Combining Systemic Therapies in Psoriasis and Atopic Dermatitis

James Song, MD, director of clinical research at Frontier Dermatology Partners in Seattle, Washington,provided comprehensive insights into the strategic combination of systemic therapies for treating psoriasis (PsO) and atopic dermatitis (AD). His presentation at the 2024 Fall Clinical Dermatology Conference for PAs and NPs highlighted the multifaceted approach required to enhance treatment efficacy, address comorbidities, and improve patient safety.¹ 

Rationale for Combining Systemic Therapies

The primary motivation behind combining systemic therapies is to enhance treatment outcomes. Patients often experience primary or secondary treatment failure, where the initial therapeutic response is inadequate or diminishes over time. Additionally, flares of PsO and AD can be better managed through a combination approach. Comorbid conditions, such as psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), uveitis, inflammatory bowel disease (IBD), and hidradenitis suppurativa (HS), also necessitate a more comprehensive treatment plan that systemic combinations can provide.

Newer biologics are significantly more effective and longer-lasting compared to first-generation biologics. With a wider array of treatment options now available, switching therapies has become easier. Consequently, the use of combination therapy is decreasing.²

Moreover, combining systemic therapies can potentially lower the dosage of the more toxic drugs involved, thereby improving the overall safety profile for the patient. Transitioning patients from one systemic therapy to another, especially in cases with persistent special site areas, is another critical aspect where combination therapies prove beneficial.

Key Considerations in Combination Therapy

Song emphasized several crucial considerations when combining systemic therapies. First and foremost, he says it is vital to ensure an accurate diagnosis. Misdiagnosis can lead to ineffective treatment plans. For example, conditions like cutaneous T-cell lymphoma (CTCL) can mimic PsO and AD, necessitating multiple biopsies to confirm diagnosis.^3-4

The modern era of dermatology has introduced newer biologics that are far more effective and durable than the first-generation biologics. This development has increased the available treatment options, making it easier to switch therapies when necessary. However, despite the advancements, combination therapy remains underutilized, primarily due to concerns about additive or synergistic toxicities.

Strategies for Effective Combination Therapy

When combining systemic therapies, Song recommended avoiding duplication of the same therapeutic pathway and being vigilant about potential additive toxicities, which require more frequent monitoring. A strategic approach involves pairing long half-life drugs (biologics) with short half-life drugs (cs/tsDMARDs). Drawing from successful practices in other diseases can also guide effective combinations.

Evidence and Clinical Practices

The data on combining systemic therapies in PsO is limited but growing. The most common combinations involve biologics with cs/tsDMARDs or retinoids, with methotrexate (MTX) often used in combination with TNFα inhibitors to decrease immunogenicity and improve drug survivability. The benefit of combining MTX with IL-17 or IL-23 inhibitors, however, remains less clear.⁵

Case studies from Song’s clinic provided insights on how a combination therapy can be successful. For instance, one patient with Crohn's disease and PsO flares managed well with a combination of ustekinumab and MTX after failing adalimumab and infliximab. Another example involves the use of acitretin with TNFα or IL-12/23 inhibitors to manage palmoplantar pustulosis and prevent eruptive squamous cell carcinomas.

Concomitant PsO and AD

Historically, PsO and AD were considered immunological opposites. However, Song noted the emerging concept of "PsEma" or "eczematized psoriasis," where overlapping features of PsO and eczema necessitate a nuanced treatment approach. Cases of phenotypic switching and mixed presentations are not uncommon, particularly among Asian patients.⁶

Song presented a patient case dual biologic therapy has shown promise. For example, a patient withPsO unresponsive to certolizumab achieved significant improvement with the addition of upadacitinib. Similarly, another patient with both conditions responded well to a combination of risankizumab and dupilumab.

Pearls to Put into Practice

Song’s pearls for combining systemics include: avoiding the use of treatments that target the same pathway; being mindful of the potential for additive or synergistic toxicities, which necessitates more frequent monitoring (e.g., when combining methotrexate with acitretin or cyclosporine with TNF inhibitors); pairing long half-life drugs (biologics) with short half-life drugs (conventional or targeted synthetic DMARDs); and leveraging existing practices from other diseases rather than starting from scratch.

He also concluded by sharing tips to gain access to systemics for patients who need them. To secure biologic treatments for patients, he says dermatology clinicians should be prepared for a "peer-to-peer" discussion. “It's essential to know the relevant literature and use key references to support your case,” Song explained. Each treatment should be associated with the appropriate diagnosis, and collaboration with other specialists can be beneficial. For example, a dermatologist might prescribe a biologic for PsO, while a rheumatologist might handle PsA with PDE4 inhibitors or JAK inhibitors. Similarly, for PsO treated with deucravacitinib, a gastroenterologist might use TNF-alpha inhibitors, p19, p40 inhibitors, or JAK inhibitors for inflammatory bowel disease. Additionally, utilizing available samples can be helpful.

References

1. Song EJ. Combining Systemics in Psoriasis and Atopic Dermatitis. Presented at: 2024 Fall Clinical Dermatology Conference; May 31-June 2, 2024; Scottsdale, AZ.
2. Armstrong AW, Puig L, Joshi A, et al. Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis. JAMA Dermatol. 2020;156(3):258-269. doi:10.1001/jamadermatol.2019.4029
3. De A, Raychaudhury T, Rajagopalan M, Sarda A, Sharma N. A case of cutaneous T-cell Lymphoma, masquerading as psoriasis, was given etanercept and secukinumab: emphasizing the need for biopsy confirmation before starting biologics. Indian J Dermatol. 2017;62(5):533-535. doi:10.4103/ijd.IJD_311_17
4. Miller AC, Mattia A, Thompson A, Temiz LA, Adjei S, Tyring SK. Psoriasiform mycosis fungoides-cutaneous T-cell lymphoma in an African American. JAAD Case Rep. 2023;38:17-19. Published 2023 Jun 5. doi:10.1016/j.jdcr.2023.05.035
5. Manders SH, van de Laar MA, Rongen-van Dartel SA, et al. Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry. RMD Open. 2015;1(1):e000147. Published 2015 Oct 8. doi:10.1136/rmdopen-2015-000147
6. Balato A, Zink A, Babino G, et al. The Impact of Psoriasis and Atopic Dermatitis on Quality of Life: A Literature Research on Biomarkers. Life (Basel). 2022;12(12):2026. Published 2022 Dec 5. doi:10.3390/life12122026