Dual Approach to AD: Complementary Benefits of Dupilumab and JAK Inhibitors

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Affecting 15%–20% of children and up to 10% of adults, atopic dermatitis (AD) is the most burdensome skin disorder globally.¹ Its complex pathogenesis involves skin barrier dysfunction, immune dysregulation, and microbial imbalance. Key cytokines, such as IL-4, IL-13, IL-31, and others, play a pivotal role, mediated through the JAK-STAT signaling pathway.² Despite the advent of effective therapies, such as dupilumab and Janus kinase inhibitors (JAK) inhibitors, treatment for moderatetosevere AD remains challenging. A recent study investigated the effectiveness and safety of combining dupilumab with different JAK inhibitors in real-world settings.³

“Our real-world experience suggested that the combination of dupilumab and JAK inhibitors could be a favorable option for refractory moderate to severe AD and the recommended doses of the 3 approved JAK inhibitors (baricitinib, abrocitinib, and upadacitinib) as add-on therapy were probably similar in effectiveness,” researchers behind the study wrote.

Methods

The retrospective observational study evaluated 16 patients with moderate to severe AD treated at Peking University First Hospital between September 2022 and August 2023. All participants had an inadequate response to dupilumab monotherapy after 16 weeks and were subsequently treated with dupilumab in combination with 1 of 3JAK inhibitors (baricitinib, abrocitinib, upadacitinib). Outcomes, including eczema area and severity index (EASI) scores, pruritus reduction (pp-NRS), and quality of life measures such as dermatology life quality index (DLQI/CDLQI), were assessed at baseline and at multiple time points up to 16 weeks.

Results

The study enrolled 16 patients with moderate to severe AD treated with dupilumab and 1 of 3 JAK inhibitors: baricitinib, abrocitinib, or upadacitinib. After 16 weeks, researchers stated significant improvements were observed across clinical endpoints, with 100%, 87.5%, and 37.5% of patients achieving EASI 50, EASI 75, and EASI 90 responses, respectively. Median pruritus scores (pp-NRS) dropped from 8.00 to 1.00, while quality-of-life measures, including DLQI/CDLQI and POEM, showed marked reductions (p < 0.05). Researchers saw improvement as early as week 2, with the study reporting 50% of patients achieving clinically significant pruritus reduction. Comparisons among JAK inhibitors groups revealed comparable outcomes, though researchers found upadacitinib demonstrated a slightly greater reduction in EASI scores compared to abrocitinib (p = 0.034).

The study found the combination therapy was well-tolerated, with minimal adverse events reported. One patient experienced mild ocular symptoms that resolved without intervention, and no significant laboratory abnormalities or treatment discontinuations occurred. These findings highlight the effectiveness and safety of combining dupilumab with JAK inhibitors for refractory AD, with rapid and sustained improvements in disease severity and quality of life. Researchers stated further research is needed to assess long-term safety and cost implications.

Discussion

The study found the combination of dupilumab and JAK inhibitors appears to be a promising approach for refractory AD. Researchers stated each therapy targets distinct mechanism; dupilumab inhibits IL-4Rα, while JAK inhibitors interrupts broader inflammatory pathways, potentially offering complementary benefits. Despite these encouraging results, the study's limitations, including its small sample size and short duration, highlight the need for larger, longer-term investigations.

Conclusion

Researchers found concomitant therapy with dupilumab and JAK inhibitors may provide effective and safe short-term treatment for refractory moderate to severe AD. However, the high cost and absence of long-term safety data necessitate cautious use, emphasizing shared decision-making with patients and routine monitoring. The study stated future research should focus on predictors of effectiveness and the comparative benefits of JAK inhibitors monotherapy versus combination therapy.

References

1. Laughter MR, Maymone MBC, Mashayekhi S, et al. The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017. Br J Dermatol. 2021;184(2):304-309. doi:10.1111/bjd.19580
2. Ständer S. Atopic dermatitis. N Engl J Med. 2021;384(12):1136-1143. doi:10.1056/NEJMra2023911
3. Song X, Liu B, Peng C, et al. Dupilumab in combination with JAK inhibitor for refractory moderate-to-severe atopic dermatitis. Dermatologic therapy. 2024.doi:10.1155/dth/9515524