IVIG With Rituximab vs Rituximab as First Line Treatment of Pemphigus

  • STATUS
    Recruiting
  • End date
    Dec 31, 2024
  • participants needed
    20
  • sponsor
    The University of Hong Kong
Updated on 7 October 2022
corticosteroids
remission
rituximab
prednisolone
immunosuppressants
autoimmune disease
immunoglobulins
immunoglobulin g
intravenous immunoglobulin
enzyme-linked immunosorbent assay
anti-cd20 antibody
mucosal biopsy

Summary

Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.

Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Early use of rituximab was associated with better clinical outcomes, hence combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.

In this study, investigators will evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.

Description

Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.

Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Furthermore, early use of rituximab was associated with associated with better clinical outcomes. Moreover, combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.

Cost effectiveness is an important issue and while combination of IVIG and rituximab has been advocated, the cost of such treatment is substantial and whether it poses any benefit over rituximab alone, or with other more conventional immunosuppressive agents, has not been established. Both treatment approaches have been previously published in high impact journals.

In this study, investigators aim to evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published. Apart from complete remission and adverse effects, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.

Details
Condition Pemphigus
Treatment Rituximab, IVIG
Clinical Study IdentifierNCT04400994
SponsorThe University of Hong Kong
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent obtained from patient
Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
Newly or recently diagnosed (less than 18 months) diagnosed pemphigus vulgaris or pemphigus foliaceus based on clinical features; histological features of acantholysis via skin or mucosal biopsy; and intercellular staining pattern of indirect immunofluorescence or serological detection of DSG 1 or DSG 3 by enzyme-linked immunosorbent assay (ELISA)
Moderate to severe active disease, as defined by overall PDAI >= 15 or skin involvement BSA>= 5%. 9 [Annex 1]
Receiving standard-of-care oral prednisolone up to 1.5 mg/kg/day
Women who are sexually active and not postmenopausal, agreement to remain abstinent or use 2 effective methods of contraception
Ability to comply with study protocol as deemed by investigator's assessment

Exclusion Criteria

Age <18 or >70
Pregnant women or nursing mother
Already diagnosed pemphigus patients diagnosed > 18 months
Non-consenting patients, or patient who cannot be followed up regularly
Patient with history of serious allergy or anaphylactic reaction to monoclonal antibody treatment
Severe heart failure (NYHA Class III or IV)
Unstable angina or myocardiac infarction within last 3 months or post-infarction heart failure
Anaemia (haemoglobin <10g/dL), Neutropenia (<1000/mm3), Lymphopenia (<900/mm3), thrombocytopenia (<100,000/mm3)
Renal insufficiency eGFR <60
Liver insufficiency of ALT/ALT > 2 times normal limit range
Positive test results for hepatitis C (HCV) serology at screening Patients who are HepBs Ag positive, or HepBs Ag negative and anti-HepBc Ab - positive: Patients who are HepBs Ag positive - will be started on entecavir 0.5mg daily, and will be referred to a gastroenterologist for further follow up
Blood test positive for HIV
Patients who are HepBs Ag negative, and HBc Ab positive, with detectable HepB DNA levels -
Signs of active infection on CXR
will be started on entecavir 0.5mg daily, and will be referred to a gastroenterologist for
further follow up
Patients who are HepBs Ag negative, HBc Ab positive, with no detectable HepB DNA levels -
Inherited or acquired severe immunodeficiency
will be started on entecavir 0.5mg daily, and will be continued on entecavir for at least
History of malignancy
months after completion of last dose of rituximab
Past history of osteomyelitis, or fasciitis, septic arthritis within the last one year
Positive interferon gamma release assay Quantiferon or T.Spot TB test: must be treated
with at least 4 weeks post initiation of isoniazid or other TB therapy
Patients with history of allergy or adverse events to IVIG or rituximab treatment10
Patient with active severe infection (excluding fungal infections of the nail), which
has required antibiotic treatment within 2 week prior to study enrolment
Infection requiring hospitalisation or intravenous antibiotic treatment within the
last 8 weeks prior to enrolment
Patients with drug induced pemphigus. A thorough medication history will be taken to
rule out drug induced pemphigus including D-penicillamine, angiotensin-converting
enzyme inhibitors, angiotensin receptor blockers and cephalosporins
Evidence of any new or uncontrolled concomitant disease that in the investigators'
judgement would preclude the patients participation
Treatment with intravenous immunoglobulins, plasmaphoresis within the last 8 weeks
prior to randomization
Previous treatment with rituximab or any monoclonal antibody inducing profound
lymphopenia
Treatment with live or attenuated vaccine within the last 28 days prior to
randomization
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