Dr April Armstrong on The Evolving Role of PDE-4 Inhibitors

On the first day of Dermatology Week, April W. Armstrong, MD, MPH, presented on the evolving role of PDE-4 inhibitors in treating psoriasis, atopic dermatitis (AD), and seborrheic dermatitis (SD).

In her presentation, Dr Armstrong addressed limitations of current standards of care and unmet needs in disease management in addition to reviewing current clinical trial data for available and emerging topical PDE-4 inhibitors. This included how to implement strategies to increase patient adherence to these treatments.

She opened with psoriasis, focusing on trials regarding crisaborole 2% ointment and roflumilast 0.3% cream in comparison to vehicles. One trial utilized crisaborole as off-label due to only being approved for AD, and while in the trial the response at week 4 for the crisaborole group showed that about 60% of patients had improved from baseline in regard to disease severity. But when compared with roflumilast, it was less potent. In a large phase 3 trial, roflumilast demonstrated superior efficacy in disease improvement compared with vehicle, in addition to a great rapid itch response while also showcasing similar safety and tolerability to vehicle.

From this, Dr Armstrong noted that “what we can gather from tolerability data—how well this is tolerated—is important because this also is correlated with how well the patient and how long the patient will stay on medication.”

On AD, Dr Armstrong noted that crisaborole 2% ointment is approved for patients aged 3 months or older with mild to moderate disease. However, while in recent trials crisaborole 2% demonstrated strong efficacy by surpassing the vehicle, its safety and tolerability demonstrated an increase in adverse events (AEs) compared with placebo.

“In the minority of my patients who experience application site burning or stinging with crisaborole, sometimes what I do is that I’d advise them when an area is very active—when their [AD] is very active—treat those areas with topical steroids first in order to calm that area down a bit and then transition to crisaborole,” stated Dr Armstrong.

In comparison, roflumilast was utilized in a phase 2 study where it demonstrated a greater improvement in severity compared to vehicle, but with a safety and tolerability similar to vehicle; this included low rates of application site AEs. Additionally, Dr Armstrong noted that  Lotamilast, which was tested in a Japanese clinical trial for adult patients with AD, also showed some promise as a treatment.

For SD, a 8-week phase 2 study investigated roflumilast foam 0.3% as a treatment. The results of the trial demonstrated significant and rapid improvement in SD, redness, scaling, and itch. Again, rates of AEs are low with roflumilast and vehicle demonstrating similar lack of evidence of irritation in both sets of patients.

Dr Armstrong concluded her presentation by reflecting on poor medication adherence to topical agents as literature has shown these are worse than oral and when adhering to chronic dermatologic diseases. She finished by stating that the steps for improving adherence to topical treatment includes:

• choosing the right vehicle
• patient education
• follow-up visits or calls
• patient participation in treatment decisions
• positive patient/physician relationships

Reference
Armstrong A. Addressing unmet needs in the management of psoriasis, atopic dermatitis, and seborrheic dermatitis: the evolving role of PDE-4 inhibitors. Presented at: Dermatology Week 2021; September 16-19, 2021; virtual.