Overcoming Barriers to Systemic Therapy in Atopic Dermatitis

In this episode of Topical Conversations, Brad Glick, MD, and James Del Rosso, DO, discuss the delayed initiation of systemic treatments, particularly injectables for atopic dermatitis (AD). They explore the barriers both patients and providers face when considering advanced therapy, how to navigate conversations with patients, and where emerging biologics like lebrikizumab fit into the treatment landscape. 

Shifting the conversation: helping patients understand systemic therapy 

Many patients hesitate when the topic of systemic therapy is introduced, sometimes assuming that topicals alone should be sufficient. Dr Glick compares this to the early days of biologic therapy for psoriasis, noting that AD is not just a surface-level condition but rather one driven by internal inflammatory pathways. 

When discussing treatment escalation with patients, he focuses on educating them about cytokines, explaining that they drive inflammation and itch, which topical treatments cannot fully address. He also reinforces the need for systemic intervention to patients by explaining that AD is often associated with systemic comorbidities, such as asthma, anxiety, depression, and sleep disturbances. 

Why are so many dermatologists still hesitant? 

Dr Glick notes that it’s not just patients who hesitate when it comes to systemic treatments, estimating that only 30% of dermatologists routinely prescribe systemic biologics for AD, raising the question: what’s holding back the other 70%? 

He emphasizes that while biologic options like lebrikizumab (an IL-13 inhibitor) and dupilumab (an IL-4/IL-13 inhibitor) have excellent safety profiles, JAK inhibitors may have contributed to overall hesitation around systemic treatments among some providers. 

Addressing topicals, Dr Del Rosso reiterates that they have a place in treatment but cannot address the root cause of AD in many patients. He notes that his threshold for initiating systemic therapy has become lower, given that patients with AD often experience significant itch and sleep disruption. 

Drs Glick and Del Rosso compare AD to psoriasis and acne, questioning why it has been standard practice to wait until disease worsens before initiating advanced therapies. With new insights into the Th2 inflammatory pathways, they stress the need to proactively treat AD earlier with systemic therapies rather than relying on reactive treatment strategies. 

Lebrikizumab: a unique addition to the ad treatment landscape? 

With IL-13 inhibition recognized as a key target in AD, Dr Del Rosso asks whether lebrikizumab offers anything new or if it’s just another “me too” biologic. 

Dr Glick highlights its distinct mechanism of action, explaining that while dupilumab blocks IL-4 and IL-13 via dual receptor inhibition, lebrikizumab selectively inhibits IL-13 by targeting the IL-13 alpha receptor, making it a particularly targeted therapy for AD. 

Dr Del Rosso also points to long-term data showing that some patients maintain response even after stopping lebrikizumab, noting that this could offer more flexibility for patients who need to pause treatment due to insurance changes or travel without experiencing an immediate relapse. They compare this to oral systemic medications, which require daily dosing and can lead to quick relapse if stopped. 

Addressing patient fears and misconceptions 

Despite the strong safety profiles of modern biologics, Dr Glick acknowledges that patients still express fears about systemic treatments, often influenced by direct-to-consumer advertising for older psoriasis biologics with warnings about severe adverse events. 

He advises his colleagues to differentiate AD biologics from older psoriasis therapies in discussions with patients and reassure them that IL-4, IL-13, and IL-31 inhibitors have well-characterized, predictable safety profiles. 

Key takeaways 

• Systemic therapy is often delayed in AD, despite evidence that earlier intervention can improve outcomes and prevent progression 
• Patient education is crucial; dermatologists should aim to help them understand that AD is driven by internal inflammation that topicals may not address 
• More dermatologists need to embrace systemic therapy, as current prescribing rates remain low despite the strong safety profiles of modern biologics 
• Lebrikizumab offers a unique approach to IL-13 inhibition, showing significant itch reduction and sustained efficacy even after treatment discontinuation 
• Patient fears about systemic therapy are often based on outdated perceptions, making it essential for dermatologists to address misconceptions head-on