Upadacitinib for Blepharitis

Overseen By Dermatology CTU

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: Topical medications

Disqualifiers: Heart disease, Stroke, Neurological, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to assess the efficacy of upadacitinib in eyelid dermatitis that has not resolved with topical therapies and patch testing.

Will I have to stop taking my current medications?

The trial requires that you stop using any topical medications for eyelid dermatitis at least one week before starting the study drug.

What data supports the effectiveness of the drug Upadacitinib for treating blepharitis?

Upadacitinib has shown effectiveness in treating conditions like rheumatoid arthritis and psoriatic arthritis by improving patient outcomes and achieving significant response rates compared to a placebo. Although there is no direct evidence for blepharitis, its success in similar inflammatory conditions suggests potential benefits. ^{1 2 3 4 5}

Is upadacitinib generally safe for humans?

Upadacitinib has been studied for various conditions like rheumatoid arthritis and atopic dermatitis, showing a good safety profile overall. However, it may increase the risk of shingles (herpes zoster) and should not be used with certain medications or in people with active infections or severe liver problems. ^{2 6 7 8 9}

How is the drug Upadacitinib unique for treating blepharitis?

Upadacitinib is unique because it is an oral medication that selectively inhibits Janus kinase 1 (JAK-1), a protein involved in inflammation, and is being explored for various inflammatory conditions, unlike typical treatments for blepharitis which may not target this specific pathway. ^{2 10 11 12 13}

Research Team

Walter Liszewski

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for individuals with persistent eyelid dermatitis, which hasn't improved after using topical treatments and undergoing patch testing. Specific eligibility details are not provided.

Inclusion Criteria

Willing and able participants that comply with study activities

I have tried at least one prescription cream for my eyelid dermatitis without success.

I agree to use birth control during and for 4 weeks after my treatment ends.

Exclusion Criteria

Self-reported history of allergic response to upadacitinib

I am not pregnant, nursing, or planning to become pregnant during the study.

I am using topical medications for eyelid dermatitis and started within the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive upadacitinib 15mg daily for eyelid dermatitis

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Upadacitinib

Trial Overview The study is evaluating the effectiveness of a medication called Upadacitinib at a dose of 15 MG in treating refractory eyelid dermatitis.

Participant Groups

Group I: Upadacitinib Treatment Experimental Treatment 1 Intervention

Participants on upadacitinib 15mg daily

Upadacitinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

Upadacitinib, an oral JAK-1 inhibitor, received marketing approval in the USA in August 2019 for treating moderately to severely active rheumatoid arthritis after showing positive results in multinational phase III trials.

The approval was specifically for patients who had an inadequate response or intolerance to methotrexate, highlighting its role as an effective alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib: First Approval. Duggan, S., Keam, SJ.[2020]

Upadacitinib significantly improves rheumatoid arthritis symptoms, with a 3.71 times higher likelihood of achieving a 20% improvement in the ACR20 score compared to placebo, based on data from 3233 patients.

While upadacitinib is effective, it is associated with a higher incidence of adverse events and infections compared to placebo, particularly at the 12 mg twice daily dosage, although the 15 mg once daily dose combined with Methotrexate showed the best efficacy without significant treatment-related risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Meta-Analysis Evaluating the Effectiveness and Safety of Upadacitinib in Treating Rheumatoid Arthritis in Patients With Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs. Panchal, V., Vyas, BH., Sivasubramanian, BP., et al.[2023]

In a study involving 661 patients with rheumatoid arthritis (RA) who did not respond adequately to conventional DMARDs, upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes such as pain, physical function, and overall disease activity after 12 weeks compared to placebo.

Patients taking upadacitinib reported clinically meaningful improvements in various measures, with the number needed to treat (NNT) for these benefits ranging from 4 to 8, indicating that a small number of patients need to be treated for one to experience significant improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. Strand, V., Pope, J., Tundia, N., et al.[2021]

In a phase 3 trial involving patients with psoriatic arthritis who did not respond to previous treatments, upadacitinib showed significant improvements in patient-reported outcomes (PROs) compared to placebo and was as effective as adalimumab, particularly in measures like the Health Assessment Questionnaire Disability Index (HAQ-DI) and the SF-36 Physical Component Summary score.

Patients treated with upadacitinib experienced rapid improvements in symptoms as early as week 2, with sustained benefits observed through week 56, indicating its efficacy in enhancing quality of life for those with psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1. Strand, V., Mease, PJ., Soriano, ER., et al.[2022]

A total of 4,494 adverse event reports associated with upadacitinib were identified from over 3.8 million reports in the FDA database, indicating a significant number of potential safety concerns.

The study revealed unexpected adverse events such as arthralgia, musculoskeletal stiffness, diverticulitis, and cataracts, with most adverse events occurring within the first four months of treatment, highlighting the need for careful clinical monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system. Wu, XP., Lu, XK., Wang, ZT., et al.[2023]

Upadacitinib has been evaluated for long-term safety in 6991 patients across various conditions, showing that it is generally well tolerated with similar rates of treatment-emergent adverse events (TEAEs) across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis.

While the overall safety profile is favorable, certain risks such as herpes zoster and non-melanoma skin cancer were higher in patients with rheumatoid arthritis and psoriatic arthritis compared to active comparators, indicating the need for careful monitoring in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. Burmester, GR., Cohen, SB., Winthrop, KL., et al.[2023]

Upadacitinib, a selective JAK1 inhibitor, demonstrated an oral bioavailability of approximately 80% for its extended-release formulation compared to the immediate-release version, based on a pharmacokinetic analysis of 11,658 plasma concentrations from 1,145 subjects across multiple studies.

The study found that while certain factors like sex and renal function can affect drug levels in the body, these variations are not expected to lead to clinically significant changes in the drug's effectiveness or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. Nader, A., Stodtmann, S., Friedel, A., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Effects of Upadacitinib on Experimental Autoimmune Uveitis: Insights From Single-Cell Analysis. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Upadacitinib: First Approval. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

A Meta-Analysis Evaluating the Effectiveness and Safety of Upadacitinib in Treating Rheumatoid Arthritis in Patients With Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system. [2023]

7. Spain pubmed.ncbi.nlm.nih.gov

Upadacitinib tartrate in rheumatoid arthritis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib: Mechanism of action, clinical and translational science. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib. [2021]

13. New Zealand pubmed.ncbi.nlm.nih.gov

The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. [2022]