Oral roflumilast as a therapeutic option for psoriasis, what role does it have? Case report and literature review

Dear Editor,

Roflumilast is a selective phosphodiesterase-4 (PDE-4) inhibitor approved for the treatment of chronic obstructive pulmonary disease (COPD) (1), which may have a therapeutic role for diverse dermatologic conditions.

A 49-year-old man with no previous medical history other than obesity, was referred to the dermatology outpatient clinic for a 6-month history of skin lesions. Examination revealed erythematous and scaly plaques predominantly on the scalp and face, with particular involvement of the interciliary region, as well as the trunk and extremities. The latter were not pruritic, and the patient denied any systemic symptoms. Fungal culture was negative, and a clinical diagnosis of psoriasis was made. The total affected body surface area was 14%, while the Psoriasis Area and Severity Index (PASI) was 12.2, and the Physician’s Global Assessment (PGA) was 3 (moderate). Daily treatment was started with clobetasol foam (0.05%) on the scalp, fluticasone cream (0.05%) on the face, and betamethasone salicylic dipropionate ointment (0.05% + 2%) on the body. Blood tests revealed no relevant findings except for positive Interferon-Gamma Release Assays (IGRAs) for Mycobacterium tuberculosis (TBC). Active TBC was ruled out, and the patient refused treatment for latent TBC infection at that time.

After one month, no improvement was observed (Figure 1(A–D)), so systemic alternatives were suggested. Given the profile of the patient (obesity) and lack of access to apremilast, interleukin-17 or interleukin-23 inhibitors (which are not accepted in our hospital in without prior systemic treatment), oral roflumilast 500 μg per day was started after obtaining written consent and explaining possible side effects. After two months of treatment, the psoriatic plaques had completely cleared except for post-inflammatory hyperpigmentation, and no new lesions were observed on examination (Figure 2(A–D)). Total affected body surface area and PASI were both 0. The patient wished to discontinue treatment due to clinical improvement. He also reported weight loss of up to 5 kg (albeit coincided with stressful life events), but did not experience nausea or vomiting while taking the medication. The patient was referred to the infectious diseases department for latent tuberculosis management.

Figure 1. (A–D) Clinical presentation of the cutaneous lesions before initiating oral roflumilast. Scalp is especially affected, associated with moderate pruritus (consent from the patient was obtained).

Figure 2. (A–D) No lesions are observed after 8 weeks of oral roflumilast (consent from the patient was obtained).

Discussion

Oral roflumilast, a selective phosphodiesterase-4 (PDE-4) inhibitor, is approved for the treatment of chronic obstructive pulmonary disease (COPD) (1). In experimental studies, PDE-4 activity was elevated in psoriasis lesions (2). Roflumilast has a favorable safety profile and has the potential to improve not only skin manifestations but also psoriatic arthritis. No laboratory monitoring is required (2). When roflumilast is used in combination with isoniazid in both acute and chronic murine models of tuberculosis, a decrease in the pulmonary bacillary burden is observed; consequently, roflumilast may be a suitable therapeutic alternative in patients with possible tuberculosis (3).

Oral roflumilast has been used in diverse skin diseases, including psoriasis (Table 1), suppurative hidradenitis (4) or aphthosis (5) with apparently good clinical outcomes, good tolerability and safety. It may also be beneficial in comorbidities such as metabolic syndrome or COPD (6–9). In a recent clinical trial of oral roflumilast for the treatment of moderate to severe psoriasis, oral roflumilast (500 μg once daily) was effective and safe over 24 weeks (10). A topical presentation of roflumilast is approved by the U.S. Food and Drug Administration (FDA), for the treatment of mild to moderate plaque psoriasis and intertriginous psoriasis, with a clearing rate of almost 45% at week 52 (11).

Table 1. Previously reported cases of psoriasis treated with oral roflumilast.

	Type of study	Age	Sex	Psoriasis type	Comorbidities	Side effects	Outcome
Gyldenløve et al. (2023)	Clinical trial	Median of 38 years	15 Male 8 female	Plaque psoriasis	Not reported	Mainly weight loss in 19 patients, decreased appetite in 14, nausea in 12, headache in 11 and abdominal pain in 9.	At week 24: 10 patients PASI 75 5 patients PASI 90 2 patients PASI 100
Gyldenløve et al. (2023)	Case report	48	Male	Plaque psoriasis	Overweight and obstructive lung disease	Weight reduction and transient gastrointestinal symptoms	Complete clearance after 6 months.
Ring et al. (2022)	Case report	54	Male	Plaque psoriasis.	Overweight and suppurative hidradenitis.	Weight reduction.	Complete clearing of psoriasis and improvement of hidradenitis after 5 months.
Michels et al. (2017)	Case report	59	Male	Plaque psoriasis, erythroderma	Chronic obstructive pulmonary disease	Not reported.	Improvement (treated as well with triamcinolone and intravenous methylprednisolone, but still presenting some plaques.

No special locations such as genital area, palms and soles or scalp were described as affected.

Oral roflumilast was rapidly effective for our patient with psoriasis who was refractory to topical therapy. On the basis of the limited evidence available to date, this drug may also be suitable for psoriasis patients with latent tuberculosis. Oral roflumilast can be an easy-to-prescribe alternative in cases where access to other more expensive therapies is limited.

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Data sharing not applicable – no new data generated.

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