Antirituximab Antibodies in Patients With Pemphigus Treated With Rituximab

The antirituximab antibodies (ARAs) often found in patients with pemphigus treated with rituximab (RTX) are not typically linked with patient outcomes, according to findings from post hoc analysis published in the Journal of the American Medical Association Dermatology. A greater risk for relapse may occur in patients with concurrent ARAs, incomplete B-cell depletion, persistent serum anti-desmoglein 3 antibody (DSG3 Abs), and low RTX concentration, it was found.

Although rituximab was approved by the FDA for treatment of pemphigus vulgaris in 2018, the clinical implications of antirituximab antibodies remains uncertain. A significant percentage of patients relapse in the first 12 months following treatment, and the relapse rate increases over time. Investigators sought to examine the occurrence rate of ARAs in patients treated with RTX for pemphigus and determine the association of ARAs with relapse and complete remission (CR).

They conducted a post hoc analysis of the Ritux3 trial (conducted in 25 dermatology departments in France, January 2010 through December 2015) that included 42 patients diagnosed with moderate to severe pemphigus of whom 9 relapsed within the first 12 months, received additional infusions, and were excluded from analysis. Of the remaining 33 patients (22 women), 13 (11 women) developed ARAs within the first year.

In addition, 2 patients relapsed after the first year, and 31 sustained CR through 3 years. Sustained rate of CR was similar in patients with ARAs (11 of 13) and without ARAs (20 of 20) as were B-cell depletion and RTX levels. Higher anti-DSG3 Abs were seen in those patients without ARAs than those with ARAs. The 2 patients who relapsed after the first year had ARAs, incomplete B-cell depletion, higher anti-DSG3 Abs level, and undetectable RTX level compared with the other 11 patients with ARAs who sustained CR or compared with the 20 patients without ARAs.

Investigators acknowledged analysis limitations in the underpowered sample size of patients with late relapse, the mechanism of action of the ARAs could not be determined, and the use of an anti-CD-19 instead of an anti-20 monoclonal antibody.

They concluded that their results suggest ARAs are often found in patients with pemphigus vulgaris who have been treated with RTX, but that the ARAs are typically not associated with patient consequences. They noted that, “Only a few patients with the combination of ARAs, low RTX concentration, incomplete B-cell depletion, and persistent serum anti-DSG3 Abs seem at high risk of relapse.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Lemieux A, Maho-Vaillant M, Golinski ML, et al. Evaluation of clinical relevance and biological effects of antirituximab antibodies in patients with pemphigus. JAMA Dermatol. Published online June 22, 2022. doi:10.1001/jamadermatol.2022.2149