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Use of a topical PDE4 inhibitor in an adult patient with moderate atopic dermatitis

Dr. Ka-Keung Ho
Specialist in Dermatology & Venereology
Private practice
Hong Kong
09 Apr 2021

History and presentation

The patient is a 22-year-old man with a long history of atopic dermatitis (AD). He first consulted a doctor for AD at 5 years of age. At the time, the patient’s AD was mild, manifesting as occasional skin flare-ups on the face, knees and arms. During his childhood, these symptoms were mainly triggered by seasonal changes in weather.

After the patient began attending university, however, the stress of student life and examinations began to trigger more frequent flare-ups, with his AD severity becoming moderate. In the final year of university, before his final examinations, the patient’s AD had become moderate with skin rashes forming all over his body, affecting 20 percent of total body surface area.

Treatment and response

In his childhood years, the patient’s mild AD was generally well controlled by the application of emollients to the affected areas. For severe breakouts, mild topical corticosteroid (TCS) was also occasionally used.

With the worsening of AD symptoms during his final year of university, the patient was prescribed oral prednisolone of about 30 mg per day, which he took for 6 weeks. Although he responded well to treatment, he was not able to taper off prednisolone without reappearance of symptoms. To avoid long-term oral steroid use, he was prescribed the immunosuppressant ciclosporin at 100 mg twice per day and a topical calcineurin inhibitor (tacrolimus 0.1 percent ointment) to be applied twice per day. However, after 2 months, the patient developed hypertension (140/90 mm Hg) and deranged renal function with elevated serum creatinine levels (>110 µmol/L).

The patient presented to our clinic and, in order to avoid long-term side effects of ciclosporin, was gradually taken off it. In view of his prior experience with TCS and immunosuppressive agents, he was switched to crisaborole ointment (2 percent). The patient began to respond to crisaborole within 2 weeks of treatment, showing improvements of AD symptoms with reduced skin redness and itchiness. (Figure) He was also given oral antihistamines to further relieve itchiness. After 1 month of crisaborole treatment, his symptoms showed substantial improvements, with affected body surface area reducing to approximately 5 percent.

The patient has since been taken off antihistamines and no longer requires any oral medication to supplement crisaborole treatment. Currently in total remission, he has reported no significant side effects and continues using crisaborole over the body and on his face.  

Discussion

According to current guidelines of the American Academy of Dermatology, topical application of emollients and moisturizers should be the primary treatment for mild cases of AD. Even in moderate to severe forms of the dis-ease, moisturizers should be used in conjunction with recommended pharmacological treatments (such as TCS or TCI) as an important component of maintenance therapy aimed at pre-venting flare-ups.1

As our patient’s AD became more severe during a stressful period in his life, he was prescribed oral prednisolone for better disease control. However, use of systemic corticosteroids is associated with potential adverse events (AEs), such as elevated blood pressure, increased risk of diabetes, and liver function impairment.2 Similarly, prolonged use of ciclosporin is as-sociated with a number of side effects, including nephrotoxicity and  hyper-tension, and should be avoided.3

Crisaborole is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor that has been approved by the US FDA since 2016 as a topical treatment of mild-to-moderate AD.4 Crisaborole is available in Hong Kong for topical treatment of mild-to- moderate AD in patient ≥2 years  of age.5,6

Several clinical trials have investigated crisaborole’s efficacy and safety in patients with mild-to- moderate AD. In two identically  designed multicentre, vehicle- controlled, double-blind phase III studies (AD-301 [n=759] and AD-302 [n=763]), patients with AD were randomized to receive crisaborole or vehicle treatment, applied to skin  lesions twice daily for the 28-day study period.6,7

Results showed that a higher percentage of crisaborole-treated patients achieved an Investigator’s Static Global Assessment (ISGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement at day 29 vs vehicle-treated patients (AD- 301: 32.8 percent vs 25.4 percent; p=0.038) (AD-302: 31.4 percent vs 18.0 percent; p<0.001). Patients treated with crisaborole also achieved ISGA score of 0 or 1 earlier (p<0.001) and benefited from greater reductions in disease severity than those who received vehicle treatment (AD-301 and AD-302 pooled data: erythema, excoriation, lichenification, p<0.001 for all; exudation, p=0.001;induration/papulation, p=0.002).7 A higher percentage of crisaborole-treated patients experienced an improvement in pruritus earlier (pooled data: 1.37 days vs 1.70 days; p=0.001) and throughout the duration of the two studies (pooled data, days 8, 15 and 22: p<0.001; day 29: p=0.002). Crisaborole was well tolerated with treatment-emergent AEs comparable to the vehicle group.7

HK-PFI-718md_01

Unlike corticosteroids, long-term use of topical crisaborole showed few safety concerns. In a 48-week, single-arm, follow-up extension study (AD-303) that assessed the long-term safety results of AD patients who continued crisaborole treatment after completing the phase III AD-301 and AD-302 studies, prolonged treatment with crisaborole was associated with low occurrence of treatment-emergent and treatment-related AEs.8 There was also no evidence of application-site cutaneous adverse reactions, such as skin atrophy, a side effect associated with prolonged use of TCS, especially  in sensitive areas, such as the face and groin.8 The absence of these  adverse reactions enabled our patient to use crisaborole on his face.

Although crisaborole can be applied to the face in most cases, due to its unique mechanism of action of modulating inflammatory cytokine production, its use should be avoided around areas with an active infection.8 Crisaborole ointment use should also be avoided in patients with known hypersensitivity to crisaborole or any component of the formulation.6

Overall, this case illustrates crisaborole as an effective therapeutic option for moderate AD, with rapid onset and a very good tolerability profile.

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