Rituximab Effect on Decreasing glUcoCorticoid Exposition in PolyMyalgia Rheumatica Patients Experiencing a PMR Relapse

Study Overview
=================
Brief Summary
-----------------
Polymyalgia rheumatica (PMR) is prevalent among elderly. Untreated, it leads to major reduction in quality of life. Glucocorticoids are the cornerstone of treatment, but have drawbacks, warranting glucocorticoid sparing treatment. A proof of concept study on Rituximab (RTX) vs placebo showed efficacy in 48 vs 21%(p=0.049) in glucocorticoid free remission after 21 weeks (Marsman et al. 2021). Though promising, the short study duration, small sample size and only few relapsing patients included in this study require further confirmation. Therefore a larger randomised controlled trial with longer follow up will be performed on RTX efficacy on glucocorticoid free remission in relapsing PMR patients during glucocorticoid taper.

Official Title
-----------------
Rituximab Effect on Decreasing glUcoCorticoid Exposition in PolyMyalgia Rheumatica Patients Experiencing a PMR Relapse

Conditions
-----------------
Polymyalgia Rheumatica

Intervention / Treatment
-----------------
* Drug: Rituximab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Polymyalgia rheumatica (PMR) diagnosis fulfilling the 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria Experiencing a PMR relapse, defined as recurring of symptoms and increase in erythrocyte sedimentation rate (ESR)/ C reactive protein (CRP) Unable to reduce glucocorticoid dose below 5mg/day prednisolone or equivalent Informed consent Exclusion Criteria: Treatment with systemic immunosuppressants (other than GC, MTX, leflunomide and azathioprine) 3 months prior to inclusion; (clinical) suspect concomitant giant cell arteritis or other rheumatic inflammatory diseases; concomitant conditions that might significantly interfere with PMR pain or movement evaluation as judged by the investigator; previous hypersensitivity for RTX or contra-indications to RTX.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>1000mg rituximab intravenously once | Drug: Rituximab<br>* 1000mg rituximab in 250ml NaCl 0.9% intravenously<br>* Other names: Truxima;|
| Placebo Comparator: Placebo<br>0mg rituximab (placebo) intravenously once | Drug: Placebo<br>* Placebo in 250ml NaCl 0.9% intravenously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between group difference in percentage of patients in glucocorticoid-free remission | Between group difference in percentage of patients in glucocorticoid-free remission (PMR activity score < 10) at week 52 | At week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients in glucocorticoid-free remission | Percentage of patients in glucocorticoid-free remission | 21 weeks | 
| Percentage of patients with glucocorticoid dose of ≤5mg/day | Percentage of patients with glucocorticoid dose of ≤5mg/day | 52 weeks | 
| Number of relapses | Number of relapses | 52 weeks | 
| Time to glucocorticoid-free remission | Time to glucocorticoid-free remission in days during the study period | 52 weeks | 
| Time to relapse | Time to relapse in days during the study period | 52 weeks | 
| Cumulative glucocorticoid dose | Cumulative glucocorticoid dose | 52 weeks | 
| Percentage of patients needing RTX/Placebo retreatment | Percentage of patients needing RTX/Placebo retreatment | 52 weeks | 
| Adverse events | Adverse events | 52 weeks |