Baricitinib for Pyoderma Gangrenosum

Overseen by Alex G Ortega-Loayza, MD, MCR

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Oregon Health and Science University

Must be taking: Prednisone

Must not be taking: JAK inhibitors, Strong OAT-3 inhibitors

Disqualifiers: Malignancy, Active infection, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests Baricitinib, an anti-inflammatory medication, on patients with Pyoderma Gangrenosum, a severe skin condition. The medication aims to reduce swelling and pain by blocking enzymes that cause inflammation. Baricitinib is taken orally and is also used to treat conditions like rheumatoid arthritis, atopic dermatitis, and systemic lupus erythematosus.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking certain medications. Participants must discontinue immunosuppressive therapies like cyclosporine and methotrexate at least 4 weeks before starting the study drug. Additionally, there are specific washout periods for biologic therapies, such as 4 weeks for drugs like infliximab and 24 weeks for rituximab.

What data supports the effectiveness of the drug Baricitinib for treating Pyoderma Gangrenosum?

Research shows that Baricitinib, a type of drug called a JAK inhibitor, helped two patients with Pyoderma Gangrenosum achieve complete remission, meaning their skin ulcers healed completely. ^{1 2 3 4 5}

Is baricitinib generally safe for use in humans?

Baricitinib, used for conditions like atopic dermatitis and rheumatic diseases, generally has a favorable safety profile, but there are some risks. It may increase the chance of serious infections, blood clots, and heart issues, especially in people with existing risk factors. However, these risks are often similar to or lower than those seen with other treatments for these conditions. ^{6 7 8 9 10}

How is the drug Baricitinib unique for treating pyoderma gangrenosum?

Baricitinib is unique because it is an oral medication that works by selectively inhibiting Janus kinase 1 and 2, which are enzymes involved in inflammation. This mechanism is different from other treatments for pyoderma gangrenosum, which may not target these specific enzymes. ^{11 12 13 14 15}

Research Team

Alex G Ortega-Loayza, MD, MCR

Principal Investigator

Oregon Health & Science University, Department of Dermatology

Eligibility Criteria

Adults aged 18-99 with Pyoderma Gangrenosum (PG) ulcers, who can travel to OHSU or do video calls for study visits. Women must use birth control or abstain; men must agree not to father children during the trial. Participants should be stable on prednisone and off other immunosuppressives for 4 weeks.

Inclusion Criteria

Willingness to comply with study procedures/requirements

I am a woman aged 18-99, not pregnant, and agree to use birth control or remain abstinent during the study.

I receive weekly wound care at home or a facility.

Exclusion Criteria

Are investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling)

I have had a shingles outbreak within the last 3 months or have had recurrent or widespread shingles.

Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the investigator

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 mg of baricitinib once daily for 24 weeks, along with a stable dose of prednisone, which is tapered based on a pre-established algorithm

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including cytokine gene expression and quality of life measures

12 weeks

Treatment Details

Interventions

• Baricitinib (Janus Kinase (JAK) Inhibitor)

Trial Overview The trial is testing Baricitinib, an oral medication, in adults with PG. It's an open-label study where everyone knows they're getting the drug. The goal is to see if it helps heal skin ulcers better than current treatments.

Participant Groups

Group I: Baricitinib for PG Experimental Treatment 1 Intervention

Subjects with PG will be treated with 4 mg once daily of baricitinib for 24 weeks in addition to starting stable dose (at least 2 weeks) of prednisone at 30 mg daily. Prednisone will be tapered based on a pre-established algorithm assessed by investigator.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

Findings from Research

Tofacitinib, an immunosuppressive agent, showed promising results in treating pyoderma gangrenosum (PG) in a small group of 10 patients who had previously failed an average of four other treatments.

In this study, 40% of patients experienced complete healing of their ulcers, while 60% showed significant clinical improvement, suggesting that tofacitinib could be an effective steroid-sparing option for refractory PG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for the treatment of refractory pyoderma gangrenosum. Orfaly, VE., Kovalenko, I., Tolkachjov, SN., et al.[2021]

Pyoderma gangrenosum is a serious skin condition that often appears as ulcers and is linked to various systemic diseases, typically diagnosed through exclusion and clinical findings.

In two reported cases, chronic skin ulcers consistent with pyoderma gangrenosum completely healed after treatment with the Janus kinase inhibitor baricitinib, suggesting its potential efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor. Scheinberg, M., Machado, LA., M Castro, LG., et al.[2021]

Tofacitinib, a JAK/STAT pathway inhibitor, has shown promising results in treating pyoderma gangrenosum (PG) in three biopsy-proven cases, leading to successful outcomes without relapse during follow-up.

This treatment offers a potential new option for managing PG, which is often challenging due to its tendency to relapse and the need for prolonged steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in pyoderma gangrenosum - A case series. Sathyanarayana, VA., Roy, D., Nagaraju, B., et al.[2023]

In a review of 148 cases of difficult-to-treat pyoderma gangrenosum (PG), it was found that the condition is more prevalent in females and those with inflammatory bowel disease, but most patients healed within a typical timeframe despite needing three or more treatments.

The study suggests that initiating biologic therapies earlier may be beneficial for PG patients, highlighting the need for standardized terminology in the field to improve treatment comparisons and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs. Becker, SL., Velasco, R., Ortega-Loayza, AG.[2023]

Hospitalizations for pyoderma gangrenosum (PG) have increased from 2002 to 2012, with significant predictors including age 40-59, female sex, and multiple chronic conditions, indicating a growing healthcare burden.

Patients hospitalized for PG often face considerable risks, with over half experiencing moderate to major loss of function and a notable association with other health disorders, highlighting the need for effective management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The inpatient burden and comorbidities of pyoderma gangrenosum in adults in the United States. Narla, S., Silverberg, JI.[2021]

Baricitinib, an oral JAK1/JAK2 inhibitor, has a safety profile that reflects the inherent risks of the diseases it treats, with higher rates of infections and serious adverse events observed in patients with rheumatic diseases compared to those with dermatological conditions.

In clinical studies, the incidence of major adverse cardiovascular events (MACE) with baricitinib was lower than that seen with tofacitinib and comparable to tumor necrosis factor inhibitors, indicating a favorable safety profile, especially in hospitalized COVID-19 patients treated for up to 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Bieber, T., Feist, E., Irvine, AD., et al.[2023]

JAK inhibitors, such as tofacitinib, upadacitinib, baricitinib, and abrocitinib, are highly effective for treating conditions like psoriatic arthritis and atopic dermatitis.

Despite their efficacy, JAK inhibitors are associated with increased risks of serious side effects, including venous thromboembolism and cardiovascular events, prompting the FDA to issue additional warning labels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK in the [Black] Box: A Dermatology Perspective on Systemic JAK Inhibitor Safety. Elmariah, SB., Smith, JS., Merola, JF.[2022]

JAK inhibitors, including upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib, have been found to have a generally favorable long-term safety profile for treating various dermatological conditions, based on a review of literature from 2000 to 2023.

The review identified 37 dermatological disorders where JAK inhibitors are supported for use, indicating their potential as effective treatment options for a wide range of skin disorders, including off-label applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. Corbella-Bagot, L., Riquelme-McLoughlin, C., Morgado-Carrasco, D.[2023]

In a phase 3 trial involving 440 adults with moderate-to-severe atopic dermatitis, baricitinib (2 mg) demonstrated a significant efficacy, with 30% of patients achieving a ≥75% reduction in eczema severity at week 16 compared to only 8% in the placebo group.

Baricitinib also showed a favorable safety profile, with no new safety concerns identified over the 16-week study period, indicating it is a viable treatment option for patients who do not respond to topical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). Simpson, EL., Forman, S., Silverberg, JI., et al.[2021]

In a Phase 3 trial with 329 patients suffering from moderate-to-severe atopic dermatitis, baricitinib (4-mg and 2-mg) combined with topical corticosteroids showed significant improvements in health-related quality of life (HRQoL) and work productivity starting as early as Week 2.

Baricitinib 4-mg maintained these improvements through Week 16, demonstrating its efficacy in reducing symptoms and enhancing overall treatment benefits compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. Wollenberg, A., Nakahara, T., Maari, C., et al.[2021]

Baricitinib, an oral medication for moderate-to-severe atopic dermatitis, showed significant improvements in skin severity scores (EASI and SCORAD) as early as week 1 for monotherapy and week 2 for combination therapy, with effects lasting up to 16 weeks.

Patients treated with baricitinib experienced rapid and sustained improvements in quality of life, suggesting that these improvements may exceed what is reflected in traditional severity scores, indicating a potential disconnect between clinical assessments and patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. Thyssen, JP., Bieber, T., Kleyn, CE., et al.[2023]

In a study involving 1598 patients treated with baricitinib 2 mg for moderate-to-severe atopic dermatitis, the overall safety profile was confirmed, with treatment-emergent adverse events occurring in 57.9% of patients compared to 51.6% in the placebo group.

Serious adverse events were infrequent and similar between baricitinib and placebo, with no malignancies or major cardiovascular events reported during the placebo-controlled period, although longer exposure is needed to fully assess risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. King, B., Maari, C., Lain, E., et al.[2022]

In a long-term study involving adults with moderate-to-severe atopic dermatitis, baricitinib combined with topical corticosteroids showed sustained efficacy over 68 weeks, with 26.5% of patients achieving significant improvement in their condition by Week 52.

Both 4-mg and 2-mg doses of baricitinib maintained clinically meaningful results, with higher response rates in the 2-mg group for certain measures, indicating that lower doses can also be effective in managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy (up to 68 weeks) of Baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. Silverberg, JI., Simpson, EL., Thyssen, JP., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Tofacitinib for the treatment of refractory pyoderma gangrenosum. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Tofacitinib in pyoderma gangrenosum - A case series. [2023]

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

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

The inpatient burden and comorbidities of pyoderma gangrenosum in adults in the United States. [2021]

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

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. [2023]

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

JAK in the [Black] Box: A Dermatology Perspective on Systemic JAK Inhibitor Safety. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials. [2023]

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

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). [2021]

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

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. [2023]

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

Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy (up to 68 weeks) of Baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. [2023]