IVIG With Rituximab vs Rituximab as First Line Treatment of Pemphigus

  • STATUS
    Recruiting
  • days left to enroll
    9
  • participants needed
    20
  • sponsor
    The University of Hong Kong
Updated on 19 February 2024
remission
corticosteroids
rituximab
immunosuppressive agents
immunoglobulins
immunomodulators
immunosuppressants
autoimmune disease
prednisolone
immunoglobulin
igiv
elisa
intravenous immunoglobulin
enzyme-linked immunosorbent assay
tositumomab
immunoglobulin g
anti-cd20 antibody
acantholysis
pemphigus
mucosal biopsy
indirect immunofluorescence
direct immunofluorescence

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, pemphigus vulgaris (pv), pemphigus vulgaris (pv)
Age 18years - 70years
Treatment Rituximab, IVIg
Clinical Study IdentifierNCT04400994
SponsorThe University of Hong Kong
Last Modified on19 February 2024

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 B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C (HCV) serology at screening
Blood test positive for HIV
Signs of active infection on CXR
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
Inherited or acquired severe immunodeficiency
History of malignancy
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
Past history of osteomyelitis, or fasciitis, septic arthritis within the last one year
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
Patients with history of allergy or adverse events to IVIG or rituximab treatment10
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

Study AnnotationsStudy Notes

Notes added here are public and can be viewed by anyone. Notes added here are only available to you and those who you share with.

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note
  • abc Select a piece of text.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.