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

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.

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