State of the art and pharmacological pipeline of biologics for chronic plaque psoriasis.

Psoriasis is a chronic immune-mediated inflammatory skin disease with a multifactorial aetiology and a strong genetic predisposition. In the last two decades, a better understanding of psoriasis pathophysiology allowed the development of targeted therapies, including biologics and small molecules. As to biologics, different classes are now available including tumour necrosis factor (TNF)-α interleukin (IL)-12/23, IL-17 and IL-23 inhibitors. TNF-α inhibitors were the first biologics introduced for psoriasis treatment and include etanercept, infliximab, adalimumab and certolizumab. The class of IL-17 inhibitors encompasses secukinumab, ixekizumab, brodalumab, bimekizumab, netakimab and M1095. The novel class of IL-23 inhibitors, including guselkumab, risankizumab and tildrakizumab, bind the p19 subunit of IL-23 in order to prevent the activation of IL-23 receptor. They differ from ustekinumab as the latter antibody inhibits the p40 subunit shared by both IL-23 and IL-12. The availability of biosimilars at much lower cost compared to originators is dramatically changing the access of patients to these treatments. In the coming years, studies will progress to identify subgroups of patients based on biomarkers for a more personalized treatment approach.

Delirium in acute promyelocytic leukemia patients: two case reports.

BACKGROUND: Delirium is a frequently misdiagnosed and inadequately treated neuropsychiatric complication most commonly observed in terminally ill cancer patients. To our knowledge this is the first report describing delirium in two patients aged less than 60 years and enrolled in an intensive chemotherapeutic protocol for acute promyelocytic leukemia. CASE PRESENTATION: Two female Caucasian acute promyelocytic leukemia patients aged 46 and 56 years developed delirium during their induction treatment with all-trans retinoic acid and idarubicin. In both cases symptoms were initially attributed to all-trans retinoic acid that was therefore immediately suspended. In these two patients several situations may have contribute to the delirium: in patient 1 a previous psychiatric disorder, concomitant treatments with steroids and benzodiazepines, a severe infection and central nervous system bleeding while in patient 2 steroid treatment and isolation. In patient 1 delirium was treated with short-term low-doses of haloperidol while in patient 2 non-pharmacologic interventions had a beneficial role. When the diagnosis of delirium was clear, induction treatment was resumed and both patients completed their therapeutic program without any relapse of the psychiatric symptoms. Both patients are alive and in complete remission as far as their leukemia is concerned. CONCLUSIONS: We suggest that patients with acute promyelocytic leukemia eligible to intensive chemotherapy should be carefully evaluated by a multisciplinary team including psychiatrists in order to early recognize symptoms of delirium and avoid inadequate treatments. In case of delirium, both pharmacologic and non-pharmacologic interventions may be considered.