Insufficient Disease Control in Moderate-to-Severe AD: Year-long Longitudinal Study Reveals Treatment Gaps

Dr. Lawrence Eichenfield explained why therapeutic inertia continues to be an issue in AD treatment.

A recent study presented at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference highlighted has shed light on the persistent issue of therapeutic inertia in the treatment of moderate-to-severe atopic dermatitis (AD), even with the advent of newer, advanced systemic therapies. Over a 12-month period, many patients treated with systemic therapies failed to achieve satisfactory control of their condition.

Lead author Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and a professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine, as well as a member of the Practical Dermatology^® Editorial Board, addressed this concern by emphasizing the need for a dynamic and goal-oriented approach to tackle therapeutic inertia and enhance treatment efficacy. 

“Therapeutic inertia is the delay or failure of timely adjustment to therapy when treatment goals are not met," Dr. Eichenfield told Practical Dermatology. "But treatment goals aren’t ‘set in stone,’ and are influenced by the efficacy of alternative medications, as well as the perception of risks associated with the medications individuals are on and other agents they may consider as alternatives.”

The current study aimed to evaluate the occurrence of therapeutic inertia, focusing on patients whose condition did not respond adequately to the initial systemic therapy, be it Advanced Systemic Therapy (AST) like upadacitinib or dupilumab, or Conventional Systemic Therapy (CST) like methotrexate or systemic corticosteroids.

Consequently, the researchers conducted a longitudinal analysis of 3,457 patients from 39 centers in the US and Canada diagnosed with moderate to severe AD. To be eligible, patients had to have a validated Investigator’s Global Assessment of AD (vIGA-AD) score of 3 or 4 within 45 days before starting the systemic treatment or within 14 days after the treatment began.

“The study was based on establishing optimal response (was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤ 2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution), vs. inadequate response and looking at delayed or failure to escalate treatment in patients not achieving adequate disease control (defined as “therapeutic inertia”),” Dr. Eichenfield explained. Patients who had previously undergone either advanced or conventional systemic therapy for AD before the set index date were excluded from the study.

Among the 2,107 patients diagnosed with moderate to severe AD, 445 met the study criteria. These patients were predominantly adults (63.8%), female (62.0%), and identified as Non-Hispanic White (45.4%), with an average age of 31 years. The majority (92%) commenced treatment with AST, with dupilumab being the most frequently used systemic therapy (86.5%). The mean vIGA-AD score at the beginning of AST treatment was 3.3, while for CST, it was 3.6 (P<0.01). The average baseline itch score was 7.6.

During the follow-up period, the most commonly used AST for patients with atopic dermatitis was dupilumab. Out of 395 AST patients, 36.7% also utilized concurrent topical corticosteroids or topical calcineurin inhibitors. Despite receiving either AST or CST for up to 12 months, a notable proportion of patients faced challenges with their treatment responses.

Regarding inadequate responses in achieving moderate targets, at the 6-month mark, approximately 37% and nearly 67% of AST-treated patients experienced insufficient skin clearance and itch relief, respectively. By the 12-month milestone, these figures improved to around 30% and 66%, respectively. Similar patterns were observed among CST-treated patients.

In terms of not achieving optimal targets, 82% and 79% of AST-treated patients did not reach satisfactory skin clearance and itch relief, respectively, at 6 months. These percentages slightly increased to approximately 85% and 88%, respectively, by the end of 12 months. Comparable trends were seen in CST-treated patients.

“This suggests that adding topical calcineurin inhibitors or corticosteroids may not provide what I would call ‘significant enough’ benefits and may contribute to therapeutic inertia," Dr. Eichenfield noted.

Additionally, the study highlighted that patients starting AST treatment after September 21, 2021, when new AST options (tralokinumab, upadacitinib, and abrocitinib) were introduced, had similar rates of inadequate responses over the 12-month period compared to the overall AST cohort.

“Currently, a post hoc analysis is underway to delve deeper into how baseline characteristics affect treatment outcomes," added Dr. Eichenfield. "This analysis aims to provide a clearer understanding of the impact of these characteristics on therapeutic inertia and persistent inadequate response to treatment."

Dr. Eichenfield also further highlighted the importance of redefining treatment objectives.

“Aiming for higher measures of efficacy is important. Regular, thorough assessments and documentation of outcomes (such as itch response and skin clearance) are important to evaluate progress against these goals. When these objectives are not met within a specified timeframe (3-6 months) indicating inadequate response, clinicians should be prepared to adjust the treatment strategy. This might include switching to more potent or novel therapeutic options that align better with the patient’s condition.”

In addition to medical adjustments, Dr. Eichenfield stressed the significance of patient education and engagement throughout the treatment journey.

 “Emphasizing patient education and engagement in this process is vital to ensure understanding, encourage appropriate shared decision making, and promote adherence to the treatment regimen," he said. "Such an approach not only addresses the physical symptoms of atopic dermatitis but also considers the psychological and quality-of-life impacts, thereby fostering a more holistic and effective management of the disease.”