Interpreting the ADHERE and ADHERE+ Post Hoc Analysis

While primary end points often determine whether a clinical trial meets its objectives, secondary and post hoc analyses frequently provide the clinical context that physicians need to apply those findings in practice. For chronic inflammatory demyelinating polyneuropathy, understanding how disability changes over time may be just as important as knowing whether relapse is prevented.

In this NeurologyLive® Special Report, Karissa Gable, MD, FAAN, professor of neurology at Duke University, and Jeffrey Allen, MD, associate professor of neurology at the University of Minnesota, examine a post hoc analysis from the ADHERE and ADHERE+ studies presented at the 2026 Peripheral Nerve Society Annual Meeting. Their discussion explores how additional analyses of subcutaneous efgartigimod PH20 (Vyvgart Hytrulo) can help clinicians better interpret long-term functional outcomes in patients with CIDP.

This episode focuses on why the post hoc analysis was conducted and what it adds beyond the original study findings. Gable and Allen review changes in INCAT scores throughout the different phases of ADHERE, discuss the durability of treatment response over time, and explain why sustained reductions in disability may represent an important benchmark when evaluating treatment success.

Jeffrey Allen, MD:

The primary outcome measure in the ADHERE trial was relapse based on changes in the INCAT score during the randomized Stage B portion of the study, comparing patients who remained on treatment with those who discontinued treatment.

After that randomized placebo-controlled phase, patients were allowed to enter an open label extension and were followed for an additional 36 weeks. Throughout the study, including before enrollment, during the open label Stage A, the randomized Stage B, and the open label extension, INCAT scores were collected at each stage.

What we observed was that INCAT scores improved during the open label Stage A while all patients were receiving efgartigimod. During Stage B, patients who were randomized to placebo lost some of that improvement, whereas those who remained on efgartigimod maintained their gains. Once everyone entered the open label extension and resumed efgartigimod, patients who had previously received placebo improved to a level similar to those who had remained on active treatment throughout the study. Patients who stayed on efgartigimod continued to maintain those improvements over time.

Looking at the entire study population, from the time patients entered the trial while receiving their background therapy through the end of the extension study, the overall improvement in INCAT score was approximately 1.2 points. That demonstrates a clinically meaningful improvement among patients who initially responded to efgartigimod during Stage A. It's important not to overinterpret these findings as a direct comparison with background therapies because there are details we don't know about those treatments. However, the analysis gives us confidence that patients have the capacity to continue improving over as long as 36 weeks. It also tells us something important about durability, namely that patients who respond tend to maintain that response over time.

Karissa Gable, MD, FAAN:

Exactly. As the weeks progressed, the proportion of responders who either maintained their response or achieved an INCAT score of 1 or lower continued to increase over time. Ultimately, about one-third of Stage A responders reached an INCAT score of 1 or less at some point during the study.

The investigators also looked at durability. Among the 77 of 196 patients who maintained a response across at least two consecutive visits, 80.5% achieved an INCAT score of 1 or less. Looking at patients who maintained that response across three or more consecutive visits, 70.1% of those 77 patients still had an INCAT score of 1 or less after 24 weeks. Those findings reinforce the durability of the treatment response over time.