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Eczema (dermatitis)
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
Crisaborole is a topical PDE4 inhibitor indicated for the treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older. It can be used on the face and skinfolds but may sting when applied. It is most useful as maintenance therapy for mild to moderate eczema.
Current Recommendations for the Treatment of Psoriasis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Topical tofacitinib and topical ruxolitinib inhibit JAK, a tyrosine kinase that initiates an inflammatory signaling pathway activated by cytokines. Topical tofacitinib, which selectively inhibits JAK1 and JAK3, showed a statistically significant reduction in target plaque severity score at week 4 compared with placebo.36 Topical ruxolitinib, which selectively inhibits JAK1 and JAK2, was shown to improve lesion thickness, erythema, scaling, and area compared with placebo with good tolerability.37 Crisaborole is a boron-based molecule that inhibits PDE4, resulting in inhibition of the nuclear factor kappa-B (NF-kB) pathway and decreased pro-inflammatory cytokines. Phase II clinical trials on crisaborole have shown significant reductions in target plaque severity score compared with placebo with no treatment-related adverse events.38 Larger trials are underway to establish safety and efficacy of these small molecules.
Current and future topical treatments for psoriasis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Shivani Nanda, Linda Stein Gold
Crisaborole is a topical, boron-containing, anti-inflammatory compound that is a phosphodiesterase 4 (PDE4) inhibitor resulting in suppression of TNF-α, IL-23, IL-12, and various other downstream cytokines via an increase in intracellular cyclic adenosine monophosphate (cAMP) levels.77 It is currently under review by the FDA for the treatment of atopic dermatitis. In a randomized, double-blinded bilateral trial, 35 patients were randomized to receive either Crisaborole 5% ointment applied twice daily or vehicle. Assessment at day 28 revealed that 40% of plaques were clear or almost clear in those receiving Crisaborole versus 6% in those receiving vehicle.78 A subsequent dose-ranging study found 2% Crisaborole ointment applied twice daily to be the most effective dose with an improvement compared with vehicle.78 Furthermore, Crisaborole appears to be well tolerated with only mild to moderate application sites and initial studies suggest that it is well tolerated even in the intertriginous areas.78
Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2023
Ariana Moreno, Yael Renert-Yuval, Emma Guttman-Yassky
Crisaborole is a steroid sparing topical agent that functions as a phosphodiesterase-4 (PDE4) inhibitor. It is approved for the treatment of mild-to-moderate AD in patients two years of age and older. PDE4 is elevated in AD and plays an active role in the production of proinflammatory cytokines, including Th2-related (IL-5, IL-10), Th1-related (IFNg, TNFa) and Th17/Th22-related (IL-17, IL-22) [87,88]. Bidaily application of crisaborole resulted in improvement of AD severity as early as day eight of treatment, as well as sustained improvement in pruritis [89]. In both the pediatric and adult population, crisaborole provided early relief of pruritis as early as day six, as noted by a 1-grade NRS improvement from baseline [90]. A randomized, multicenter, double blind study analyzing 86 patients 12–17 years of age treated with either 0.05% or 2% crisaborole ointment for 29 days found that both regimens improved AD severity index (ASDI), with the 2% regimen resulting in a 72% improvement in ASDI for 62% of patients [91]. In patients 3 months to 17 years of age, crisaborole was associated with ISGA clear or almost clear by day 29 in 47.3% and 50% of pediatric patients [92].
Pharmacological management of atopic dermatitis in the elderly
Published in Expert Opinion on Pharmacotherapy, 2020
Alexander N. Howell, Rima I. Ghamrawi, Lindsay C. Strowd, Steven R. Feldman
Crisaborole was approved in 2016 in the United States for the topical treatment of mild-to-moderate AD in patients 2 years of age and older [15]. Crisaborole is a small molecule (251.1 Da) which allows for effective penetration of the skin with anti–inflammatory effects [31]. It contains a boron atom in its structure which allows it to selectively inhibit phosphodiesterase 4 (PDE4). [31,54,] PDE4 is a pro-inflammatory molecule and the most prevalent PDE present in keratinocytes and immune cells [55,56,]. Inhibition of PDE4 in these cells leads to increased intracellular cyclic adenosine monophosphate (cAMP), leading to activation of protein kinase A and inhibition of many pro-inflammatory pathways that include nuclear factor kappa beta and NFAT [57]. Crisaborole reduces levels of IL-2, IL-3, IL-5, IL-13, IL-31, interferon-gamma, and tumor necrosis factor-alpha [31,55,57,,].
Utility of boron in dermatology
Published in Journal of Dermatological Treatment, 2020
David G. Jackson, Leah A. Cardwell, Elias Oussedik, Steven R. Feldman
Crisaborole reduced the severity of atopic dermatitis lesions by a range of 54% to 71% when compared to control groups (11). (Table 1) Crisaborole has a dose-dependent effect on atopic dermatitis as crisaborole 2% ointment was more efficacious than crisaborole 0.5% ointment and twice-daily dosing was more efficacious than once-daily dosing (11). Crisaborole 2% ointment administered twice-daily was the most effective crisaborole regimen for atopic dermatitis. Age, race and gender did not influence its efficacy (24,25). Patients treated with crisaborole ointment typically had marked reduction in rash severity and pruritus (21,23). In one study, over 50% of patients reported near total or total clearance of lesions (21). The adverse effects of topical crisaborole were typically mild, including pain, pruritus and erythema at the application site (21–24). Crisaborole ointment was well-tolerated, even when applied to sensitive areas such as the face, genitals, and intertriginous areas of healthy volunteers (22).