With recent advances in the understanding of psoriatic disease, it is increasingly considered a systemic inflammatory condition rather than limited to the skin and joints. A variety of biologics are available today for the treatment of psoriasis, but with them, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities differ. We designed an observational, non-interventional, retrospective study of patients with severe psoriasis receiving biologic treatment with IL-17 inhibitors and aimed to investigate the correlations between etiopathogenic factors and the efficacy and persistence of these therapies in a group of psoriasis patients from Romania. Study results show that patients treated with ixekizumab had better persistence and high adherence compared to those treated with secukinumab. In this study, ixekizumab demonstrated lower risks of non-persistence, discontinuation, and switching and a higher likelihood of high adherence compared with secukinumab. This study contributes to the understanding of the persistence of anti-IL17 biologic therapies in psoriasis and the factors that may influence it.
Melanoma outcome seems different between females and males, with a potential protective role of estrogen (E) through estrogen receptors (ER) expression into the tumor. In the study of ERs, both alfa (ERα) and beta (ERβ) is a well-known endocrine elements in non-melanoma tumors, like mammary and endometrial cancer. Immunohistochemistry (IHC) assessment of melanoma concerning ERs represents a path to explore the tumor profile to provide useful information concerning the prognostic and potential adjuvant treatment. Currently, this is not a routine practice, nor a mandatory step for deciding the medical therapy. Typically, IHCs are based on usual kits for mammary tumors regarding ERs configuration. Prior/concomitant use of oral contraceptives and hormonal replacement therapy is not correlated with a better prognostic in melanoma; neither have they represented a contraindication for survivors of melanoma; a subset of tumors might present a higher ER expression which is potentially targeted by the hormone-based treatment as SERMs (Selective Estrogen Receptors Modulator), for instance, tamoxifen. Experimental studies on melanoma cell lines confirmed the anti-tumor activity of ERβ which might function as a prognostic marker. G-protein-coupled estrogen receptors in melanocytes and keratinocytes might be involved, too. Additional crosstalk of TGF-β (Transforming Growth Factor β), respective IGF1 (Insulin-like Growth Factor), and ERα expression are involved in tumorigenic pathways. Recent preclinical studies showed the potential benefits of diarylpropionitrile, a selective agonist of ERβ; pyrazole derivates 21-23 can block ERs. Murine melanoma models showed the interference of anti-estrogenic medication (like molecule fulvestrant) to enhance immune checkpoint blockade, a modern approach to solid cancers. The proliferation of melanoma might be partially explained by ERs; whether this is generally applicable or there is a subgroup of tumors particularly related to E status is still debatable. The subject of E status in melanoma is far from clear at this point and further studies are necessary concerning this particular issue to implement it as a practical approach in the daily management of a disease that still has a very severe prognostic nowadays.
Psoriasis is a chronic, immune-mediated inflammatory disease that significantly affects a patient’s quality of life. Several systemic complications can influence disease progression and response to treatment. Biological therapy is considered the most effective therapeutic option in treating moderate to severe forms of psoriasis. The success of therapy may depend on its persistence, also known as drug survival. The dermatologist needs to be aware of comorbidities and factors that influence the persistence or discontinuation of biological treatment to make appropriate treatment decisions. We have identified several studies on the persistence of biologic therapy or drug survival in patients with psoriasis and summarized some of the most important issues known to date. In several recently published studies, the survival of ustekinumab is better than TNF‐α inhibitors but lower than ixekizumab. Notably, the studies were performed on a limited number of patients and follow-up time. Moreover, secukinumab appears to have a shorter drug survival than other biological agents, especially in patients with biological experience. A real indicator of therapeutic success could be a high quality of life. Female gender and obesity have been consistently highlighted among the predictors of treatment discontinuation, while psoriatic arthritis could be a predictor of persistence and maintenance of biological therapy. We are currently aiming to improve the therapy for patients treated with biological agents to reduce the pressure on the national public health system.
Psoriasis is a chronic inflammatory disease, with multisystemic implications and genetic predisposition, characterized by the development of erythematous, scaling plaques on the skin. Management of moderate to severe psoriasis vulgaris may involve a biological treatment that suppresses the immune system. Because of this, the patients with psoriasis on an immunosuppressive treatment are theoretically at an increased risk of infections, including SARS-CoV- 2 infection. SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is responsible for the current pandemic. In Romania, COVID-19 (Coronavirus Disease 19) was first reported on February 26, 2020, by confirming the first patient with SARS-CoV-2 by RT-PCR method. COVID-19 progression was divided into three phases: early infection, pulmonary phase, and hyperinflammatory phase. Although the inhibition of pro-inflammatory cytokines by biologic therapy is detrimental in the viral phase, it seems to be beneficial in the hyperinflammatory phase, by protecting the patients with psoriasis in progressing towards extra-pulmonary manifestations and death. Analyzing the evolution of the 8 cases of patients from our dermatology department – Colentina Clinical Hospital, with generalized psoriasis vulgaris on biologic immunosuppressive treatment and SARS-CoV-2 infection, we observed that they did not develop a more severe form of COVID-19 than the general population. Patients on biologic immunosuppressive treatment are more susceptible to the development of infections, including by SARS-CoV-2, but it was found that the biologic therapy can protect against a more severe type of COVID-19.
