# Challenges and Future Trends in the Treatment of Psoriasis [PERSON] and [PERSON]
## 2 Current Treatment Guidelines
### Treatments for Moderate-to-Severe Poriasis
#### 2.2.3 Biologics for the Treatment of Moderate-to-Severe Plaque Psoriasis  
* TNF-\(\alpha\) inhibitors  
TNF-\(\alpha\) inhibitors are a class of medications that target tumor necrosis factor-alpha (TNF-\(\alpha\)), a cytokine involved in inflammation. Three commonly used TNF-\(\alpha\) inhibitors are etanercept, infliximab, and adalimumab. The response to TNF-\(\alpha\) inhibitors is typically observed after 12 to 16 weeks of continuous treatment, except for infliximab, where response is experienced after 8 to 10 weeks. Their efficacies and long-term safety profiles have been demonstrated in moderate-to-severe psoriasis [27; 28]. However, many severe adverse events were reported, such as serious infections, reactivation of hepatitis B and C, tuberculosis, drug-induced lupus, and demyelinating central nervous system disorders [29; 30]. TNF-\(\alpha\) inhibitors may be beneficial for patients with a history of inflammatory bowel disease, and certain inhibitors are approved for its treatment.  
* IL-23 inhibitors  
Ustekinumab, guselkumab, risankizumab, and tildrakizumab are effective IL23 inhibitors used in the treatment of psoriasis. Mirikizumab is for use in late-phase development. Ustekinumab is the only biologic that targets both IL-12 and IL-23 by inhibiting their shared p40 subunit. In clinical studies, ustekinumab at doses of 45 mg and 90 mg showed PASI 75 response rates of 67.5% and 73.8%, respectively, at week 12. Other IL-23 inhibitors also demonstrate robust efficacy, acceptable safety profiles, and convenient dosing regimens. Guselkumab at 100 mg demonstrated PASI 75/90/100 response rates of 91.2%/73.3%/37.4%, respectively, at week 16, while risankizumab at 150 mg showed rates of 90.8%/74.8%/50.7%. Tildrakizumab at 100 mg exhibited respective PASI 75/90/100 response rates of 77%/54%/23% at week 28 [22]. Safety profiles are similarly acceptable,with no increased risk of serious infections or malignancies. Common side effects included nasopharyngealitis, upper respiratory tract infection, headache, and fatigue.
* IL-17 inhibitors target either the IL-17 ligand or its receptor. Secukinumab and izekizumab inhibit IL-17A, while bimekizumab inhibits both IL-17A and IL-17F. Brodalumab targets IL-17 receptor \(\alpha\). IL-17 inhibitors have a rapid onset of action, strong response, and sustainable efficacy for plaque psoriasis. Secukinumab at 300 mg demonstrated PASI 75/90/100 response rates of 77.1%/54%/24%, respectively, at week 16, while izekizumab at 80 mg after an initial 160 mg showed rates of 90%/70%/40%, and brodalumab at 210 mg showed rates of 83%/70%/42% [31; 32; 33]. They are also approved for psoriatic arthritis. In addition, secukinumab and izekizumab have been reported to be particularly effective in treating nail psoriasis. The safety profile of IL-17 inhibitors is acceptable, with no increased risk of serious infections or malignancy. However, mucocutaneous candidiasis and exacerbation of inflammatory bowel disease have been reported [34; 35]. Common adverse reactions include upper respiratory tract infections and injection site reactions. A case of suicidal ideation has been reported in a patient treated with brodalumab, and the relationship between the two has not yet been clarified [36].