Biologic and Small Molecule Therapy in Atopic Dermatitis
Abstract
:1. Introduction
2. Current Therapies
3. Phosphodiesterase 4 Inhibitors
3.1. Crisaborole
3.2. Roflumilast
3.3. Difamilast
4. Overview of Biologics
4.1. Dupilumab
4.2. Tralokinumab
4.3. Lebrikizumab
4.4. Nemolizumab
4.5. Rocatinlimab
5. Overview of Small Molecules
5.1. Janus Kinase Inhibitors
5.1.1. Baricitinib
5.1.2. Upadacitinib
5.1.3. Ruxolitinib
5.1.4. Abrocitinib
6. TRPV1 Antagonist
7. Aryl Hydrocarbon Receptor Antagonist
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Therapeutic | Mechanism of Action | Efficacy Summary | Key Studies |
---|---|---|---|
Dupilumab | Inhibits IL-4 and IL-13 signaling through competitive binding to the shared subunit of the IL-4 receptor, leading to gene expression changes that normalize skin condition. | +++ (High efficacy demonstrated in numerous randomized control trials with significant improvements in IGA and EASI scores, along with patient-reported outcomes. Comparable effectiveness between dosing frequencies.) | SOLO 1 and SOLO 2 [38,39] LIBERTY AD CHRONOS Trial [40] LIBERTY AD ADOL Trial [41] |
Tralokinumab | Targets and binds strongly to IL-13, inhibiting the inflammatory processes associated with AD. | ++ (Improvement in IGA scores and EASI-75 in phase 3 trials. Maintenance of efficacy up to week 52 demonstrated, with AEs including infections and headaches.) | ECZTRA 1 [46] ECZTRA 2 [46] ECZTRA 6 [47] |
Lebrikizumab | Directly targets IL-13, interrupting the signaling pathway responsible for inflammation and potentially restoring the skin’s natural barrier function. | +++ (Significant improvement in IGA scores and EASI-75 responses in trials. High efficacy in reducing pruritus and improving sleep among patients, with noted AEs such as conjunctivitis and dermatitis exacerbation.) | Advocate1 Trial [50] Advocate 2 Trial [50] |
Nemolizumab | Targets and inhibits IL-31RA, disrupting the IL-31 signaling pathway associated with the itch-scratch cycle in AD. | ++ (Significant reductions in pruritus scores and improvements in skin lesions and disease severity reported. Mild-to-moderate AEs noted, including injection site reactions and upper respiratory tract infections.) | XCIMA Trial [53] |
Rocatinlimab | Inhibits and reduces OX40 pathogenic T cells responsible for AD inflammatory responses by blocking OX40. | ++ (Significant reductions in EASI score observed in phase IIb study, with progressive and maintained improvements post-treatment. Common AEs include pyrexia, nasopharyngitis, and chills.) | [54] |
Janus Kinase Inhibitors (JAKi) | Inhibits JAK-STAT signaling pathway, crucial for the cytokine-mediated communication involved in AD. | +++ (Significant improvement in AD symptoms and disease measures in clinical trials, highlighting efficacy in both pediatric and adult populations with manageable safety profiles.) | BREEZE-AD PEDS Clinical Trial [61] |
Baricitinib | BREEZE-AD4 Trial [62] | ||
Upadacitinib | The AD Up Trial [63] | ||
Ruxolitinib | The TRuE-AD Trial [64] | ||
Abroctinib | The JADE MONO 1 and JADE MONO 2 [65,66] | ||
Crisaborole | Selective inhibitor of PDE4, reducing inflammation by inhibiting the breakdown of cyclic adenosine monophosphate. | ++ (Effective in reducing AD symptoms with a good safety profile, primarily involving application site reactions. Demonstrated efficacy in both adult and pediatric patients.) | CrisADe CARE 1 [27] AD-301 Trial [28] AD-302 Trial [28] [23,26,29] |
Roflumilast | Second-generation PDE4 inhibitor, reducing inflammation with a reduced risk of causing emesis compared to predecessors. | + (Showed minimal effectiveness in AD treatment in clinical trials, with AEs including application site pain and gastrointestinal symptoms.) | [22] |
Difamilast | PDE4 inhibitor that reduces cytokine production associated with inflammatory conditions like AD. | +++ (Significant improvements in AD severity and symptoms with a well-tolerated safety profile in both adult and pediatric patients.) | [35,36] |
Asivatrep (TRPV1 Antagonist) | Inhibits TRPV1, reducing pruritus and inflammation associated with AD. | ++ (Demonstrated effectiveness in improving clinical signs and symptoms of AD with a well-tolerated safety profile.) | CAPTAIN-AD Trial [67] |
Tapinarof (Aryl Hydrocarbon Receptor Antagonist) | Modulates the aryl hydrocarbon receptor signaling pathways, reducing proinflammatory cytokine expression and oxidative stress. | ++ (Showed promising efficacy and safety in treating AD, with improvements in skin clarity and reduced inflammation in clinical trials.) | [71,72] |
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Shergill, M.; Bajwa, B.; Yilmaz, O.; Tailor, K.; Bouadi, N.; Mukovozov, I. Biologic and Small Molecule Therapy in Atopic Dermatitis. Biomedicines 2024, 12, 1841. https://doi.org/10.3390/biomedicines12081841
Shergill M, Bajwa B, Yilmaz O, Tailor K, Bouadi N, Mukovozov I. Biologic and Small Molecule Therapy in Atopic Dermatitis. Biomedicines. 2024; 12(8):1841. https://doi.org/10.3390/biomedicines12081841
Chicago/Turabian StyleShergill, Mahek, Barinder Bajwa, Orhan Yilmaz, Karishma Tailor, Naila Bouadi, and Ilya Mukovozov. 2024. "Biologic and Small Molecule Therapy in Atopic Dermatitis" Biomedicines 12, no. 8: 1841. https://doi.org/10.3390/biomedicines12081841