Combined Treatment of Methotrexate + Glucocorticoids Versus Glucocorticoids Alone in Patients With PM and DM
Status:
Completed
Trial end date:
2014-11-01
Target enrollment:
Participant gender:
Summary
Therapeutical trial in patients with idiopathic polymyositis (PM) and dermatomyositis (DM) is
proposed. The study will investigate the safety and efficacy of combined methotrexate (MTX) +
glucocorticoids (GC) treatment compared with GC alone.
This will be a randomised, open-label, assessor-blind, international multicenter trial,
performed in several European centres interested in research on inflammatory myopathies
(IIM).
A total number of 50 patients with PM/DM will be randomised into two groups (1: MTX+ GC and
2: GC only). Patients will be equally distributed between the two groups providing 25
patients per treatment arm. The randomisation will be based on random numbers generated by a
computer program. After being enrolled in the study, the patients will receive 12 months of
therapy followed by a 12-month follow-up period.
The primary endpoint is the total dose of GC ( in mg/kg weight), which will be administered
for 12 months between baseline and the end of treatment.
There are several of secondary objectives, which will be pursued during and after the trial.
Disease activity and damage will be prospectively assessed by tools for myositis disease
activity (MYOACT and MITAX) and for myositis damage (MYODAM and MDI), global assessment of
activity and damage by patients and by physician, muscle endurance, muscle strength by manual
muscle testing, enzyme levels, GC related side effects, functional ability measured by HAQ,
quality of life by SF-36, and number of patients with treatment failures. The other aims will
also include (i) search for reliable prognostic parameters in the further prognosis of
patients with PM/DM and (ii) studies on the pathogenic aspects of IIM. The investigations of
serum, lymphocytes, muscle tissue and MRI will be organized. DNA and RNA will be stored for
future genetic studies.
Patients with definite or probable PM or DM diagnosed according to diagnostic criteria will
be enrolled. They will have disease activity that according to physician's own judgement
requires high dose immunosuppressive treatment (based on clinical assessment of weakness,
elevation of muscle enzymes and, if available, on magnetic resonance imaging findings).
Patients should be previously untreated with the exception of GC treatment up to 8 weeks.
Patients with other than primary idiopathic PM or DM, such as drug-induced myositis, myositis
in association with other connective tissue disease, inclusion body myositis, malignancy
related myositis, and juvenile DM will be excluded.
All patients will start with prednisone 1 mg/kg/day and the dose will be tapered if patients
meet definition of improvement, which has been proposed by IMACS group. MTX will be
administered orally, once weekly, with a starting dose 10 mg. This will be increased
gradually to 25 mg/week if tolerated by week 5. Patients will be first assessed after 2 weeks
and than monthly for a period of 48 weeks. There will be a follow-up after a further 1 year
in order to find out the impact of the early treatment on the long-term disease outcome.
All efficacy analyses will be performed using intention-to-treat population (ITT). In
addition, the primary and secondary variables will be analysed using the per-protocol
population, which will contain all patients in the ITT population, who also reached Week 48
without any major protocol violations. The safety population, which will contain any patient
who received at least one dose of study drug, will be used for all safety analyses.