Dynamic Treatment Regiments for Glucocorticoid Tapering

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to better understand how people with rheumatoid arthritis (RA) respond to gradual dose reduction, or tapering, of steroid medications like prednisone. Some people with RA have symptoms when steroid dose is reduced, while others don't. This trial will look at different patient characteristics, including levels of inflammation in the body, differences in the way the brain processes sensory information, and certain hormone levels, to help researchers better understand why different people have these different responses to steroid tapering. The hypotheses include: Greater or equal to ( ) 30% of participants in each arm will develop taper intolerance (either subjective, objective, or both) during the study period Greater or equal to 60% of participants will reduce Glucocorticoid dose by at least 5 Milligrams per day during the study period

Official Title
-----------------
Using SMART Design to Develop Dynamic Treatment Regimens for Glucocorticoid Tapering

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Oral prednisone Taper
* Drug: 150-day taper prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to read and speak English to allow for written informed consent and patient-reported outcomes measures. Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Ability to take oral medication and be willing to adhere to the study intervention regimen Diagnosis of rheumatoid arthritis by a medical provider, confirmed by checking medical records. Current use of an RA treatment regimen of both oral prednisone and 1 other Food and Drug Administration-approved disease-modifying antirheumatic drug (DMARD), with no change in this therapy over the past 90 days Eligible DMARDs include the following: hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, abatacept, tocilizumab, sarilumab, rituximab, tofacitinib, baricitinib, upadacitinib Patients enrolling in the 15-day taper must be taking 7.5mg/day oral prednisone Patients enrolling in the 150-day taper must be taking 5mg/day oral prednisone Exclusion Criteria: Current or recent (past year) use of systemic glucocorticoid (oral, intravenous, or intramuscular administration) >2 weeks for an indication other than RA, to reduce risk of adverse health outcomes related to worsening of the indicated condition High RA disease activity, defined as a Clinical Disease Activity Index of greater (>) 10, given high likelihood of taper failure in this population due to increased RA activity alone Pre-existing primary or secondary adrenal insufficiency diagnosed by a physician, given high risk of worsening with prednisone taper Treatment with another investigational drug or intervention within 90 days Pregnancy Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Participants will be allocated to the 15-day strategy preferentially until enrollment goals have been met; once completing the 15-day strategy, many participants will also be eligible to complete the 150-day strategy, and may subsequently enroll in it if they wish.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15-day taper prednisone<br>This will be for 30 days. Participants will be allocated to the 15-day strategy preferentially until enrollment goals have been met; once completing the 15-day strategy, many participants will also be eligible to complete the 150-day strategy, and may subsequently enroll in it if they wish. Participants that are not eligible for the 15-day strategy, but are eligible for the 150-day strategy, will be enrolled in the 150-day strategy. | Drug: Oral prednisone Taper<br>* The 15-day taper group will assess the effect of an approximately 50% oral prednisone dose reduction over 15 days, and will be followed for an additional 15 days after the last dose reduction.<br>* Other names: Prednisolone;|
| Experimental: 150-day taper prednisone<br>This will be for 180 days. Participants who are not eligible for the 15-day strategy, but are eligible for the 150-day strategy, will be enrolled in the 150-day strategy. | Drug: 150-day taper prednisone<br>* The 150-day taper group will assess the effect of reducing oral prednisone by 1 milligram (mg) every 30 days over 150 days, and will be followed for an additional 30 days after the last dose reduction.<br>* Other names: 150-day taper prednisolone;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with subjective taper intolerance | Subjective intolerance, the first point when a participant replies elects to stop glucocorticoid taper due to associated symptoms. This will be assessed using a one-question questionnaire with binary yes and no responses. | Day 30 (15-day taper) or day 180 (150-day taper group) | 
| Number of participants with objective taper intolerance | The first point when a participant develops any one of: increased RA activity (clinical disease activity index [CDAI] increase >2); RA flare (CDAI increase > 1 at a time when participant classifies as flaring); Clinical adrenal insufficiency. | Day 30 (15-day taper) or day 180 (150-day taper group) | 
| Net glucocorticoid dose reduction | The difference (in mg/day) between a participant's prednisone dose at enrollment, and either (1) the dose at which participants first develop taper intolerance, or (2) the dose at the end of study involvement, if participants do not develop taper intolerance. | Day 30 (15-day taper) or day 180 (150-day taper group) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Disease-modifying anti-rheumatic drug, Oral prednisone, Dose reduction, Tapering