To characterize the immunological read out, e.g. the immune cell compartments, and antibodies of patients with autoimmune bullous diseases during rituximab treatment and during relapses.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
B-cell phenotype, B-cell repertoire, including number of expanded B-cell clones
Secondary outcome
Laboratory serum and cellular parameters:
• Antigen-specific B cell receptor sequences
• RNA expression profile of antigen-specific B-cells
• Peripheral blood mononuclear cells (PBMC*s)
• Free light chains (FLCs) as a biomarker for plasmacells
• Anti-desmoglein 1 and 3 antibodies
• Antibodies against the noncollagenous 16A domain of BP180 (NC16A) and BP230
• Serum B-lymphocytes, T-lymphocytes
• Serum total IgG and subclasses
• Glycosylation status and binding characteristics of IgG antibodies
Clinical parameters:
• Response outcomes were defined according to international consensus and
measured by the early endpoint disease control (DC), and the
late endpoints partial remission (PR), complete remission (CR), and the
number of relapses.
• Pemphigus Disease Area Index (PDAI)
• Bullous Pemphigoid Disease Area Index (BPDAI)
• Mucous Membrane Pemphigoid Disease Area Index (MMPDAI)
• Adjuvant immunomodulatory or immunosuppressive treatment
• Dermatology Life Quality Index (DLQI)
• Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL)
• Visual Analogue Scale (VAS) pain and itch
• Geriatric 8 (G-8) Score in patients above 50 years
Background summary
Rituximab is a chimeric murine-human monoclonal antibody that binds and targets
the CD20 antigen of B-lymphocytes. It is used to eliminate B-cell
immunoreactivity in autoimmune bullous diseases, including pemphigus diseases,
bullous pemphigoid and mucous membrane pemphigoid. Recently rituximab is
approved for pemphigus vulgaris. Understanding the mechanisms of action of
B-cell targeted therapy is essential to optimize tailored therapeutic
strategies and to get more knowledge about the predictive factors for disease
relapses during and after treatment. The aim of this study is to prospectively
collect multi-layered standardized clinical data, patient-reported outcome
measures (PROMS) and biosamples in patients with autoimmune bullous diseases to
allow for standardized comparison of the immunological processes during
different phases of disease activity.
Study objective
To characterize the immunological read out, e.g. the immune cell compartments,
and antibodies of patients with autoimmune bullous diseases during rituximab
treatment and during relapses.
Study design
Explorative, prospective observational cohort study.
Study burden and risks
Participation in this study has negligible risk because the only intervention
done is venapuncture to obtain blood. In principal, study visits will be
planned to coincide with standard clinical visits to decrease the burden for
participants.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
• Age of 18 years or older.
• Diagnosis of pemphigus, based on the following criteria: clinical features
suggestive of pemphigus vulgaris or pemphigus foliaceus; a histological image
of intraepidermal acantholysis; and/or deposition of IgG, complement component
3, or both on the keratinocyte membrane detected by direct immunofluorescence
• Diagnosis of pemphigoid, based on the following criteria: linear depositions
of IgG, IgA, IgM, or C3c along the BMZ by direct immunofluorescence microscopy
(DIF) and/or positive indirect immunofluorescence microscopy (IIF) on
salt-split skin (SSS), in combination with clinical presentation,
histopathological findings, or other immunoserological tests compatible with
the diagnosis of a pemphigoid disease.
• Administration of rituximab according to the following protocol: two infusion
of 1000mg within an interval of two weeks, followed by 500mg at month 6 and
month 12, or in patients with severe pemphigus 1000mg at month 6, or in
patients who are not in complete remission two infusions of 1000mg two weeks
apart.
Exclusion criteria
• Patients under the age of 18 years.
• Plasma exchange, plasmapheresis or immunoadsorption within the last 3 months
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL76959.042.21 |