IVIG With Rituximab vs Rituximab as First Line Treatment of Pemphigus

This is an interventional treatment trial for Pemphigus focused on measuring Pemphigus, intravenous immunoglobulins, rituximab Read More

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.

Patients who are HepBs Ag negative, and HBc Ab positive, with detectable HepB DNA levels - 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 - will be started on entecavir 0.5mg daily, and will be continued on entecavir for at least 18 months after completion of last dose of rituximab.

• 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