# Challenges and Future Trends in the Treatment of Psoriasis [PERSON] and [PERSON]
## 3 Challenges in the Current Treatment of Psoriasis  
Biologic agents have revolutionized the treatment landscape for psoriasis, particularly in patients with moderate-to-severe disease. However, despite their effectiveness, several challenges and limitations persist in the use of these medications. One of the major challenges is the occurrence of primary and secondary treatment failures or inadequate responses to initial treatment. While biologic agents have shown high response rates, there is a subset of patients who do not respond to these treatments, leading to primary treatment failure [37]. This highlights the need for better predictors of treatment response to identify those patients who are more likely to benefit from a particular biologic agent. To address this challenge, the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has recently convened to identify and study factors that contribute to treatment non-response. The details will be analyzed further in the following sections. Secondary failure is defined as decreased efficacy in a patient who initially responded well to a treatment. One possible reason for the decrease in effectiveness is the development of neutralizing antibodies in patients. In other immune-mediated diseases, combining biologic agents with methotrexate has been shown to improve the longevity of biologic drug response [38]. However, there is limited reported evidence on the use of methotrexate, a conventional systemic therapy, in combination with biologics specifically for psoriasis treatment, and there are currently no randomized controlled trials (RCTs) to support a recommendation for combination therapy [39]. Similarly, switching biologics may also be a good option for secondary failure. To date, several studies on biologic change for psoriasis treatment have been published. The most frequent reason for discontinuing initial treatment was inefficacy. Patients who switched to a different biologic agent demonstrated comparable improvements in PASI scores to biologic-naive patients. Transitioning to a second biologic treatment due to inefficacy or adverse events associated with the initial one has the potential to enhance psoriasis management [40; 41; 42; 43]. One study examined the real-world switching patterns in patients with psoriasis who were treated with biologic medications in the United States. They found that the overall rates of switching were 14.4% at 12 months and 26.0% at 24 months. IL-23 inhibitors were associated with the lowest risk of switching compared to TNF, IL-17, and IL-12/23 inhibitors. Factors such as prior use of targeted immune modulators, age, and female gender were identified as predictors of switching [43]. Considering a switch to a different biologic agent, the optimal interval between discontinuation of the previous medication and initiation of a new biologic is not well established. While the half-life of biologic agents can serve as a reference, individualized approaches are often required based on the patient's disease severity, response to prior treatment, and expert opinion. Another significant concern associated with biologic therapies is their high cost. These medications are often expensive, placing a financial burden on patients and healthcare systems. In a survey of patients with psoriasis, the majority of patients answered that they needed a more cost-effective option in treatment [45]. However, as the patents for some biologic agents approach expiration, the development of biosimilars offers the potential for reduced drug costs. Their availability can enhance cost-effectiveness, improve accessibility, and provide additional treatment options for patients. Biosimilars to the TNF-\(\alpha\) inhibitor showed similar effects to the originator [46; 47]. Accordingly, biosimilars to the IL-17 inhibitor and IL-23 inhibitor are expected to produce similar effects.