Atopic dermatitis (AD) is a chronic, inflammatory skin condition that significantly impairs quality of life, often requiring systemic biologic therapy like lebrikizumab or dupilumab when topical treatments fail. While both biologics have shown efficacy in separate trials when combined with topical corticosteroids (TCS), they have not been compared in direct head-to-head clinical trials. To address this gap, researchers employed a Matching-Adjusted Indirect Comparison (MAIC), which was considered the optimal solution because it accounts for baseline population differences—such as age, sex, and disease severity—that could otherwise bias results in standard indirect treatment comparisons.
Methods
Researchers matched individual patient data from the ADhere trial (lebrikizumab plus TCS) with aggregate data from the CHRONOS trial (dupilumab plus TCS) using a method of moments approach. Baseline characteristics, including mean EASI scores and demographics, were adjusted to align the trial populations for a placebo-anchored comparison. Efficacy endpoints up to week 16 included IGA 0/1, EASI 50/75/90, and improvements in itch and quality-of-life scales. These outcomes were quantified using odds ratios, risk ratios, and risk differences to ensure statistical robustness.
Key Findings
• Comparable week-16 efficacy: Lebrikizumab plus TCS showed similar odds to dupilumab plus TCS in achieving major clinical milestones, including EASI 75 (OR 1.14) and IGA 0/1 (OR 1.39).
• Superior early itch relief: Patients treated with lebrikizumab plus TCS had a significantly higher likelihood of achieving a 4-point improvement in the Pruritus Numerical Rating Scale (PNRS) by week 4 compared to those on dupilumab plus TCS.
• Quality-of-life improvements: Both combination therapies resulted in similar improvements in the Dermatology Life Quality Index (DLQI), indicating consistent benefits for patient well-being.
• Reliability of data: Sensitivity analyses at the study-arm level confirmed the primary results, suggesting that both treatments offer similar clinical benefits in real-world settings where TCS is used concurrently.
This study is novel as it is the first indirect comparison to utilize the robust MAIC methodology to account for population heterogeneity between these two specific combination therapy trials. By correcting for baseline imbalances that previously led to biased comparisons, it provides clinicians with a more accurate assessment of short-term treatment options. The future implications of this research suggest that while both biologics are highly effective for induction therapy, further investigation is needed into long-term maintenance and whether the off-drug durability of lebrikizumab might allow for strategic treatment interruptions.
Analogy: Comparing clinical trials without adjusting for baseline differences is like comparing the speed of two runners on different terrains; a matching-adjusted comparison ensures they are both running on the same track so their true performance can be measured fairly.
Link to the study: https://link.springer.com/article/10.1007/s13555-025-01620-x
