Recalcitrant psoriasis responding to new bilogic drug: Ustekinumab

Abstract

To the Editor: Psoriasis is a chronic inflammatory skin disease affecting 2% of the population.1 This disease affects the skin and is associated with significant patient morbidity. Conventional topical and systemic treatment options are numerous with varying degrees of success and rapidity of action. The immunological pathogenesis of this condition has substantially grown in the recent years. All the advances have led to the development of biologic agents that have dramatically altered the treatment of moderateto-severe psoriasis. Most of these agents are tumor necrosis factor (TNF) alpha-blockers, such as etanercept, infliximab, and adalimumab, which have shown a notable efficacy in the treatment of this condition. A new class of biologic agent ustekinumab, an interleukin (IL)-12 and IL-23 antibody, has shown a significant improvement when treating psoriasis, without the safety concerns, such as risk of infections associated to the former biologic agents. We present a case of a patient with severe plaque psoriasis refractory to multiple therapies, with a good response to ustekinumab. A 56-year-old male presented to our hospital with recalcitrant plaque psoriasis for the last 40 years. The previous medical history showed smoking (1 pack per day), hypertension treated with enalapril 50 mg, and obesity (grade II). A positive family history of psoriasis was reported: his grandmother and sister had psoriasis. Over the years, our patient failed to respond to different topical and classic systemic therapies such as methotrexate and cyclosporine. In 2007, anti-TNF alpha-blockers, infliximab, and etanercept to standard doses, were also used in standard doses. Although they gave a significant improvement, the disease relapsed during the following months of treatment. On examination, severe scaly plaques involving trunk, arms, and legs were observed (Figure 1). Psoriasis Assessment Score Index (PASI) was 34.2. The clinical exam did not reveal the signs of concomitant psoriatic arthritis. For the evident difficulties in management, particularly the lack of long-term efficacy, we considered to initiate a treatment with ustekinumab. Before starting the new treatment, a complete laboratory with blood count and chest x-rays were performed. No significant alterations were found. According to the patient’s weight (108 kg), he was treated using 90 mg ustekinumab. A dramatic response was observed only 1 week after the first injection, reaching PASI 75 (Figure 2). On the following-up, the efficacy was maintained and no local subcutaneous reaction was observed in the injection site. Psoriasis is a chronic, relapsing immune-mediated inflammatory disease affecting the quality of life of patients with this condition. The first-line management of this condition is with topical treatments, including vitamin D analogues, topical steroids, tar-based preparations, dithranol, and salicylic acid.2 When no satisfactory result is achieved with these topical agents, systemic treatment may be initiated such as cyclosporine, methotrexate, and acitretin. Guidelines from the British Association of Dermatologists suggest that patients with psoriasis may be eligible to receive interventions with any of the 4 licensed biological agents (infliximab, etarnecept, adalimumab, and ustekinumab) when they fulfil either of the following specific criteria: (i) severe clinical disease, defined as PASI ≥10, (ii) intolerance to standard systemic therapy, (iii) contraindicated, or (iv) lack of response to standard systemic therapy. 3 Despite of all this full range of therapeutic approaches, the treatment of moderate-to-severe psoriasis can be challenging. As we stated previously, standard systemic therapies sometimes show initial efficacy in only a certain percentage of patients, whereas other patients are resistant to any kind of therapy. Our patient suffered from a severe form of psoriasis that was recalcitrant to other systemic therapies including anti-TNF alpha-blockers. Although the TNF-alpha has an important role in the pathogenesis of psoriasis,4 recent studies over the past 5 years have altered the view of psoriasis as a disease mediated primarily by more specific cytokines, including IL-23 and IL-12. Ustekinumab is a fully human monoclonal antibody that blocks these specific molecules, thus inhibiting proliferation of Th1 and Th17 T-cells. Such a unique mechanism of action leads to the rapid onset of clinical response after the initiation of treatment, with 60% of patients attaining Physician’s Global Assessment scores of “cleared” or “minimal” by week 12.5 Treatment with ustekinumab was very well tolerated in our case, and it resulted in a very rapid and maintained response without any side effect. In conclusion, ustekinumab provides an effective alternative to current anti-TNF alpha preparations in psoriasis refractory to other therapies.