Deucravacitinib and psoriasis: a sigh of relief

Abstract

Introduction and pathophysiology Psoriasis is a chronic inflammatory skin condition linked to numerous other medical disorders, such as cardiometabolic syndrome, depression, and psoriatic arthritis1. Around 125 million individuals on the planet are affected by psoriasis. Genetic factors mostly cause psoriasis, while environmental variables can aggravate the condition2. Moderate-to-severe psoriasis is present in ~25% of affected patients3. Greater than 80% of cases of psoriasis fall within the most frequent subtype, plaque psoriasis. Erythematous scaly plaques, which typically develop on extensor surfaces like the knees and the elbows are the hallmark of this subtype. Gluteal fold, intertriginous areas, soles, palms, and nails may also be impacted. Furthermore, impacted regions are typically clearly defined and frequently symmetrical. A feed-forward mechanism of inflammation, notably the type 17 T-helper cell (TH17) pathway, leads to the development of plaque psoriasis2. Patients with more severe cases of psoriasis experience a stronger psychological impact as a result of the disease. Up to 20% of psoriasis sufferers are more prone to experience depression and have suicidal thoughts that progress to actual suicide4. Treatment options for psoriasis Primary treatment options for psoriasis include phototherapy and topical and systemic treatments which can be utilized singly or in combination. Phototherapy is initiated when the disease is extensive and resistant to other therapies. Two types of phototherapies are used: psoralen combined with ultraviolet A irradiation (PUVA) and UVB irradiation. However, they cost expensive and proper facilities are required. Despite toxicity-reducing strategies such as combination therapy, some individuals experience major adverse effects from traditional psoriasis medicines5. A phosphodiesterase 4 (PDE-4) inhibitor, Apremilast was approved by the Food and Drug Administration (FDA) in 2014 to treat plaque psoriasis6. Inhibition of PDE4 raises intracellular cyclic adenosine monophosphate (cAMP) concentrations. However, Apremilast’s precise therapeutic activity in people with psoriatic arthritis and psoriasis is not fully understood, nor are the mechanisms through which it works7. Apremilast over 16 weeks demonstrated a clinically significant improvement in patients suffering from plaque psoriasis, as determined by the PASI score, according to ESTEEM 1 and ESTEEM 2, two clinical trials8,9. Apremilast was the only oral drug available for plaque psoriasis until now. On September 9, 2022—FDA approved deucravacitinib, as a new and better oral treatment option for adults suffering from moderate to severe plaque psoriasis10,11. Sotyktu (deucravacitinib) Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor that is selective and allosteric. It inhibits TYK2 by preferentially attaching to the pseudo kinase or unique regulatory domain instead of the enzyme’s active catalytic site12. The drug’s approval came after encouraging findings from the 2 clinical trials—POETYK PSO-1 and PSO-2, which found that Apremilast and placebo were less effective than deucravacitinib in treating 1684 adult patients with plaque psoriasis. In patients using deucravacitinib, oral ulcers, a rise in blood creatine phosphokinase, upper respiratory infections, pimples, and folliculitis were the most common side effects by the end of week 16 of these clinical studies. Deucravacitinib resulted in a rapid response and consistent trends in enhancements in many efficacy measurements as well as quality of life for those who have moderate to severe plaque psoriasis13. However, as per the manufacturer, Bristol Myers Squibb, combining Sotyktu (deucravacitinib) with other strong immunosuppressants is not advised. Conclusion For patients with psoriasis plaque who are not satisfied with conventional and topical therapies, the approval of deucravacitinib marks an exciting day, as it is the first oral medication authorized after a long time for plaque psoriasis. Given its track record of assisting patients in achieving smoother skin, as shown in the POETYK PSO clinical study, the drug deucravacitinib can change how psoriasis is managed and treated in a better way. Although the drug is contraindicated in pregnancy, information regarding the drug’s presence in human milk is lacking. Further research is required to comprehend better results in lactating women and widen the range as the drug has limitations in severe hepatic impairment10. Ethical approval Not applicable. Source of funding None. Author contributions MS.M. and F.A.: conceptualization. M.S.M., M.M.N.U., and S.T.A.: conducted the literature and drafting of the manuscript. M.A.S.: performed editing and supervision. All authors have read and agreed to the final version of the manuscript. Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor All authors take responsibility for the work, access to data and decision to publish.