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Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa

Sponsor
Elena Gonzalez Brant, MD (Other)
Overall Status
Completed
CT.gov ID
NCT03275870
Collaborator
University of Pittsburgh (Other)
17
Enrollment
1
Location
1
Arm
21
Actual Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pilot Study of Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa
Actual Study Start Date :
Sep 28, 2017
Actual Primary Completion Date :
Jun 30, 2019
Actual Study Completion Date :
Jun 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Hydroxychloroquine treatment

Hydroxychloroquine 200mg BID for 6 months

Drug: Hydroxychloroquine
Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
Other Names:
  • Plaquenil

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Disease Severity [6 months]

      Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome

    Secondary Outcome Measures

    1. Change in Quality of Life [6 months]

      Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Pittsburgh Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • Elena Gonzalez Brant, MD
    • University of Pittsburgh

    Investigators

    • Principal Investigator: Elena M Gonzalez Brant, MD, University of Pittsburgh

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Elena Gonzalez Brant, MD, Principal Investigator, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03275870
    Other Study ID Numbers:
    • STUDY19050057
    First Posted:
    Sep 8, 2017
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Hidradenitis Suppurativa
    Hidradenitis
    Hydroxychloroquine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Hydroxychloroquine Treatment
    Arm/Group Description Hydroxychloroquine 200mg BID for 6 months Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
    Period Title: Overall Study
    STARTED 17
    COMPLETED 3
    NOT COMPLETED 14

    Baseline Characteristics

    Arm/Group Title Hydroxychloroquine Treatment
    Arm/Group Description Hydroxychloroquine 200mg BID for 6 months Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
    Overall Participants 17
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    38.9
    Sex: Female, Male (Count of Participants)
    Female
    14
    82.4%
    Male
    3
    17.6%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    14
    82.4%
    Black
    3
    17.6%
    Region of Enrollment (participants) [Number]
    United States
    17
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Disease Severity
    Description Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Hydroxychloroquine Treatment
    Arm/Group Description Hydroxychloroquine 200mg BID for 6 months Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
    Measure Participants 3
    Baseline sartorius score
    23.3
    (16.2)
    6 month sartorius score
    17.7
    (14.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Hydroxychloroquine Treatment
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.042
    Comments p value <0.05 used as threshold for significance
    Method t-test, 2 sided
    Comments
    2. Secondary Outcome
    Title Change in Quality of Life
    Description Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Hydroxychloroquine Treatment
    Arm/Group Description Hydroxychloroquine 200mg BID for 6 months Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
    Measure Participants 3
    Baseline DLQI score
    14.7
    (11)
    6 month DLQI score
    6
    (7.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Hydroxychloroquine Treatment
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments P value of <0.05 used as threshold for significance
    Method t-test, 2 sided
    Comments

    Adverse Events

    Time Frame 13 months
    Adverse Event Reporting Description Patients were periodically asked about side effects by a telephone call 1 month after starting treatment, at the 3 and 6 month follow up visit. They were evaluated for blurred vision, changes in vision, diarrhea, nausea, vomiting, headache, pruritus, anorexia and abdominal pain
    Arm/Group Title Hydroxychloroquine Treatment
    Arm/Group Description Hydroxychloroquine 200mg BID for 6 months Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
    All Cause Mortality
    Hydroxychloroquine Treatment
    Affected / at Risk (%) # Events
    Total 0/17 (0%)
    Serious Adverse Events
    Hydroxychloroquine Treatment
    Affected / at Risk (%) # Events
    Total 0/17 (0%)
    Other (Not Including Serious) Adverse Events
    Hydroxychloroquine Treatment
    Affected / at Risk (%) # Events
    Total 6/17 (35.3%)
    Eye disorders
    blurred vision 1/17 (5.9%) 1
    Gastrointestinal disorders
    Nausea 2/17 (11.8%) 2
    Nervous system disorders
    headache 1/17 (5.9%) 1
    Psychiatric disorders
    Depression 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders
    urticaria 1/17 (5.9%) 1

    Limitations/Caveats

    We did not reach the target number of participants needed to achieve target power and statistically reliable results leading to unreliable or uninterpretable data.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Elena Gonzalez Brant, PI
    Organization Beth Israel Lahey Health
    Phone 6173191221
    Email emgbrant@gmail.com
    Responsible Party:
    Elena Gonzalez Brant, MD, Principal Investigator, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03275870
    Other Study ID Numbers:
    • STUDY19050057
    First Posted:
    Sep 8, 2017
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020