A Single Cycle of Intravenous Immunoglobulin as Adjuvant to Rituximab in Patients With Pemphigus: A Retrospective Cohort Study at a Tertiary Referral Center

Pemphigus is a critical autoimmune skin condition mediated by pathogenic autoantibodies mainly against desmoglein (Dsg)1 and Dsg3, and is traditionally managed with systemic corticosteroids and immunosuppressants.The revolutionary introduction of rituximab (RTX) has opened up a new era of pemphigus treatment by enabling treatment strategies to specifically target CD20+ B cells.Studies have highlighted the superior efficacy of RTX combined with systemic corticosteroids, making this therapy first-line treatment for pemphigus patients.Currently, the main challenge for pemphigus management is to maximize efficacy while preventing relapses and reducing risks over the course of the disease.

RTX achieves maximum effect typically at 4-8 weeks post-treatment, and is associated with an elevated risk of infection.On the other hand, intravenous immunoglobulin (IVIg), historically employed for the management of refractory pemphigus, is appreciated for its rapid action and lack of added immunosuppressive risk.It has also been shown to induce long-term clinical remission, and continues to serve as a rescue therapy for difficult cases.

While there have been reports on the successful use of RTX and concomitant IVIg for treating refractory pemphigus, there is a lack of extensive research weighing the pros and cons of adding IVIg to the currently recommended RTX regimen (Rheumatoid arthritis protocol, RAP). To investigate the efficacy and safety of this combined therapy, we conducted an retrospective cohort study to evaluate the impact of incorporating IVIg into the RTX and systemic corticosteroid treatment protocol for pemphigus patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Rituximab (RTx); Pemphigus Disease; Intravenous Immunoglobulin

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients who had a clinical presentation of active pemphigus combined with immunological or pathological evidence, and received rituximab and systemic corticosteroids.

Description

Inclusion Criteria:

1. Patients' files between January 1st, 2019, and December 31st, 2024 from department of dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
2. with a diagnosis of pemphigus vulgaris or foliaceus in active stage based on guideline indicators, including typical clinical presentation, positive direct immunofluorescence microscopy findings, and/or detection of serum anti-Dsg3 and/or Dsg1 immunoglobin (Ig)G autoantibodies
3. treated with RTX in association with oral corticosteroids
4. with a follow-up of at least 48 weeks after RTX treatment initiation

Exclusion Criteria:

1. with a diagnosis of other variants of pemphigus (e.g., paraneoplastic pemphigus, herpetiform pemphigus, IgA pemphigus);
2. concomitant use of other immunosuppressants (e.g., azathioprine, mycophenolate mofetil, methotrexate)
3. previous administration with IVIg for other indications within 12 weeks

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
RTX group; Adult patients receiving rituximab and systemic corticosteroids without adjuvant IVIg
RTX+IVIg group; Adult patients receiving rituximab and systemic corticosteroids with adjuvant IVIg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
numbers of patients under disease control	according to Pemphigus S2 Guideline, patients' new lesions cease to form and established lesions begin to heal	week 4, 8, 12, 24, 36, 48 after treatment
Number of patients with relapses	according to Pemphigus S2 Guideline，patient who has achieved disease control appears ≥3 new lesions/month that do not heal spontaneously within 1 week, or patient's established lesions extend	week 4, 8, 12, 24, 36, 48 after treatment
Adverse event		week 4, 8, 12, 24, 36, 48 after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
peripheral CD19+ cell counts	week 4, 8, 12, 24, 36, 48 after treatment
Serum rituximab concentration	week 4, 8, 12, 24, 36, 48 after treatment
immunoglobulin levels	week 4, 8, 12, 24, 36, 48 after treatment
serum anti-Dsg1 and Dsg3 autoantibody levels	week 4, 8, 12, 24, 36, 48 after treatment
Serum anti-rituximab antibody concentration	week 4, 8, 12, 24, 36, 48 after treatment

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Estimated): February 2, 2026
• Study Completion (Estimated): February 2, 2026

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Rituximab; Adverse effect; IVIg; Pemphigus
• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vesiculobullous; Pemphigus
• Other Study ID Numbers: MR-31-25-027185