Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare the proportion of patients who could withdraw from prednisone and hydrocortisone one year after a progressive decrease of GC (GC tapering) or a hydrocortisone replacement therapy in rheumatoid arthritis in remission or low disease activity.

Detailed Description
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French multicenter double-blind controlled parallel-group randomized clinical trial Phase IV assessing whether a hydrocortisone replacement therapy could increase the success rate of GC withdrawal at one year, in patients with Rheumatoid Arthritis in low disease activity or remission, in comparison to progressive decrease of GC (GC tapering).

Official Title
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Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients in Low Disease Activity or Remission.

Conditions
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RheumatoId Arthritis

Intervention / Treatment
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* Drug: GlucoCorticoid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old. Fulfilling the 2010 American College of Rheumatology (ACR)/EULAR criteria for RA. Treated with a stable dose of Synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) or Biological Disease Modifying Anti-Rheumatic Drug (bDMARD) for at least 3 months. Who have been treated with prednisone or prednisolone for at least 6 months. With a stable dose of prednisone or prednisolone of 5mg/day for at least 3 months. With a DAS28 ≤3.2 for at least 3 months. Patients with health insurance Patients who have signed a written informed consent form. Exclusion Criteria: Any chronic condition that would need long term corticoid use (e.g. chronic lung diseases). Evidence of a flare within the last 3 months. Evidence of an allergy or intolerance to hydrocortisone or prednisone. Chronic idiopathic, or autoimmune clinical adrenal insufficiency. GC joint injections within the last 3 months or scheduled in the next 3 months. Any GC intake expected more than >5mg/day within the next 12 months. Association with sultopride and with live vaccines Significant trauma or major surgery within the 3 months prior to the baseline visit. Scheduled surgery in the next 12 months. Fibromyalgia. Foreseeable poor compliance with the strategy. Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation. Alcohol and/or drug misuse as determined by the investigator. Pregnancy or breastfeeding. Patient is not willing to sign the informed consent. Juridical Protection DAS28>3.2 after one month of a stable dose of prednisone 5 mg/day.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucocorticoid (GC) tapering<br>GC tapering group: patients will be asked to taper prednisone taken every morning at 8.00 AM by decreasing the daily dose by 1 mg every month as soon as they are in remission or Low Disease Activity (LDA). In addition they will receive a placebo of 20 mg/day of hydrocortisone (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg/day (at 8.00 AM) of hydrocortisone placebo for 3 months before discontinuing the hydrocortisone placebo. | Drug: GlucoCorticoid<br>* After inclusion in the study, the first part is an open follow-up period where all patients will receive 5 mg of prednisone daily for one month. After one month, if patients still have a DAS28 ≤3.2, they will be randomized into two arms: Group 1: GC tapering group / Group 2: Hydrocortisone replacement group. After randomisation, there are four scheduled visits: M4, M7, M9 and M12. Patients withdrawing from GC therapy will be instructed, that if they start feeling unwell during or after the GC tapering protocol they should not taper the steroid dose any further, but contact the centre responsible for the protocol. If GC induced adrenal insufficiency is confirmed or strongly suspected, GC replacement will be secured using hydrocortisone.<br>* Other names: Prednisone, Hydrocortisone;|
| Active Comparator: Hydrocortisone replacer<br>Hydrocortisone replacer group: patients will replace prednisone with 20 mg of hydrocortisone on a daily basis (10 mg at 8.00 AM, 10 mg at 12.00 AM) for 3 months then 10 mg daily (at 8.00 AM) for 3 months then stop as soon as they are in remission or LDA, as well as a prednisone placebo (at 8.00 AM) with a schedule to taper the prednisone placebo by 1mg/day every month until discontinuation. | Drug: GlucoCorticoid<br>* After inclusion in the study, the first part is an open follow-up period where all patients will receive 5 mg of prednisone daily for one month. After one month, if patients still have a DAS28 ≤3.2, they will be randomized into two arms: Group 1: GC tapering group / Group 2: Hydrocortisone replacement group. After randomisation, there are four scheduled visits: M4, M7, M9 and M12. Patients withdrawing from GC therapy will be instructed, that if they start feeling unwell during or after the GC tapering protocol they should not taper the steroid dose any further, but contact the centre responsible for the protocol. If GC induced adrenal insufficiency is confirmed or strongly suspected, GC replacement will be secured using hydrocortisone.<br>* Other names: Prednisone, Hydrocortisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients who could withdraw from prednisone and hydrocortisone at one year | To compare a prednisone tapering strategy to a hydrocortisone replacement strategy on the success rate of prednisone and hydrocortisone withdrawal at one year in Rheumatoid Arthritis patients in low disease activity or remission. | one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients who could withdraw from prednisone | To compare the proportion of patients who could withdraw from prednisone whatever the additional hydrocortisone associated treatment. | one year after a progressive decrease of Glucocorticoids or hydrocortisone replacement | 
| proportion of patients with acute adrenal insufficiency | To compare the proportion of patients with acute adrenal insufficiency at one year between the two groups. | one year | 
| proportion of patients with biological adrenal insufficiency | To compare the proportion of patients with biological adrenal insufficiency at one year between the two groups. | one year | 
| proportion of patients needing extra prednisone to control flares | To compare the proportion of patients needing extra prednisone to control flares | one year | 
| proportion of patients who have at least one flare confirmed by the investigator during the protocol. | To compare the proportion of patients who have at least one flare confirmed by the investigator during the protocol. | one year | 
| area under the curve of means of the FLARE (Flare Assessment in Rheumatoid Arthritis) | To compare the area under the curve of the means of the FLARE (Flare Assessment in Rheumatoid Arthritis) at one year with a self-assessment questionnaire. | one year | 
| proportion of patients in DAS28 remission and in DAS28 low disease activity | To compare the proportion of patients in DAS28 remission and in DAS28 low disease activity at 7 and 12 months between the groups. | 7 and 12 months | 
| medians of Health Assessment Questionnaire (HAQ) | To compare the medians of HAQ at 4, 7 months and one year between the groups. | 4, 7 months and 1 year | 
| medians of Rheumatoid Arthritis Impact of Disease (RAID) | To compare the medians of RAID at 4, 7 months and one year between the groups. | 4, 7 months and 1 year | 
| medians of EuroQol 5-dimensional Descriptive system (EQ-5D) | To compare the medians of EQ-5D at 4, 7 months and one year between the groups. | 4, 7 months and 1 year | 
| medians of Functional Assessment of Chronic Illness Therapy - Fatigue Scale FACIT-F) | To compare the medians of FACIT-F at 4, 7 months and one year between the groups. | 4, 7 months and 1 year | 
| proportion of patients with Serious Adverse events | To compare the proportion of patients with Serious Adverse events at one year between the groups. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low disease activity, remission