Methotrexate as Remission Maintenance Therapy After Remission-Induction With Tocilizumab and Glucocorticoids in Giant Cell Arteritis
- Conditions
- Interventions
- Registration Number
- NCT05623592
- Lead Sponsor
- University of Bonn
- Brief Summary
The standard treatment for Giant Cell arteritis (GCA) is Glucocorticoids(GC), even if GC-related adverse events are commonly occuring. Therefore, other practises for reducing relapses and cumulative GC-doses are needed. Currently, the Interleukin-6-inhibitor tocilizumab is used in combination with GC to achieve higher remission rates and lower cumulative GC-...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 52
- Subjects male or female, aged ≥18 years
- Written informed consent of the capable subject for voluntary participation in the study.
- Diagnosis of GCA as confirmed by the investigator fulfilment (also in retrospect) of the proposed extended 1990 classification criteria for GCA .
- Previous treatment with glucocorticoids and tocilizumab for new or relapsing GCA
- GCA patients who have been treated with tocilizumab and in whom discontinuation of tocilizumab therapy has been decided by the treating rheumatologist, within standard treatment at the department of rheumatology are eligible.
- total tocilizumab therapy should have been at least 6 months before inclusion.
- Patients should be in stable remission (defined as the absence of signs or symptoms of GCA and normal C-Reactive Protein (<1mg/dl), off glucocorticoids for at least 1 months at screening.
- Willing and able to inject methotrexate or placebo subcutaneously at randomization
- Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)
- Severe renal (glomerular filtration rate <30/min) failure
- Conditions other than GCA requiring continuous or intermittent treatment with oral or parenteral Glucocorticoids unless the last exposure to Glucocorticoids was >1 months before screening
- Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
- Current treatment with any other conventional, biologic or targeted synthetic DMARD except tocilizumab
- Elevation of transaminases above three times the norm
- Simultaneous participation in another clinical trial, or participation in a clinical trial taking an investigational product, up to 30 days prior to participation in this clinical trial.
- Pregnant or breast feeding women
- Contraindications for therapy with Methotrexate, as indicated in the summary of product characteristics
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Methotrexate Methotrexate The patient will be treated for 12 months weekly with methotrexate. Methotrexate will be provided at a dose of 17.5mg as a pre-filled syringe for self-injection. A dose reduction to 15 mg/week in case of intolerance, elevated liver enzymes \>3x upper limit of normal or to 10 mg/week if glomerular filtration rate \<50/min will be possible. If glomerular filtration rate \<30/min, termination of treatment. Placebo Sodium chloride Patients receive sodium chloride as a placebo subcutaneously. It will be administered in the form of a pre-filled syringe for self-injection once a week for 12 months.
- Primary Outcome Measures
Name Time Method Time to relapse during the 12 months treatment period 12 months
- Secondary Outcome Measures
Name Time Method Cumulative prednisone doses at months 6, 12 and 18 18 months Self-reported fatigue : FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue Scale) 18 months The possible score ranges from 0 to 52 points. The higher this value, the better the quality of life.
Number of relapses per patient during the 12 months treatment period 12 months Time to first, second and third relapse after randomization 18 months Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab 18 months Health-related quality of life: Short Form-36 18 months The possible score ranges from 0 to 100 points, where 0 points represent the greatest possible health limitation, while 100 points represent no health limitation at all
Patient Global Assessment of disease activity (PGA) 18 months The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.
Investigator reported Evaluator Global Assessment of disease activity (EGA) 18 months The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.
Prevalence of aortitis at baseline and month 12 and 18 in MRI 18 months Patient Assessment of pain 18 months The possible score ranges from 0 to 100 points, where 0 points represent the least pain intensity and 100 the most pain intensity
Occurrence of symptoms and signs related to Giant cell arteritis 18 months Occurrence of adverse events and serious adverse events 12 months Number of vasculitic vessels and change of intima-media-values of temporal and axillary arteries 18 months Proportion of subjects with increased Erythrocyte Sedimentation Rate (>20mm/h) and C-Reactive Protein levels (> 10mg/L) 18 months
Trial Locations
- Locations (1)
Medical Clinic and Polyclinic III Internal medicine Oncology, Hematology University Hospital Bonn, Rheumatology and Clinical Immunology
🇩🇪Bonn, Germany