevant response in nearly 50% of the patients with myositis who were treatment naive (pilot study in 20 patients).
Objective:
The primary aim is to examine whether early addition of IVIg to standard treatment with prednisone in patients with newly diagnosed myositis leads to superior clinical outcome after 12 weeks.
Our secondary aims are to examine the effect of the intervention on health-related quality of life, physical activity and a biomarker (muscle MRI) on the short and longer term.
Study design:
A double blind controlled randomized clinical trial.
Study population:
Adult patients (≥18 years) diagnosed with idiopathic inflammatory myopathy (except inclusion body myositis) will be invited.
Intervention (if applicable):
Administration of 2 gram/kg IVIg at baseline and after 4 and 8 weeks (intervention arm), or placebo (Saline 0.9%) infusions at baseline and after 4 and 8 weeks (control arm). All patients will be treated with 1 mg/kg prednisone (max. 80 mg daily), which is standard care.
Main study parameters/endpoints:
The Total Improvement Score (TIS) of the myositis response criteria at week 12 (compared to t=0).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Following a screening visit at the outpatient clinic, patients will be admitted to the neurology ward of the Amsterdam UMC for the first day of the study treatment. The remaining study medication will be administered at home, according to routine clinical practice for IVIg treatment in neuromuscular disorders. A second study treatment will be administered at home after 4 and 8 weeks. At baseline and after 4, 8, 12, 26 and 52 weeks outcome assessments will be performed at the outpatient clinic. The outpatient study clinic visits at baseline and after 12, 26 and 52 weeks will be combined with regular outpatient clinic visits. The additional burden related to outcome assessments will consist of MRI muscle imaging after 12 weeks, basic physical examination (manual muscle strength testing), blood sampling after 4 and 8 weeks and filling in questionnaires at baseline and after 4, 8, 12, 26 and 52 weeks. In addition, participants are asked to wear a watch for three episodes of two weeks within the first 12 weeks anf for one week after 26 weeks
Study objective
Early IVIg treatment in addition to prednisone results in a meaningful clinical response in treatment naive myositis patients in the short term and increased HR-QoL in the long term
Study design
Week 0, week 4, week 8, week 12, week 26, week 52
Intervention
Three times 2g/kg IVIg or placebo, at 4-week-intervals, directly following a diagnosis of IIM
Inclusion criteria
• Adult patients (18-80 years) with idiopathic inflammatory myopathy (IIM), according to diagnostic criteria:
- Dermatomyositis
- Non-specific/overlap myositis including antisynthetase syndrome; formerly known as polymyositis
- Immune mediated necrotizing myopathy
• Disease duration < 12 months
• Minimal disability defined as at least 10% loss on Manual Muscle Testing (MMT) and abnormal scores on two other Core Set Measures (CSMs) of the international Myositis Assessment and Clinical Studies (IMACS) group (see ‘Primary and secondary outcomes’).
• Signed informed consent
Exclusion criteria
A potentially eligible patient who meets any of the following criteria will be excluded from participation in this study:
• Disease duration > 12 months
• Immunosuppressive medication or immunomodulatory treatment within the last 3 months (e.g. azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, cyclophosphamide, ciclosporine, IVIg, biologicals, Janus kinase inhibitors, plasmapheresis).
• Severe muscle weakness (i.e. bedridden, severe dysphagia, or respiratory muscle weakness) necessitating more intensive treatment than standard glucocorticoids.
Exceptions to abovementioned exclusion criteria:
Prior use of steroids will be carefully judged by the treating physician. Patients are eligible for inclusion if there is no clinical evident response to prior treatment with:
• High-dosed steroids, such as dexamethasone or intravenous methylprednisolone (e.g. 1000mg daily for three days) within 1 week prior to inclusion.
• Daily dosed prednisone 1mg/kg, or equivalent, used for up to 2 weeks prior to screening visit.
• Treatment with low dose prednisone up to three months before screening.
• Use of biologicals or other immunosuppressive or immunomodulatory treatment when meeting the following criteria:
- Stable dose for the past 6 months
- The biological has been approved for a non-muscular condition (e.g. hematological condition, eczema) and is not known for its use in idiopathic inflammatory myopathy
- No history of biological-induced inflammatory myopathy
• Related to IVIG:
- History of thrombotic episodes within 10 years prior to enrolment
- Known allergic reactions or other severe reactions to any blood-derived product
- Known IgA deficiency and IgA serum antibodies
- Pregnancy (wish)
- Use of loop diuretics
- Use of nephrotoxic medication
• Conditions that are likely to interfere with:
- Compliance (legal incompetent and/or incapacitated patients are excluded), or,
- Evaluation of efficacy (e.g. due to severe pre-existing disability as a result of any other disease than myositis or due to language barrier)
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9722 |
| Other | METC AMC : METC2020_180 |