Managing Partial Responders in Atopic Dermatitis: When to Optimize, Switch, or Combine Treatments

In this episode of Topical Conversations, G. Michael Lewitt, MD, joins David Cotter, MD, to examine a common yet underrecognized challenge in atopic dermatitis (AD) management: how to care for patients who respond to systemic therapy but fall short of full clearance. The discussion focuses on identifying partial responders, optimizing ongoing treatment, determining when to adjust or transition therapies, and navigating conversations about realistic expectations and long-term disease control.

Rethinking AD as a systemic disease

Drs Lewitt and Cotter open the discussion by addressing a foundational challenge in AD care: helping patients understand that it’s not simply a “skin problem,” but a systemic inflammatory disease with diverse clinical expressions.  

He notes that conversations about systemics flow naturally from an assessment of severity, treatment goals, and disease impact. Patients often voice concerns about “immunosuppression,” and Dr Lewitt suggests reframing this as “immunomodulation” instead, helping patients understand mechanism, safety, and expected outcomes. He also stresses that severity assessment should not rely exclusively on Eczema Area and Severity Index scores or body surface area (BSA) affected; high-impact areas and patient-perceived burden often tip the scale toward systemic therapy.

The role of topicals in a systemic era

Although systemic therapy is appropriate for many patients, Dr Cotter emphasizes that topical therapy remains central. Tapinarof, ruxolitinib, and other topical options can serve both as initial therapy and as “touch-up paint” during systemic treatment. He routinely checks whether partial responders have tapered or discontinued their topicals, an often-overlooked contributor to perceived loss of efficacy with systemics.

Managing partial or nonresponders

The clinicians then move into the core challenge: patients who respond incompletely or lose response over time.

Dr Cotter describes his decision-making framework for adding, subtracting, or switching therapies.  When patients improve but plateau (better itch control, reduced BSA, milder disease but persistent burden), he discusses next steps. Options include cycling biologics, switching classes, or transitioning to a small molecule. He highlights available evidence, particularly a head-to-head trial showing that patients with inadequate response to dupilumab were more likely to improve when switched to upadacitinib.

Another strategy involves using a JAK inhibitor as a short-term “fire extinguisher” for severe flares or rapid symptom control, followed by a transition back to a biologic for long-term maintenance, a preferred option over prednisone in his practice.

When patients want to stop systemic therapy

A common scenario is the patient who feels markedly better and asks whether treatment can be discontinued. Dr Cotter frames this as “forever for now,” emphasizing patient autonomy while counseling on likely outcomes.

He discusses differences by class:

• JAK inhibitors typically show loss of benefit within days of discontinuation
• Some biologics (lebrikizumab, dupilumab, tralokinumab) may allow a significant proportion of responders to maintain stable disease for up to a year off therapy

Before stopping outright, he often also negotiates dose interval extension (eg, dupilumab every 3 weeks instead of every 2; tralokinumab every 4 weeks instead of every 2; lebrikizumab every 4 weeks or even every 8 weeks in selected responders instead of every 2) with his patients.

Closing thoughts

Dr Cotter closes by highlighting the advantage of today’s toolkit: the flexibility to mix and match systemic and nonsteroidal topical therapies. This allows clinicians to tailor care, maintain long-term control, and address breakthrough disease with precision and safety.

Key takeaways

• AD must be framed as a systemic inflammatory disease to guide patient acceptance of systemic therapy
• Disease severity assessment should incorporate quality of life, high-impact areas, and patient-reported burden, not just EASI or BSA
• Topicals remain essential for priming treatment, supporting systemics, and managing breakthrough disease
• For partial responders, evaluate adherence to topicals before modifying systemic therapy
• Switching options include biologic-to-biologic transitions, class switching, or moving to small molecules; existing head-to-head data can help guide choices
• JAK inhibitors can serve as short-term rescue agents before returning to biologics for long-term maintenance
• When patients want to stop therapy, consider interval extension before discontinuation and counsel on expected durability of response by therapeutic class
• Combining systemics with modern, nonsteroidal topicals allows individualized, long-term disease control