Biologics have transformed the management of immune-mediated diseases, including psoriasis and psoriatic arthritis (PsA), offering significant improvements in patient outcomes and their quality of life 1•, 2. These therapies, primarily engineered monoclonal antibodies and fusion proteins, target specific proinflammatory mediators like cytokines or their receptors within the inflammatory cascade. However, monotherapy may not always be sufficient in psoriasis, particularly in cases of relapse despite ongoing treatment, concomitant PsA, or involvement of difficult-to-treat areas: the scalp, palmoplantar psoriasis, or the genital area. Patients with PsA often exhibit varying responses in their skin and joints to the same biologic [2]. In such cases, dual biologic therapy becomes a potential treatment option. Two or more agents with different mechanisms of action and safety profiles can be used to achieve and/or maintain adequate disease control while minimizing the toxicity of treatments. Choosing a combination regimen that maximizes safety and efficacy while considering patient usability and compliance can be a challenge.

Although combining two conventional systemic agents, such as acitretin and methotrexate, is generally discouraged due to a heightened risk of adverse effects, the concurrent use of phototherapy or traditional systemic treatments alongside biologic therapies is well established 3, 4. The addition of Narrowband Ultraviolet-B light to tumor necrosis factor-alpha (TNF-α) inhibitors or interleukin (IL)-12/23 inhibitors has been associated with more rapid and pronounced skin clearance. Furthermore, methotrexate is frequently combined with biologics, particularly in cases of concomitant psoriasis and PsA, to optimize control of joint symptoms.

However, dual biologic therapy remains infrequent in clinical practice. This review aims to explore the concept of dual immune inhibition with biologics as a therapeutic strategy for drug-resistant psoriatic disease, examining its potential benefits and clinical applications.