Cyclosporine vs Steroids for DRESS Syndrome

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Southern California

Must be taking: Steroids, Cyclosporine

Disqualifiers: Sepsis, Hepatitis B/C, Tuberculosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on comparing two treatments for DRESS, steroids and cyclosporine, without mentioning changes to other medications.

What data supports the effectiveness of the drug cyclosporine combined with steroids for treating DRESS Syndrome?

Research shows that cyclosporine combined with steroids is more effective than steroids alone in treating Graves' ophthalmopathy, an autoimmune condition. This suggests that cyclosporine may enhance the effectiveness of steroids in managing immune-related conditions. ^{1 2 3 4 5}

Is cyclosporine or steroids safe for treating DRESS syndrome?

Cyclosporine and steroids have been used to treat DRESS syndrome, a serious drug reaction, with some success. Steroids are commonly used but can have side effects like diabetes or psychosis, while cyclosporine has been used in cases where steroids are not effective. Both treatments have been generally well-tolerated, but close monitoring is important due to potential side effects. ^{6 7 8 9 10}

How does the drug combination of Cyclosporine and Steroids differ from other treatments for DRESS Syndrome?

The combination of Cyclosporine and Steroids for DRESS Syndrome is unique because Cyclosporine, known for its use in organ transplantation and autoimmune diseases, works by suppressing the immune system, potentially reducing severe allergic reactions. This approach is different from standard treatments, as it combines the immunosuppressive effects of Cyclosporine with the anti-inflammatory properties of Steroids, offering a novel strategy for managing this condition. ^{2 11 12 13 14}

What is the purpose of this trial?

Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids and cyclosporine. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis. This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS. Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) \< 30 (unless on dialysis in which case the participants will be included).

Eligibility Criteria

Adults with a likely diagnosis of DRESS (a severe skin reaction to drugs) as indicated by a RegiSCAR score over 4 can join this trial. It's not for those who have allergies to steroids or cyclosporine, active hepatitis B/C, sepsis, tuberculosis, or severely reduced kidney function unless they're on dialysis.

Inclusion Criteria

You have a high RegiSCAR score, which suggests you may have a serious skin reaction called DRESS.

Exclusion Criteria

I have active tuberculosis.

My kidney function is low, but I am on dialysis.

You have a confirmed allergy to steroids or cyclosporine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either corticosteroids or cyclosporine based on randomization to compare efficacy in treating DRESS

4-8 weeks

Weekly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including resolution of symptoms and any adverse effects

12 weeks

Monthly visits (in-person or virtual)

Long-term monitoring

Participants are monitored for long-term outcomes such as autoimmune development and viral reactivation

90 days

Treatment Details

Interventions

• Cyclosporine
• Methylprednisolone and Prednisone

Trial Overview The study compares two standard treatments for DRESS: Cyclosporine versus Steroids (Methylprednisolone and Prednisone). This pilot RCT aims to determine which treatment is more effective without additional procedures beyond routine care.

Participant Groups

Group I: Corticosteroids Experimental Treatment 1 Intervention

All Patients start with 500 mg IV Methylprednisolone for 3 days 1. If \>25% improvement (must be \>25% in all involved organs), start the taper regimen 2. If 0-25% improvement (in ≥1 involved internal organ), give 500 mg IV Methylprednisolone for 4 days 1. If no improvement, switch to cyclosporine arm of treatment 2. If 0-25% improvement, give 500 mg IV Methylprednisolone for 3 days i. If labs are down-trending, start the taper regimen ii. If labs are not down-trending, switch to cyclosporine arm of the study c. If \>25% improvement, start the taper regimen Taper Regimen set as: 1. 125 mg IV Methylprednisolone x3 days 2. 1.2 mg/kg PO prednisone x1 week 3. 1 mg/kg PO prednisone x1 week 4. 0.8 mg/kg PO prednisone x1 week 5. 0.6 mg/kg PO prednisone x1 week 6. 0.4 mg/kg PO prednisone x1 week 7. 0.2 mg/kg PO prednisone x1 week 8. 0.1 mg/kg PO prednisone x1 week 9. 0.05 mg/kg PO prednisone x1 week

Group II: Cyclosporine Active Control 1 Intervention

All Patients start with 5 mg/kg/day (3 mg/kg/day if renal impairment) PO divided bid for 7 days (or IV if patient is NPO) 1. If complete resolution, stop cyclosporine and monitor closely for relapse a. If patient relapses, give 5 (3 if renal impairment) mg/kg/day PO divided bid PO for 7 days i. If down-trending, start oral taper regimen ii. If not down-trending, switch to steroid arm 2. If \>25% improvement and labs are down-trending, start the oral taper regimen. 3. If 0-25% improvement, give 5 (3 if renal impairment) mg/kg/day PO divided bid for 3 days 1. If down-trending, start oral taper regimen 2. If not down-trending, switch to steroid arm 4. If no improvement or up-trending labs at 7 days, switch to steroid arm Oral Taper Regimen set as 3 mg/kg PO divided bid for 14 days, then 2 mg/kg PO divided bid for 20 days. If renal impairment, oral taper regimen set as 2 mg/kg PO divided bid for 14 days, then 1 mg/kg PO divided bid for 20 days

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

Approved in European Union as Neoral for:

• Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
• Treatment of severe psoriasis
• Treatment of nephrotic syndrome

Approved in United States as Neoral for:

• Prevention of organ rejection in kidney, liver, and heart transplants
• Treatment of severe rheumatoid arthritis
• Treatment of severe psoriasis

Approved in Canada as Neoral for:

• Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
• Treatment of severe psoriasis
• Treatment of nephrotic syndrome

Approved in Japan as Neoral for:

• Prevention of organ rejection in kidney, liver, and heart transplants
• Treatment of severe rheumatoid arthritis
• Treatment of severe psoriasis

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Findings from Research

In a study involving 12 patients with Graves' ophthalmopathy, treatment with Cyclosporin-A combined with methylprednisolone resulted in slight to moderate improvement in 9 cases.

The findings suggest that methylprednisolone was primarily responsible for the positive effects, while Cyclosporin-A enhanced its effectiveness, even in patients who were resistant to glucocorticoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined cyclosporin-A and methylprednisolone treatment of Graves' ophthalmopathy. Leövey, A., Bakó, G., Szabó, J., et al.[2013]

In a case study of a 27-year-old woman with severe Crohn's disease and refractory Pyoderma gangrenosum (PG), the combination of certolizumab pegol with systemic steroids and tacrolimus led to complete healing of PG after previous treatments failed.

Certolizumab pegol may serve as an effective alternative therapy for PG in patients who cannot tolerate or do not respond to other anti-TNF therapies, highlighting its potential role in managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease. Hurabielle, C., Schneider, P., Baudry, C., et al.[2018]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

Combined cyclosporin-A and methylprednisolone treatment of Graves' ophthalmopathy. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Cyclosporin in autoimmune diseases]. [2007]

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

Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease. [2018]

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

Endocrine ophthalmopathy in a patient under continuous immunosuppressive therapy after cardiac transplantation. [2019]

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

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Comparison of cyclosporine and systemic corticosteroid for treating drug reaction with eosinophilia and systemic symptoms syndrome: A retrospective 20-year single-centre study in South Korea. [2023]

7. Canada pubmed.ncbi.nlm.nih.gov

Cyclosporine in the Treatment of Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome: Retrospective Cohort Study. [2023]

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

Cyclosporine as an alternative immunosuppressant for steroid-resistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. [2023]

9. France pubmed.ncbi.nlm.nih.gov

Ten cases of drug reaction with eosinophilia and systemic symptoms (DRESS) treated with pulsed intravenous methylprednisolone. [2013]

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

How to recognize and manage challenging DRESS cases: Two case reports and a review of the literature. [2022]

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

Neoral-to-Gengraf conversion in renal transplant recipients. [2019]

12. Italy pubmed.ncbi.nlm.nih.gov

[Nephrotic syndrome refractory to conventional therapy]. [2018]

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

Cyclosporin A in renal transplantation: a prospective randomized trial. [2013]

14. Germany pubmed.ncbi.nlm.nih.gov

Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. [2013]