Topicals for Psoriasis: Classical Drugs, New Concepts, and New Medications

Classical topical therapies

Topical corticosteroids. Corticosteroids exert antiinflammatory, antimitotic, apoptotic, vasoconstrictive, and immunomodulatory effects that reduce plaques by dampening immune signaling and keratinocyte proliferation.⁶ Mainly, high-potency steroids are used. Betamethasone dipropionate 0.05% (cream/solution), clobetasol propionate 0.05% (cream/ointment/solution/foam), and halobetasol propionate 0.05% (cream) demonstrate clear or almost clear responses in approximately 35-70% of patients by physician global assessment (PGA) or investigator global assessment (IGA) of psoriasis, although Psoriasis Area Severity Index (PASI) is less consistently reported.^7,8 Low- and medium-strength topical steroids could be used on the face and folds (groin and axillae), and transition to CNI may be considered. Cutaneous atrophy may limit continuous use beyond 4-8 weeks. Other considerations such as safety during pregnancy or association with systemic therapy or phototherapy have not been assessed.

Vitamin D analogs. Vitamin D analogs modulate keratinocyte proliferation/differentiation and reduce proinflammatory cytokines in psoriatic plaques. Calcitriol 0.0003%, calcipotriol 0.005%, and tacalcitol 0.0004% creams and ointments are well tolerated and suitable for long-term use, with clear/almost clear rates around 10-40% by PGA/IGA.⁹ Burning or stinging may occur.

Fixed combinations (corticosteroid + vitamin D analog). Fixed combinations of betamethasone dipropionate 0.05% and calcipotriol 0.005% (ointment, gel, and foam) improve efficacy, achieving clear/almost clear response in ~60-90% of patients in clinical studies, with once-daily regimens and lower atrophy rates during intermittent or proactive use up to 52 weeks.⁹ These products have been a cornerstone of topical therapy for years.

Other topical agents. Topical retinoids (tazarotene 0.03-0.1% gel) show insufficient efficacy as monotherapy and are best used on thick skin (eg, palms, soles) combined with high-potency steroids.¹⁰ Salicylic acid, coal tar, and CNI (tacrolimus and pimecrolimus) have limited PsO-specific evidence and are typically adjuvants.¹⁰ These agents are particularly useful for treating PsO in sensitive areas (eg, face, genitals, intertriginous folds). Burning or stinging are more common with retinoids and CNI. Moisturizers, particularly with urea 10-20%, are recommended as part of skin care.

Practical assessment and prescribing (classical agents)

When choosing a topical agent, consider age (particularly for children and older adults) in terms of systemic absorption in thin skin and risk of atrophy. Adherence to daily treatment application and dosing frequency should be considered.¹¹

Anatomic sites such as the trunk, limbs, palm/soles, and scalp could be treated with high-potency steroids, although these should be avoided for the groin and face.^11,12

Regarding the vehicle, ointments are preferred for very dry or scaled lesions; creams or foams for extended lesions in the trunk and limbs; and solution, liquid gels, or shampoo for the scalp.^11,12

Safety counseling about adverse events is advised, particularly for topical corticosteroids (eg, atrophy, telangiectasias, striae, perioral dermatitis, systemic absorption with extensive or high-potency use), where strategies such as intermittent use or steroid-sparing agents should be assessed.¹³

In terms of duration, treatment includes continuous use of corticosteroids up to 4-8 weeks once clearance is achieved. Then, intermittent and/or proactive treatment 1-2 times per week or nonsteroidal topical treatments are recommended. Other agents such as nonsteroidal antiinflammatory topical agents could be used until 8-16 weeks.¹⁴

After 8-12 weeks, clinical response should be assessed. Current goals include IGA 0-1, PASI < 3, and Dermatology Life Quality Index (DLQI) < 5. Consider high-impact areas such as face, palms/soles, or groin, even when PASI or body surface area (BSA) are otherwise low.¹⁵ If goals are not achieved, escalation to phototherapy or systemic therapy is recommended. For recommendations, refer to Table 1.

Unmet needs with classical therapy

Topicals are not only used in mild disease but are also frequently used as adjuncts to systemic therapy in patients with more extensive disease, although no specific studies have been carried out to assess their efficacy in this scenario. Therefore, options remain limited and may be unaffordable for some patients. Safety concerns (eg, steroid atrophy) persist, long-term comparative data are scarce, and disease modification has not been established. New treatments should expand mechanisms, improve adherence, employ other vehicles (foam/spray, lacquer, solution) to improve adherence and cosmesis, and reduce steroid burden.^3,4

Some patients experience treatment burden and adherence barriers. Many patients describe topical therapy as difficult to sustain (owing to frequent application, greasiness, time burden, messiness, interference with daily routines, etc.). This should be acknowledged and tied to practical prescribing choices (eg, vehicle selection, simplified regimens, maintenance strategies, and newer nonsteroidal options when appropriate).¹⁶

New treatments and concepts

Topical therapy remains a cornerstone for localized/mild PsO. Among nonsteroidal agents, tapinarof (AhR agonist) down-modulates inflammatory pathways and normalizes barrier proteins (filaggrin/loricrin) with downstream effects on interleukin 17 signaling.^14,16 In PSOARING 1/2, tapinarof 1% cream once daily was superior to vehicle cream at 12 weeks for PGA 0/1 (≥ 2-grade improvement), with concordant PASI, BSA, and patient-reported outcome benefits, supporting a steroid-sparing role when long-term control and good cutaneous tolerability are desired.¹⁷

In parallel, roflumilast (PDE4i) cream offers once-daily dosing and a pragmatic steroid-sparing profile. DERMIS-1/2 showed its significant superiority vs vehicle cream for IGA success at 8 weeks, consistent pruritus improvement, and good performance in high-impact areas (eg, intertriginous sites), with favorable local tolerability.¹⁸ Complementary therapeutic forms (eg, 0.3% foam for scalp and hair-bearing regions) support utility in difficult locations and early symptom relief. Longer-term extensions report low rates of serious adverse events without emergent class-specific signals.¹⁸

In general, persistent skin atrophy was not reported in trials of newer agents, providing a better efficacy/safety balance compared with topical steroids.

Practice points and outlook

We emphasize 3 messages for daily practice: (1) topical therapy remains central for mild or localized PsO; (2) newer nonsteroidals such as tapinarof (AhR agonist) and roflumilast (PDE4i) creams provide targeted mechanisms with once-daily dosing and the potential for better adherence; and (3) appropriate use of topical steroids should be addressed with respect to potency, duration, site-specific safety, tapering, adherence, patient education, or monitoring for adverse effects. The use of topical Janus kinase inhibitors and phenotype-tailored approaches may be considered. Collectively, these trends support a more precise, steroid-sparing framework that is useful as monotherapy in mild disease or as an adjunct to systemic regimens, aligning with goals of clearing skin and improving quality of life.^17-19

Many barriers to effective topical therapy still exist. Affordability is a key barrier, in which high acquisition costs for the novel topicals may limit real-world access and adherence unless supported by favorable pricing, reimbursement, and formulary inclusion. Other issues include treatment complexity, adherence challenges, vehicle acceptability, difficulty treating high-impact sites, time burden, provider-level instruction, insurance restrictions, and limited availability of newer agents in many regions. Topical steroids remain the available, affordable treatment in many regions. Topical therapies continue to be frequently prescribed in PsO, and we must seek their appropriate, effective, and safe use.