Prednisone Taper for Rheumatoid Arthritis

(SMART-RA Trial)

Recruiting at 1 trial location

Overseen By Beth Wallace, MD MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Prednisone, DMARDs

Disqualifiers: Pregnancy, Schizophrenia, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how people with rheumatoid arthritis (RA) respond to gradually reducing their dose of prednisone, a common steroid medication. Some experience symptoms when the dose decreases, while others do not, and researchers seek to understand why. Participants will follow one of two tapering plans over either 15 or 150 days. Eligible individuals should have RA, be taking prednisone along with another RA medication, and have maintained the same treatment plan for the last 90 days. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you continue using your current RA treatment regimen, including prednisone and another approved medication, without changes for at least 90 days before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking prednisone at lower doses is generally safe for most people. Studies have found that doses up to 10 mg per day are usually well-tolerated and carry a low risk of serious side effects. Many individuals with rheumatoid arthritis use prednisone to manage inflammation and pain without major issues.

However, prednisone is a steroid and can still cause side effects, such as weight gain, mood changes, or trouble sleeping, especially with long-term use.

This trial examines how patients react when their dose is gradually reduced. The goal is to identify who might experience symptoms during tapering. While the treatment is generally safe, individual responses vary. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the prednisone taper strategies for rheumatoid arthritis because they offer a fresh approach to managing the condition. Unlike current treatments that might require long-term medication use, the 15-day taper prednisone strategy could provide quick relief over a short period, potentially reducing the risk of long-term side effects. Additionally, the 150-day taper strategy offers a more gradual reduction in medication, which might be beneficial for those who need a longer adjustment period to manage symptoms effectively. These strategies aim to provide flexibility and personalization in treatment plans, which is a significant step forward in rheumatoid arthritis care.

What evidence suggests that this trial's treatments could be effective for rheumatoid arthritis?

This trial will compare two prednisone taper strategies for rheumatoid arthritis. Research has shown that prednisone, a type of steroid, can effectively reduce pain in people with rheumatoid arthritis (RA), especially soon after starting treatment. One study found that gradually lowering the prednisone dose from 1 to 4 mg per day, by reducing it by 1 mg every 4 weeks, can help manage symptoms without much discomfort. However, its pain-relieving effects might not be as strong after three months. More than 60% of patients in these studies have successfully reduced their dose by at least 5 mg per day without major issues. This suggests that many people might handle a gradual dose reduction well, though some may feel worse when the dose is lowered, a situation known as taper intolerance. ^{6 7 8 9 10}

Who Is on the Research Team?

Beth Wallace, MD MSc

Principal Investigator

VA Ann Arbor Healthcare System, Ann Arbor, MI

Are You a Good Fit for This Trial?

This trial is for adults with rheumatoid arthritis who are currently on a stable RA treatment regimen including oral prednisone and another approved DMARD, without changes in the last 90 days. They must be able to take oral medication, read and speak English, provide consent, and commit to the study duration. Pregnant individuals or those with high RA activity or recent other steroid use are excluded.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

I can take pills and will follow the study's treatment plan.

I have been diagnosed with rheumatoid arthritis by a doctor.

Exclusion Criteria

Treatment with another investigational drug or intervention within 90 days

Pregnancy

I have been diagnosed with adrenal insufficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

15-day Taper Treatment

Participants undergo a 15-day tapering strategy for prednisone over 30 days

4 weeks

Remote participation or clinic visits as needed

150-day Taper Treatment

Participants undergo a 150-day tapering strategy for prednisone over 180 days

26 weeks

Remote participation or clinic visits as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral prednisone

Trial Overview The trial is testing how reducing doses of prednisone over either 15 days or 150 days affects people with rheumatoid arthritis. It aims to understand why some patients experience symptoms when their steroid dose is lowered by examining inflammation levels, sensory processing in the brain, and hormone levels.

How Is the Trial Designed?

Group I: 150-day taper prednisone Experimental Treatment 1 Intervention

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.

Group II: 15-day taper prednisone Experimental Treatment 1 Intervention

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.

Oral prednisone is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Deltasone for:

• Rheumatoid arthritis
• Lupus
• Vasculitis
• Osteoarthritis
• Psoriatic arthritis

Approved in European Union as Prednisone for:

• Rheumatoid arthritis
• Lupus
• Vasculitis
• Osteoarthritis
• Psoriatic arthritis

Approved in Canada as Prednisone for:

• Rheumatoid arthritis
• Lupus
• Vasculitis
• Osteoarthritis
• Psoriatic arthritis

Approved in Japan as Prednisone for:

• Rheumatoid arthritis
• Lupus
• Vasculitis
• Osteoarthritis
• Psoriatic arthritis

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

Glucocorticoids are effective in managing rheumatoid arthritis due to their strong anti-inflammatory and immunomodulatory properties, but concerns about potential adverse effects limit their use, especially at higher doses and longer durations.

Current evidence on the safety of low-dose glucocorticoid therapy in rheumatoid arthritis is limited, highlighting the need for more quality studies, while new formulations like modified-release prednisone are being developed to enhance their therapeutic benefits and reduce risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid arthritis. Santiago, T., Jacobs, JW., Saag, KG., et al.[2017]

In a real-world study of 95 patients with rheumatoid arthritis using biologic therapies, 54% successfully tapered their glucocorticoid use, and 33% completely discontinued prednisone within 6 months.

Factors such as positive rheumatoid factor, higher inflammation markers, and a shorter time to achieve low disease activity were linked to a higher likelihood of successful glucocorticoid tapering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lowering Expectations: Glucocorticoid Tapering Among Veterans With Rheumatoid Arthritis Achieving Low Disease Activity on Stable Biologic Therapy. Wallace, BI., England, BR., Baker, JF., et al.[2023]

A systematic review and meta-analysis of 13 controlled trials involving 2280 patient-years found no significant increase in the risk of serious infections or severe adverse events (SAEs) when tapering targeted therapies (bDMARDs or JAK inhibitors) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity.

The study indicated that tapering these therapies did not lead to a higher risk of malignancies, cardiovascular adverse events, or deaths compared to continuing the usual care, suggesting that tapering may be a safe option for patients in stable conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis. Vinson, D., Molet-Benhamou, L., Degboé, Y., et al.[2023]

Oral prednisone significantly reduces disease activity in 60% of patients with rheumatoid arthritis (RA) within the first 12 weeks of treatment, based on a study of 40 patients over 18 weeks.

However, after tapering the dose, 58% of responders experienced a rebound deterioration in their condition, suggesting that this tapering strategy may not be advisable for bridge therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. van Gestel, AM., Laan, RF., Haagsma, CJ., et al.[2019]

In a study of 332 rheumatoid arthritis patients, 42.1% were able to successfully taper their biological disease-modifying antirheumatic drugs (bDMARDs) after achieving low disease activity or remission, indicating that dose reduction is feasible in daily practice.

Patients who tapered their bDMARDs were more likely to be on a combination therapy with methotrexate, and the most commonly tapered medications were adalimumab, etanercept, and rituximab, which also led to significant cost savings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapering of biological antirheumatic drugs in rheumatoid arthritis patients is achievable and cost-effective in daily clinical practice: data from the Brussels UCLouvain RA Cohort. Dierckx, S., Sokolova, T., Lauwerys, BR., et al.[2021]

The review emphasizes the importance of tapering biologic therapies in rheumatoid arthritis (RA) after achieving remission, as current guidelines suggest, to reduce adverse effects and costs associated with long-term immunosuppressive therapy.

It provides practical recommendations based on recent clinical trials, focusing on outcomes like flare rates and disease control, and suggests using musculoskeletal ultrasound to identify patients who may successfully taper their biologic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapering biologics in rheumatoid arthritis: a pragmatic approach for clinical practice. Lenert, A., Lenert, P.[2018]

In a study of 36 rheumatoid arthritis patients over 2 years, the use of oral glucocorticoids (GC) was successfully reduced from 100% to 13.9% without worsening disease status, indicating a safe tapering strategy.

The Clinical Disease Activity Index remission rate improved from 25.0% to 38.9%, suggesting that patients maintained or even enhanced disease control while reducing GC use, with only two serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapering and discontinuation of oral glucocorticoids without deterioration of disease status in patients with rheumatoid arthritis under a stable treatment. Hirata, S., Kohno, H., Watanabe, H., et al.[2022]

In a study of 1009 patients with rheumatoid arthritis (RA) receiving intravenous abatacept, 72.7% were prescribed glucocorticoids at the start, with a median dose of 7.5 mg/day.

After 24 months on abatacept, 40.7% of patients were able to reduce their glucocorticoid dose, indicating that abatacept may help in tapering glucocorticoid therapy safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthritis who initiated intravenous abatacept: results from the 2-year ACTION study. Alten, R., Nüßlein, H., Galeazzi, M., et al.[2018]

In the SEMIRA trial involving 259 patients with rheumatoid arthritis, continuing low-dose glucocorticoids (5 mg/day) for 24 weeks resulted in better disease control compared to tapering the dose, with a significant difference in disease activity scores (DAS28-ESR) favoring the continued treatment group.

Despite the benefits of continuing glucocorticoids, about two-thirds of patients were able to taper their glucocorticoid dose safely, indicating that tapering may be feasible for some patients without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Burmester, GR., Buttgereit, F., Bernasconi, C., et al.[2020]

In a study of 508 rheumatoid arthritis patients, tapering glucocorticoids to doses of 0-2.5 mg/day significantly increased the risk of disease flare-ups, with adjusted odds ratios of 1.45 and 1.37, respectively.

Tapering glucocorticoids to doses greater than 2.5 mg/day did not show a significant increase in flare risk, suggesting that maintaining a dose above this threshold may be safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs). Adami, G., Fassio, A., Rossini, M., et al.[2023]

In a study of 437 rheumatoid arthritis patients over 2.5 years, individual tapering of DMARDs did not significantly increase the risk of disease flare-ups or loss of remission compared to those who continued their full dosage.

Patients who tapered their medication experienced a significant reduction in drug costs (by 1017€), while those who did not taper saw an increase in costs (by 1151€), suggesting that tapering can be both safe and economically beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting. Birkner, B., Rech, J., Edelmann, E., et al.[2023]

Citations

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a randomised, placebo-controlled, double-blind trial 20 A third trial showed that a slow tapering of prednisone from 1 to 4 mg/day, with a 1 mg reduction every 4 weeks before discontinuation, ...

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Prednisone Taper for Rheumatoid Arthritis (SMART-RA Trial) Trial Overview The trial is testing how reducing doses of prednisone over either 15 days or 150 days affects people with rheumatoid arthritis. It aims to ...

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The Glucocorticoid Taper: A Primer for the Clinicians - PMC A patient may be continued on once-daily oral prednisolone 5 mg/day administered in the morning, which is further tapered to 2.5 mg/day over 2-4 weeks.

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We Still Don't Know How to Taper Glucocorticoids in ... Initial daily oral GC dose, mg, Prednisolone 60, Prednisolone 5–7.5 ; Taper protocol, Weeks 1–6: weekly decrease by 20–38% of daily dose. Weeks 7 ...

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Prednisone - StatPearls - NCBI Bookshelf - NIH However, when administered at lower doses (≤10 mg/kg daily), they are generally considered safe and are associated with minimal risk of adverse ...

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A Safety Analysis of Oral Prednisone as a Pre-Treatment ... This study will be an open-label prospective analysis of oral prednisone (compared to IV methylprednisolone) as a pre-treatment for rituximab in patients ...

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Effectiveness and safety of oral corticosteroids in the ... Conclusion: Prednisone 5mg and 10mg and prednisolone 5mg and 7.5mg seems to be effective, while prednisone appears to be safer anti-inflammatory ...