Sequential efgartigimod-rituximab therapy in autoimmune nodopathy: A feasibility report on shortening the washout interval for B-cell depletion.

Diseases associated with antibodies targeting nodal-paranodal cell-adhesion molecules have been recognized as a distinct entity termed autoimmune nodopathy (AN) since 2021. Efgartigimod, a neonatal Fc receptor antagonist, may interfere with the efficacy of monoclonal antibodies. Conventional pharmacokinetic principles suggest that complete elimination of drug interactions requires approximately five half-lives. However, whether this standard applies to FcRn antagonists remains unclear. We report a patient with anti-contactin-associated protein 1 (CASPR1) antibody-mediated AN refractory to intravenous immunoglobulin and plasma exchange. A novel sequential therapy was administered: rituximab was given after one efgartigimod half-life. During one-year follow-up, serum anti-CASPR1 IgG converted from 1:100 to negative, the INCAT score improved from 3/2 to 1/1, the MRC sum score increased from 48 to 54, and CD19+ B-cell count was 0.95/μl one month post-rituximab. B-cell depletion was sustained. This novel sequential strategy achieved sustained antibody reduction without compromising B-cell depletion, suggesting that the required washout period for FcRn antagonists prior to monoclonal antibody administration may be shorter than traditional pharmacokinetic models predict. It represents a feasible and promising therapeutic option for AN patients unresponsive to IVIG and PE, although further validation in larger cohorts is needed.