Immunosuppressant Management for Rheumatic Diseases

Overseen By Lauren Drillock

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Immunosuppressants

Disqualifiers: Active infections, Malignancies, Pregnancy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how varying the duration of stopping immunosuppressants before shoulder replacement surgery affects individuals with rheumatic diseases such as rheumatoid arthritis or lupus. It compares the usual stop period with a shorter one to determine which leads to fewer flares, less pain, and fewer complications. Individuals who have taken immunosuppressants for at least three months and are planning a shoulder replacement may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial involves stopping immunosuppressant medications for a certain period before surgery, but the exact duration is not specified. If you have severe SLE, you will need to stay on your current treatment.

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

Research shows that many drugs used in this trial are generally well-tolerated. For example, studies on Abatacept report a 6.7% complication rate after surgery in patients with rheumatoid arthritis, which is relatively low. Anakinra is also considered well-tolerated, with mostly mild reactions at injection sites.

Adalimumab has mixed safety data. Some studies suggest it may increase the risk of infections after surgery, while others show different results. Belimumab has not shown any new safety concerns over five years of use in certain conditions.

Certolizumab commonly causes side effects like respiratory infections and rashes. Similarly, Cyclosporine is considered safe for patients with rheumatoid arthritis who don't respond to standard treatments.

Hydroxychloroquine is known for its good safety record, with no increased risk of infection. Infliximab, when given within four weeks of surgery, does not show a higher risk of serious infections.

Methotrexate has not been linked to an increase in complications after surgery, and Tocilizumab has a low rate of surgical complications at 8.6%.

Overall, these treatments are generally safe, although some, like Adalimumab and Rituximab, may carry a risk of infection. Always discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores new ways to manage immunosuppressant use in patients undergoing surgery for rheumatic diseases. Unlike the standard protocol, which requires patients to stop their medication for a longer period before surgery, the experimental approach aims to shorten this hold based on each drug's pharmacokinetics. This could potentially minimize the risk of disease flare-ups while still maintaining safety around surgery. If successful, this trial could lead to a more personalized and effective management strategy for patients, reducing complications and improving recovery times.

What evidence suggests that this trial's treatments could be effective for rheumatic diseases?

This trial will compare two different immunosuppressant management protocols for rheumatic diseases. Research has shown that many treatments in this study effectively manage rheumatic diseases. For example, abatacept reduces inflammation and symptoms in people with rheumatoid arthritis over time. Adalimumab has delivered excellent results in treating rheumatoid arthritis, with many patients responding well. Anakinra also reduces symptoms, though some studies suggest it might not be as strong as adalimumab. Azathioprine manages rheumatoid arthritis by calming the immune system. Belimumab has significantly improved patients with systemic lupus erythematosus, a condition related to rheumatic diseases. Overall, strong clinical evidence supports these medications' effectiveness in treating various rheumatic diseases. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Samuels, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for patients with rheumatic diseases like Rheumatoid Arthritis or Lupus, who are planning to undergo elective shoulder replacement surgery. Participants should be on immunosuppressants and willing to adjust their medication timing before surgery.

Inclusion Criteria

Able and willing to provide written informed consent prior to any study specific procedures

I am 18 years old or older.

I have been diagnosed with a rheumatic disease.

Exclusion Criteria

I am unable to give written consent for the study.

I do not have any active infections or other cancers.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Immunosuppressant Hold

Participants follow either a standard or shorter immunosuppressant hold protocol before surgery

Varies based on protocol

Surgery and Immediate Postoperative

Participants undergo shoulder arthroplasty and medications are restarted postoperatively

1-2 weeks

Follow-up

Participants are monitored for safety, effectiveness, and changes in pain and functional outcomes

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Adalimumab
• Anakinra
• Azathioprine
• Belimumab
• Bimekizumab
• Canakinumab
• Certolizumab
• Cyclosporine
• Etanercept
• Golimumab
• Guselkumab
• Hydroxychloroquine
• Infliximab
• Ixekizumab
• Leflunomide
• Methotrexate
• Mycophenolate
• Risankizumab
• Rituximab
• Secukinumab
• Sulfasalazine
• Tacrolimus
• Tocilizumab
• Tofacitinib
• Upadacitinib
• Ustekinumab

Trial Overview

The study aims to compare the effects of stopping immunosuppressant drugs for different lengths of time before shoulder surgery. It will look at flare-ups, pain levels, function outcomes, wound issues, infections, and any return trips to the operating room.

How Is the Trial Designed?

Group I: Shorter hold Experimental Treatment 27 Interventions

Patients will follow an abbreviated immunosuppressant hold protocol, withhold durations modified based on drug pharmacokinetics to allow a shorter preoperative discontinuation period. Medications will be prescribed as usual by the patient's rheumatologist, only adjusting the interval between last preoperative dose and surgery. The rheumatologist will relay the number of weeks/days between the last dose and surgery date. Postoperatively, medications will be restarted approximately 1 week after surgery (+/- 2 days), provided there are no signs of infection or wound healing complications. Route of Administration

Group II: Standard hold Active Control 27 Interventions

Patients will follow the standard perioperative immunosuppressant hold protocol based on guidelines from hip and knee arthroplasty literature. The duration of the hold is determined by medication half-life and infection risk considerations. Postoperatively, medications will be restarted approximately 2 weeks after surgery (+/- 2 days), contingent on wound healing and infection status.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Citations

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Efficacy Data - ORENCIA® (abatacept)

ORENCIA® (abatacept) was studied in clinical studies containing comorbid moderate to severe rheumatoid arthritis patients. Learn more.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3383476/

The Efficacy and Safety of Abatacept in Rheumatoid Arthritis

The most robust data demonstrating increasing clinical and X-ray improvements over time with abatacept treatment come from the 1-year placebo controlled AIM ( ...

3.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(23)02649-1/fulltext

Abatacept in individuals at high risk of rheumatoid arthritis ...

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4.

jrheum.org

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Longterm Safety and Efficacy of Subcutaneous Abatacept ...

These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA.

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0140673623026508

Abatacept inhibits inflammation and onset of rheumatoid ...

6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk.

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academic.oup.com

academic.oup.com/rheumatology/article/56/4/629/2800568

Safety of surgery in patients with rheumatoid arthritis treated ...

The rate of postoperative complications in RA patients treated with abatacept is evaluated at 6.7%. A shorter treatment with abatacept and ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6446585/

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Safety of surgery in patients with rheumatoid arthritis treated by abatacept: data from the French Orencia in Rheumatoid Arthritis Registry. Rheumatology ...

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Safety of surgery in patients with rheumatoid arthritis treated by abatacept: data from the French Orencia in Rheumatoid Arthritis Registry.

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jhandsurg.org

jhandsurg.org/article/S0363-5023(21)00752-8/fulltext

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Safety of surgery in patients with rheumatoid arthritis treated by abatacept: data from the French Orencia in Rheumatoid Arthritis Registry.

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2022 American College of Rheumatology/American ...

Guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee ...