Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa

NCT ID: NCT03275870

Last Updated: 2020-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2019-06-30

Brief Summary

Hidradenitis suppurativa (HS) is an under-recognized and debilitating disease. Patients suffer from recurring painful abscesses and scarring in their armpits, under the breasts, groin and other areas of the body. The cause of the disease is still unknown and common treatments are only sometimes effective. Overactivity of the immune system has been associated with HS and molecules that cause inflammation have been found in the skin from people with HS. Current therapies have long-term risks including antibiotic resistance and the investigators aim to find new safe and effective therapies for HS.

Hydroxychloroquine is a medication that has been used safely in other diseases for many years. The investigators believe that hydroxychloroquine has the potential to improve HS through multiple mechanisms. Patients enrolled in this study will be treated with hydroxychloroquine for 6 months. The investigators also aim to look at the blood of patients with HS to look for inflammatory molecules that we could possibly target for the treatment of HS. Blood samples will be taken at baseline and following 6 months of treatment.

Detailed Description

Hidradenitis suppurativa is a debilitating and mutilating disease and its pathogenesis is still poorly understood. It involves the development of recurrent, painful nodules in intertriginous areas that become inflamed, form abscesses that may rupture, and develop chronic fistula tracts. The cause of hidradenitis suppurativa (HS) is thought to be multifactorial and may begin with follicular occlusion and rupture, leading to a cascade of inflammatory responses in susceptible individuals. The disease has been associated with high body mass index, smoking and genetic predisposition. There is a known association between HS and the metabolic syndrome, an association that remains after controlling for body mass index. HS predominantly affects women and ethnic minorities and the prevalence is thought to be as high as 2%, although embarrassment and lack of awareness may lead to an underestimate of the true burden of disease.

Although HS is a fairly common disease, relatively little is understood about its pathogenesis. Immune dysregulation is thought to play a role in disease development. Increased levels of interleukin (IL)-12, IL-17, IL-23, tumor necrosis factor α, IL-10 and IL-1β were found to be expressed in lesional skin of HS patients. Recent studies have also identified elevated levels of IL-17 in the serum of patients with HS.

HS is associated with a significant impact on patient quality of life. Patients suffer from both the physical and psychological impact of disease. Many therapies have been used to treat HS, from topical antibiotics to oral retinoids to radical surgeries, but all have limited efficacy. Despite efforts to control disease, many patients live with chronic wounds and disability. The decision about appropriate therapy for HS, especially in the early stages, is mainly based on expert opinion, anecdotal evidence, and small studies. Topical and systemic antimicrobial treatments are often used as first line therapies, although studies have repeatedly shown that the abscesses of HS are sterile or contain only normal flora. The mechanism of improvement with antimicrobials may be through alterations in the local microbiome. Significant improvement in disease has been seen with dual therapy with twice daily use of 300mg rifampicin and 300mg clindamycin, neither of which have an FDA indication for use in HS. Doxycycline is used frequently in HS, but little evidence supports this. Despite success with the above therapies, the risk of antimicrobial resistance is real, and is increased with frequent and prolonged use of these medications in HS. Teratogenic effects, gastrointestinal upset, and photosensitivity with use of tetracyclines, risk for clostridium difficile colitis with clindamycin, and antimicrobial resistance with rifampicin highlight a need for safer and effective therapeutic options for the treatment of early HS.

For more advanced disease (Hurley stage II and III), the tumor necrosis factor inhibitor adalimumab is the only FDA approved biologic treatment for HS. It has shown promise in severe disease, but only ~50% of patients achieved a clinical response at 12 weeks, and this clinical response declined over time. Additionally, newer biologic therapies have been used in small numbers of patients with HS with variable results. Importantly, the cost of these medications is considerable.

Hydroxychloroquine, initially developed as an antimalarial, has been used successfully for over 70 years in the treatment of autoimmune disease. Its mechanism of action is still poorly understood, but it has been shown to have many varied immunomodulatory properties. Evidence suggests that hydroxychloroquine has an effect on inflammatory disease through decreasing levels of TNFα and Th-17 cytokines (including IL-6, IL-17, and IL-22). Additionally, studies have shown a beneficial effect of hydroxychloroquine on lipid metabolism and glucose. Patients with rheumatoid arthritis (which similarly to HS has an independent association with cardiovascular disease) who were treated with hydroxychloroquine had an overall decreased incidence of cardiovascular events. Hydroxychloroquine has a relatively benign safety profile, with retinopathy being the most concerning long term side effect. The retinopathy caused by hydroxychloroquine is reversible if identified early, and standard protocols for the use of this medication include yearly ophthalmologic examination.

Patients with HS suffer daily from the physical and psychological effects of their disease. Despite insufficient data about disease progression and prognosis, early intervention with safe and effective therapies is our goal. Hydroxychloroquine has never been used to treat HS, but the good safety profile, based on many years of usage in other autoimmune diseases, and known ability to modify many of the aberrant metabolic and inflammatory components of HS make it an ideal candidate therapy for this debilitating disease.

Research activities:

1. Treatment with hydroxychloroquine 200mg twice daily. Treatment length will be 6 months. Patients will be allowed to continue or initiate use of topical therapies during the study.

2. Telephone call to assess toxicity after 1 month of treatment

3. Assessment of hidradenitis suppurativa disease activity using Sartorius scoring at baseline, and after 3 and 6 months of treatment

4. Collection of patient serum at baseline and after 6 months of treatment

5. Quality of life questionnaire at baseline, 3 and 6 months

6. Follow up telephone call at ~9 and 12 months (3 and 6 months after therapy completion) to assess for toxicity

7. Baseline ophthalmologic exam for patients on hydroxychloroquine will be conducted within the first year of treatment

Conditions

Hidradenitis Suppurativa; Hidradenitis; Acne Inversa; Boils; Follicular Occlusion Triad; Follicular Occlusion Tetrad

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hydroxychloroquine treatment

Hydroxychloroquine 200mg BID for 6 months

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months

Interventions

Hydroxychloroquine

Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months

Intervention Type: DRUG

Other Intervention Names

Plaquenil

Eligibility Criteria

Inclusion Criteria

• Patients with hidradenitis suppurativa Hurley stage I or II

Exclusion Criteria

• Current systemic immunosuppression, current use of biologic medication or use of these medications in the prior 3 months, patients with known retinal disease, hepatic disease (HCV, cirrhosis, aspartate aminotransferase or alanine aminotransferase > 2 times the upper limit of normal), psoriasis, porphyria cutanea tarda, platelets < 50,000/ul, leukocytes <4000/ul, or Hb<8g/dl), pregnant patients or women trying to conceive

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Elena Gonzalez Brant, MD

OTHER

Sponsor Role: lead

Responsible Party

Elena Gonzalez Brant, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Elena M Gonzalez Brant, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STUDY19050057

Identifier Type: -

Identifier Source: org_study_id