Therapeutic Inertia in Atopic Dermatitis Persists, Impacts Patient Outcomes

Brenda Simpson, MD

Credit: El Paso Dermatology

A recent study showed a significant portion of patients with moderate-to-severe atopic dermatitis fail to achieve adequate itch and disease severity targets with systemic therapies over 12 months.¹ The results indicate a substantial presence of therapeutic inertia.

Treatment responses are considered inadequate when the targets are not achieved within 3 to 6 months, according to the AHEAD treat-to-target recommendation. The delay or reluctance to modify treatment despite the treatment not meeting its goals is referred to as therapeutic inertia.

In atopic dermatitis specifically, therapeutic inertia results in prologued inadequate disease control which negatively affects patient-reported outcomes such as quality of life and sleep. Therapeutic inertia in atopic dermatitis can also potentially lead to a reliance on concomitant topical treatment. Those who do not respond well to therapies may have poor compliance or incorrect medication use, lack of access to appropriate medications, hypersensitivity to topical treatments, skin infections, and other exacerbating environmental triggers.²

Investigators sought to assess the impact of therapeutic inertia on patient-reported outcomes in individuals with moderate-to-severe atopic dermatitis undergoing systematic treatment over 3 to 12 months.¹ The observational, longitudinal study TARGET-DERM AD, led by Brenda Simpson, MD, from El Paso Dermatology, was presented at the 2024 Fall Clinical Dermatology Conference from October 24 to 27, 2024 in Las Vegas.

The team compared the proportions of patients not achieving moderate or optimal patient-reported outcome targets on patients with atopic dermatitis treated with their systematic therapy advanced (abrocitinib, dupilumab, tralokinumab, or upadacitinib) or conventional (Methotrexate, cyclosporine, mycophenolate, mofetil, azathioprine, systemic corticosteroids, and/or phototherapy). The sample included 445 participants across 39 academic and community centers in the United States and Canada with no age restriction.

Participants had to have a validated Investigators Global Assessment of atopic dermatitis (vIGA-AD) score of 3 or 4 within 45 days before starting systematic therapy or up to 14 days after. Patients also needed to have ≥ 1 vIGA-AD assessment 3 – 12 months after starting systematic therapy. Participants were excluded if they received advanced or conventional systematic atopic dermatitis therapy before the index date.

The sample had a mean age of 30.8 years and 62% were female. Participants were predominantly White (45.4%), followed by Hispanic/Latino (19.8%), Asian (14.2%), and Black (12.4%).

The study outcomes included skin or atopic dermatitis, measured with an Investigators Global Assessment of atopic dermatitis (IGA) and patient-oriented SCORing of Atopic Dermatitis (PO-SCORAD), itch measured with Patient-Reported Outcome Measurement Information System (PROMIS) Itch-Severity question evaluating Worst-Itch, eczema measured with patient-oriented eczema measure (POEM), and sleep disturbance and skin pain both measured with the Numeric Rating Scale (NRS).

Moderate targets included:

• Skin: IGA ≤ 2 improvement and 50% BSA improvement
• Itch: WI-NRS ≥ 4-point improvement (reduction)
• POEM: ≥ 4-point reduction
• PO-SCORAD: ≤ 24
• Sleep disturbance: Sleep-NRS ≥ 3-point reduction
• Skin pain: Pain-NRS ≥ 3-point reduction

As for optimal targets, they were the following:

• Skin: IGA 0/1 and BSA ≤ 2%
• Itch: 0/1
• POEM: ≤ 2
• PO-SCORAD: ≤ 10
• Sleep disturbance: ≤ 1
• Skin pain: ≤ 1

At baseline, participants had a mean IGA of 3.3 and a mean Worst-Itch of 7.6. The sample also had mean scores of 15.1 for POEM, 38.5 for PO-SCORAD, 3.3 for NRS-Pain, 4.3 for NRS-Sleep, 9.6 for Dermatology Life Quality Index (DLQI), and 10.7 for Children’s Dermatology Life Quality Index (CDLQI). Most (76.2%) had PROMIS Itch-Mood and Sleep within normal limits, but some had mild (14.9%) and moderate (8.8%) scores.

In the analysis, the team assessed the frequency and proportion of patients not achieving moderate or optimal targets at months 3, 6, and 12 following systematic therapy. They also conducted Kruskal-Wallis and Wilcoxon statistical tests to compare the groups.

Only 3 months after starting systematic therapy, majority did not achieve moderate targets for atopic dermatitis (78.9%), quality of life (79.6%), sleep (71.2%), and skin pain (81.4%). By 12 months, many still did not achieve moderate targets for atopic dermatitis (66.7%), quality of life (100%), sleep (63.8%), and skin pain (77%).

As for the proportion of patients not achieving optimal targets, the majority did not for atopic dermatitis (87.3%), quality of life (56%), and sleep (54.3%). 12 months after starting systematic therapy, the proportion of participants not achieving optimal targets for atopic dermatitis, quality of life, and sleep was 87.3%, 64.2%, and 47.2%, respectively.

“As [patient-reported outcomes] are of increasing importance, these findings suggest a need for more proactive management strategies in [atopic dermatitis] treatment,” investigators concluded.

References

1. ^{Simpson, B, Grada, A, Knapp, K, et al. Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry. Presented at 2024 Fall Clinical Dermatology Conference from October 24 to 27, 2024 in Las Vegas.}
2. ^{Johnson BB, Franco AI, Beck LA, Prezzano JC. Treatment-resistant atopic dermatitis: challenges and solutions. Clin Cosmet Investig Dermatol. 2019 Mar 21;12:181-192. doi: 10.2147/CCID.S163814. Erratum in: Clin Cosmet Investig Dermatol. 2019 Dec 19;12:931. doi: 10.2147/CCID.S241314. PMID: 30962700; PMCID: PMC6432884.}