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Anti-IL-5 Therapy in Bullous Pemphigoid (BP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01705795
Recruitment Status : Completed
First Posted : October 12, 2012
Last Update Posted : February 28, 2017
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
Randomized, placebo-controlled, double-blind study evaluating the effect of anti-IL-5-therapy in patients with bullous pemphigoid. The primary study objective is to determine the efficacy of an anti-IL-5 monoclonal antibody therapy, administered as 750mg mepolizumab, in patients with bullous pemphigoid.

Condition or disease Intervention/treatment Phase
Pemphigoid, Bullous Drug: Mepolizumab (a-IL-5 antibody) Drug: Placebo Phase 2

Detailed Description:


Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease. It characteristically affects the elderly (>70 years) with an annual incidence of 5 to 35 per million. This is comparable with the incidence of eosinophilic esophagitis that we determined with approximately 14 per million. Eosinophilic esophagitis has been recognized as an emerging medical problem and, consequently, several studies with anti-IL-5-antibodies have been performed and are still ongoing. It should be noted, however, that, in contrast to eosinophilic esophagitis, the incidence of BP is dramatically increasing with an average of 17% per year. Moreover, with the increase of the proportion of the elderly in the industrialized world, the medical problems associated with BP will even be more visible in the near future. For instance, patients with BP have an increased mortality risk of 2.3. In the US, an increase in mortality of BP patients has been noticed from 1979 to 2002. Taken together, BP is a frequent disease that affects mostly the elderly.

BP often starts with extremely pruritic skin lesions resembling eczema or urticaria before vesicles and blisters arise. In 10-30% of patients, BP also involves the oral mucosa. Disease severity can be determined by means of the autoimmune bullous skin disorder intensity score (ABSIS) that evaluates the involved area as well as the disease activity. The disease is due to an autoimmune response to structural components of junctional adhesion complexes leading to the damage of the dermal-epidermal junction with subepidermal blister formation. Specifically, autoreactive B and T cell responses against the hemidesmosomal antigens BP180 and BP230 have been identified. Serum levels of autoantibodies to BP180 reflect the disease severity and activity. The T cells are memory CD4+ cells producing both Th1 and Th2 cytokines, mostly IL-4, IL-5 and IL-13. IL-5 as well as eotaxin are abundantly found in blister fluids. The production of IL-5 is indeed associated with blood eosinophilia and significant eosinophil infiltration in the skin of BP patients. Eosinophils are thought to be critically implicated in blister formation by releasing toxic granule proteins (ESP, MBP) and proteolytic enzymes.

Systemic corticosteroids have been widely used for the treatment of BP. Nevertheless, the use of steroids is limited by their side effects. in therapy-resistant cases, immunosuppressive drugs such as azathioprine, chlorambucil, cyclophosphamide, cyclosporine, methotrexate, mycophenolate mofetil are employed, but their corticosteroid-sparing effect and overall benefit in BP is highly disputed. 70% of the relapses are usually observed within three months, 85% within 6 months after stopping therapy.

Since eosinophils are characteristically found in the skin at early stages of the disease before blisters occur and contribute to tissue damage, targeting eosinophils by reducing their number and activation might thus be a promising alternative therapeutic approach. Anti-IL-5 antibody therapy has been shown to be effective in depleting eosinophils, e.g. in diseases such as eosinophilic esophagitis and hypereosinophilic syndrome.


To determine the safety and efficacy of mepolizumab in patients with bullous pemphigoid.


clinical trial with 750 mg mepolizumab over three months, evaluate time period from start of therapy until relapse, ABSIS-Score, Pruritus Score, Antibody levels, immuno pathological evaluation of skin biopsy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Anti-IL-5 Therapy in Bullous Pemphigoid. Randomized, Placebo-controlled, Double-blind Study Evaluating the Effect of Anti-IL-5 Therapy in Patients With Bullous Pemphigoid.
Actual Study Start Date : February 13, 2013
Actual Primary Completion Date : January 31, 2017
Actual Study Completion Date : January 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus
Drug Information available for: Mepolizumab

Arm Intervention/treatment
Active Comparator: Mepolizumab
Mepolizumab 750 mg four times one month apart.
Drug: Mepolizumab (a-IL-5 antibody)
750mg mepolizumab four times over four months

Placebo Comparator: Placebo
Placebo (saline) four times one month apart
Drug: Placebo
Nacl four times over four months

Primary Outcome Measures :
  1. Time period (in days) from start of therapy until relapse, mepolizumab vs placebo [ Time Frame: Before, at 3-9 months ]

Secondary Outcome Measures :
  1. Changes of BP severity score over time (ABSIS) [ Time Frame: At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months) ]
  2. Changes of pruritus score (visual analog scale) [ Time Frame: At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months) ]
  3. Changes of BP-antibody titers over time [ Time Frame: At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months) ]
  4. Number of patients with AE, severity of AE [ Time Frame: At baseline, during therapy (expected to be ca. 4 months), follow up (expected to be ca. 9 months) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men, women >18 years
  • Active BP (diagnosed by typical clinical picture and skin biopsy)
  • Must give written informed consent

Exclusion Criteria

  • Patients with other skin disease
  • Patients with severe diseases of other organ systems
  • Systemic treatment for BP
  • Topical therapy with corticosteroids and other anti-inflammatory substances
  • For female patients, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception (defined as methods with <1% failure rate)
  • Female patients who are currently pregnant or breast-feeding
  • Current abuse of alcohol and/or drugs
  • History of or a new diagnosis or treatment of an invasive malignancy within 5 years of enrollment. Patients with a history of treated squamous cell and/or basal cell carcinomas limited to the skin are not excluded.
  • History of recurrent clinically significant infection
  • Congenital or acquired immunodeficiency syndrome
  • Current enrollment in any other investigational drug study
  • Previous participation in this study or previous studies with mepolizumab
  • Hypersensitivity to mepolizumab or its constituents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01705795

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Dep. of Dermatology, Bern University Hospital
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
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Principal Investigator: Dagmar Simon Inselspital, Bern University Hospital
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Responsible Party: University Hospital Inselspital, Berne Identifier: NCT01705795    
Other Study ID Numbers: 191/11
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: February 28, 2017
Last Verified: February 2017
Additional relevant MeSH terms:
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Pemphigoid, Bullous
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs