Long‐Term Safety and Efficacy of Efgartigimod PH20 in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: ADHERE / ADHERE + Trial Interim Analysis

Background and Aims In ADHERE, subcutaneous efgartigimod PH20 (1000 mg once weekly) was effective and well tolerated in participants with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). ADHERE+ is an open‐label extension of ADHERE assessing long‐term safety and efficacy. Methods Eligible participants from ADHERE run‐in period (prior CIDP treatments discontinued), stage A (open‐label efgartigimod), and stage B (stage A responders randomized to placebo or efgartigimod) could roll over to ADHERE+ and receive efgartigimod. The primary outcome was to assess long‐term safety and tolerability. Efficacy outcomes evaluated adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score, Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) score, and mean grip strength (GS) from ADHERE run‐in baseline through ADHERE+ week 36. Results At interim data cut‐off (February 16, 2024), 228/229 eligible participants advanced to ADHERE+. Prolonged efgartigimod exposure did not increase the incidence ( n = 171/228 [75.0%]) or severity of TEAEs (grade ≥ 3 TEAEs, n = 41/228 [18.0%]); regardless of immunoglobulin G level, there was a low incidence of infections. Stage A responders reported long‐term clinically meaningful improvements in mean aINCAT (decreased by 1.2 points), I‐RODS centile metric (increase of 8.8 points), and GS scores (increase of 17.5 kPa) from run‐in baseline to ADHERE+ week 36, irrespective of stage B treatment. Interpretation Interim results from ADHERE+ indicate long‐term efgartigimod PH20 treatment in participants with CIDP was well tolerated (maximum exposure = 187.3 weeks; mean (SD) treatment duration = 58.0 [33.8] weeks). Clinically meaningful improvements in disability and strength were observed across assessments, regardless of stage B treatment or prior treatment status, with greater improvements seen over time.