TOPLINE:

In an emulated target trial involving patients with pemphigus, rituximab monotherapy was associated with a lower 5-year overall risk for cancer and solid malignancies than mycophenolate mofetil (MMF) or azathioprine (AZA).

METHODOLOGY:

• Using the TrinetX database, researchers conducted an emulated target trial that included 2136 patients with pemphigus who received their first prescription for MMF/AZA or rituximab within a year of diagnosis between 2017 and 2025.
• The researchers performed 1:1 propensity score-matched analysis with 1068 patients in each treatment group. The median age was 53-54 years; nearly 50% were women, 42% were men, and sex was unknown for the remainder; 47%-48% were White, 8%-9% were Black, and 8%-9% were Asian individuals.
• Patients with paraneoplastic pemphigus or any prior malignancy were excluded, and participants were analyzed according to their initial treatment assignment to emulate an intention-to-treat approach.
• Primary outcomes included hematologic and solid organ malignancies observed over 5 years.

TAKEAWAY:

• Rituximab was associated with a lower overall 5‑year risk for cancer than MMF/AZA (hazard ratio [HR], 0.507; 95% CI, 0.311-0.824); this corresponded to a 5‑year number needed to harm for MMF/AZA vs rituximab of 41.
• Rituximab-treated patients had a reduced risk for solid organ malignancies (HR, 0.427; 95% CI, 0.234-0.777).
• No significant difference was observed in the risk for hematologic malignancies between the rituximab and MMF/AZA groups (HR, 0.766; 95% CI, 0.308-1.905).

IN PRACTICE:

“In the absence of randomized controlled trials on long-term cancer risk, these results provide real-world evidence of a decreased rate of malignancy in patients with pemphigus treated with RTX [rituximab] compared to those treated with MMF or AZA,” the authors wrote. These findings, they added, can help “inform treatment decisions in pemphigus care, addressing a knowledge gap in the comparative long-term safety profiles of these immunosuppressive therapies.” While rituximab is recommended as a first-line treatment for moderate-to-severe pemphigus vulgaris, they pointed out, immunosuppressants such as MMF and AZA “remain widely used.”

SOURCE:

The study was led by Arjun Mahajan, MS, Harvard Medical School, Boston, and was published online on April 7 as a brief report in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study was underpowered to assess combination therapy and risks for individual cancer types. It lacked sufficient clinical detail to identify pemphigus subtypes. The platform did not permit formal testing of the proportional hazards assumption. Additionally, the number needed to harm estimates could have been biased by censoring, and residual confounding from unmeasured factors could not be excluded, limiting causal inference.

DISCLOSURES:

This study did not receive any specific funding. The authors disclosed having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.