Meta-Analysis Finds Upadacitinib to Be Most Effective for AD-Related Pruritus

Image Credit: © lial88 - stock.adobe.com

A recent network meta-analysis compared several approved and potential targeted monotherapies in treating AD-associated pruritus among adults and teens.¹ Although other treatments demonstrated promising antipruritic effects, 30 mg of upadacitinib proved to be the best available option.

Chronic pruritus is frequently reported as the most severe symptom of the disease, with over 85% of patients experiencing daily pruritus and 42% reporting itching for 18 hours or more each day.² This painful cycle can severely impact patients’ quality of life due to sleep disturbances, anxiety, depression, and other health impairments.

Researchers extracted data from phase 3 and 4 randomized controlled trials published from February 3, 2023, to August 24, 2024. These studies were found through PubMed, Embase, and Cochrane Library online databases. Investigators used a combination of search terms related to ‘atopic dermatitis’ and ‘randomized controlled trial.’

After the screening, exclusion, and extraction processes, 16 studies were selected. The included 8,462 participants were all 12 years of age and older and were clinically diagnosed with moderate to severe AD. Reviewers also assessed the risk of bias and found evidence of a high risk of bias in 2 articles, a possible risk in 4 articles, and a low risk in 5 articles.

In terms of further selection criteria, the outcome measure was the proportion of patients achieving a ≥ 4-point improvement from baseline on the Pruritus Numerical Rating Scale (NRS). Primary endpoints were based on patients achieving this improvement at week 12 or 16 while secondary endpoints were evaluated for the same improvement at weeks 2, 4, and 8. 

Combination therapies such as concomitant topical corticosteroids, topical calcineurin inhibitors, antihistamines, and traditional immunosuppressants were excluded from this particular study. The following targeted treatments and their dosage groups were included in the analysis:

• Abrocitinib at 100 mg and/or 200 mg daily
• Baricitinib 2 mg and/or 4 mg daily
• Dupilumab 300 mg administered every 2 weeks
• Lebrikizumab 250 mg administered every 2 weeks
• Stapokibart 300 mg administered every 2 weeks
• Tralokinumab 300 mg administered every 2 weeks
• Upadacitinib at 15 mg and/or 30 mg daily

All therapies had better outcomes over placebos but 30 mg of upadacitinib showed the highest response rate and was statistically more effective than all other treatments at weeks 2, 4, 8, 12, and 16. Following that, the next most effective treatments were abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg. This was observed in both the primary and secondary outcome measures.

In week 2, the highest response rates were found in upadacitinib 30 mg, followed by baricitinib 4 mg, abrocitinib 200 mg, upadacitinib 15 mg, and lebrikizumab 250 mg. Dupilumab 300 mg ranked much lower compared to its counterparts. By week 4, upadacitinib 30 mg continued to show great improvement, followed by upadacitinib 15 mg, baricitinib 4 mg, and abrocitinib 200 mg. Continued poor responses were shown in lebrikizumab 250 mg and dupilumab 300 mg, especially at weeks 4 and 8.

Investigators did note some limitations such as the focus on only phase 3 trials and the lack of inclusion for all dosage groups of these systemic therapies. Further head-to-head randomized control trials with an enriched data pool are recommended to directly compare the regimens and confirm these clinical findings.

“Nevertheless, the findings retain clinical significance. Future research should prioritize well-designed clinical studies centered on itch in atopic dermatitis to enrich the data pool,” the authors wrote. “We will continue to monitor research developments and refine the meta-analysis to provide high-quality evidence for clinical practice.”

References

1. Xiong M, Gao Q, Ren H, Zhong T. Comparative efficacy of targeted systemic therapies for pruritus in moderate-to-severe atopic dermatitis without topical treatment: a network meta-analysis. J Dermatolog Treat. 2024;35(1):2432930. doi:10.1080/09546634.2024.2432930

2. AAAAI/ACAAI JTF Atopic Dermatitis Guideline Panel, Chu DK, Schneider L, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations. Ann Allergy Asthma Immunol. 2024;132(3):274-312. doi:10.1016/j.anai.2023.11.009