An oral interleukin-23 receptor antagonist alleviated the course of psoriasis
The second phase of the clinical trial of JNJ-77242113 - an antagonist of the interleukin-23 receptor - showed that taking this drug reduced the area of psoriasis lesions and the degree of its symptoms. The greatest effect was observed at a dosage of 200 milligrams of the drug per day. The results of the study were published in The New England Journal of Medicine.
Psoriasis is a multisystem immune-mediated inflammatory disease that predominantly affects the skin and joints and increases the risk of atherosclerosis. Although the pathogenesis of this disease is not fully understood, it is known that interleukin-23 plays a key role in the activation of pathogenic T lymphocytes. This knowledge has come in handy for the development of new psoriasis treatments using monoclonal antibodies, which are considered safer than classical therapies for the disease.
However, such biologic drugs need to be administered intravenously or subcutaneously, which limits their widespread use. Therefore, there is a need for effective oral targeted therapies for psoriasis. JNJ-77242113 is an oral interleukin-23 receptor antagonist peptide that selectively and effectively blocks interleukin-23 signaling and the production of downstream cytokines.
Robert Bissonnette of Innovaderm Research Collaboration and colleagues conducted a phase II clinical trial of JNJ-77242113, in which the researchers sought an effective and safe dosage of the drug. Among the 255 patients randomized, all received at least one dose of the drug or a placebo. Overall, 24 patients (nine percent) discontinued treatment. The mean duration of psoriasis was 18.2 ± 12.79 years, and the mean total score on the PASI scale, which is used to assess the severity of skin lesions in psoriasis and disease activity, was 19.05 ± 5.83.
Researchers reported a significant dose-response relationship at week 16 (p < 0.001). At week 16, the percentage of patients with a response to PASI 75 was 37 percent among patients in the 25 milligrams once daily group, 51 percent in the 25 milligrams twice daily group, 58 percent in the 50 milligrams once daily group, 65 percent in the 100 milligrams once daily group and 79 percent in the 100 milligrams twice daily group. Other assessments of psoriasis severity showed similar relationships. In all study groups, however, JNJ-77242113 administration was associated with lower serum defensin levels, indicating a reduction in the activity of the inflammatory autoimmune process. However, this level reduction was stronger in the highest dosage group.
Similar relationships were observed in psoriasis severity questionnaires. Overall, three serious adverse events were reported: a case of covida (100 milligrams once daily), an infected cyst (50 milligrams once daily), and a suicide attempt (100 milligrams once daily). However, there was no association between drug dosage and risk of side effects.
If further phases of research are favorable, JNJ-77242113 may become the first highly effective and safe oral drug for the treatment of psoriasis.