Psoriasis can occur in people of all age groups, regardless of gender, and those with a family history of the disease are more likely to develop it than the general population. The main symptoms include scaly erythema on the skin accompanied by massive desquamation, itching, pain, etc. Some patients may also experience joint damage, and in severe cases, joint deformity may occur. Due to the complex pathogenesis of psoriasis, the fundamental mechanism has not been fully clarified by current medical methods. However, it is generally believed that the main cause is the disorder of the patient's autoimmune mechanism. The main treatment methods mainly include vitamins, antibiotics, targeted immune preparation biological drugs or chemical drugs.
In the treatment of this disease, biological agents have always had unique advantages. Since the 20th century, scientists have been exploring its pathogenesis, ranging from the early abnormal keratinocytes, the imbalance of helper T cells, to the later research on tumor necrosis factor - α (TNF - α), IL - 17, IL - 23, which has remained a hot topic.
At present, the biological agents that can be used for the treatment of this disease and have been approved for marketing worldwide can be divided into interleukin - based, TNF - α - based and T cell inhibitory types. For example, adalimumab, certolizumab pegol and golimumab targeting TNF - α; secukinumab, ixekizumab and netakimab targeting IL - 17A. Among them, netakimab is a chimeric IgG1 nanobody targeting IL - 17A, which has been marketed in Russia. This drug not only has a therapeutic effect on psoriasis and its associated arthritis, but also can be used for the treatment of ankylosing spondylitis.
Biological Agents and Targets for Targeted Treatment of Psoriasis [1]
With the continuous development of biological agents, among the biological agents currently being developed for the treatment of psoriasis that have entered Phase II or III clinical trials and shown effectiveness, the research mainly focuses on targeting the IL - 17 signaling pathway and IL - 23.
A humanized monoclonal antibody against IL - 36R, imsidolimab, showed in Phase II clinical trials that after treatment at weeks 1, 4 and 16, the severity index of patients decreased by 29%, 54% and 98% respectively, and the lesional area decreased by 60%, 94% and 98% respectively. The drug had good tolerability, and only mild adverse events were reported in the adverse reaction reports. Another monoclonal antibody against IL - 17A, vunakizumab, also showed good tolerability in Phase II trials, and no oral candidiasis, malignant tumors, inflammatory bowel disease, major adverse cardiac events or unexpected adverse safety events were found [1].
Various studies have shown that biological agents have a significant therapeutic effect on psoriasis. However, some drugs still fail to achieve the target efficacy in the treatment trials of the tested patients. For example, adalimumab is prone to induce the formation of anti - drug antibodies (ADAs) during the long - term administration for the treatment of psoriatic arthritis, and the gradual accumulation of ADAs eventually leads to the loss of the drug's efficacy [4]. In contrast, ozoralizumab, another drug that can also be used for the treatment of autoimmune arthritis, was developed by Ablynx. It is a humanized nanobody against TNF - α, composed of two anti - human TNF - α nanobodies and one anti - human serum albumin (HSA) nanobody. It showed good affinity and tolerability in clinical trials, and no obvious formation of ADAs was found.
In the treatment of psoriasis, sonelokimab is a nanobody composed of three sequence - optimized monovalent moieties, which is used to block IL - 17A/F and its heterodimers. In the Phase II clinical controlled trial, its response rates were 90.2%, 76.5% and 33.3% respectively, while those of the secukinumab control group were 90.6%, 64.2% and 28.3% respectively. The 52 - week treatment trial found that the safety of sonelokimab was similar to that of secukinumab, but its efficacy and onset speed were better. In addition, secukinumab may have a higher and more frequent incidence of oral fungal infections [5].
Therefore, biological agents are in urgent need of new drug development strategies to prolong the treatment duration and avoid the loss of efficacy. The various advantages of nanobodies are widely favored in the field of biological agents. Their low immunogenicity, easy modification and strong targeting ability make nanobodies far superior to traditional antibodies in many aspects, and they can also be regarded as a new research and development strategy for biological agents.
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