司库奇尤单抗治疗红皮病型银屑病一例并文献复习

报道一例司库奇尤单抗治疗红皮病型银屑病治疗效果并复习相关文献.41岁红皮病型银屑病男性患者,在排除肝炎、结核的基础上,经知情同意后,给予司库奇尤单抗标准方案:0～4周每周皮下注射300 mg,随后每4周注射300 mg.在第4周达到PASI 75,第8周达到PASI 100.随访32周未见明显复发及不良反应.     

Interleukin 17-A inhibition in the treatment of psoriasis

Interleukin (IL) 17-A appears to be integral to the pathogenesis of chronic plaque psoriasis. Recent clinical trials have shown that blockade of this cytokine with the biologic therapies—secukinumab, ixekizumab and brodalumab—have led to unprecedented treatment efficacy for psoriasis. In addition, their dual efficacy towards psoriatic arthritis increases their potential clinical utility and they promise to be an important treatment option for patients who have tumour necrosis factor inhibitor resistant disease. Here, we present the evidence for the high treatment efficacy of the IL-17A inhibitors but also discuss some potential questions and areas of research needed, including the lack of evidence behind the drug survival, immunogenicity and safety profile.     

Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: A 52‐week analysis from phase III open‐label multicenter Japanese study

Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human‐recombinant anti‐interleukin‐17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open‐label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co‐medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non‐responders were up‐titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as “worsened”, “no change”, “minimally improved”, “much improved” or “very much improved”. Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end‐point) with CGI evaluated as “very much improved” (n = 9) and “much improved” (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52‐week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.     

Beyond anti-TNF-α agents in psoriatic arthritis

Evaluation of: McInnes IB, Sieper J, Braun J et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, Phase II proof-of-concept trial. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-202646 (2013) (Epub ahead of print).

The IL-23/IL-17 pathway may be a novel therapeutic target for the treatment of psoriatic arthritis (PsA). The potential beneficial effect of Th-17A antagonism has been investigated by a randomized controlled trial in PsA patients with secukinumab, a fully human, high-affinity, monoclonal antibody in a cohort of patients with active PsA. Although this Phase II study presents bias that limits the ability of this drug to meet the primary and some secondary end points, the authors suggest that secukinumab may have biological effects and some clinical benefits in PsA patients. Further studies are required to demonstrate if the rationale to use drugs acting on the IL-23/IL-17 pathway is associated with relevant efficacy and safety in the treatment of PsA.     

Secukinumab (AIN457) for the treatment of psoriasis

Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.     

Effects of tumor necrosis factor‐α, interleukin‐23 and interleukin‐17A inhibitors on bodyweight and body mass index in patients with psoriasis

Treatment with tumor necrosis factor‐α inhibitors has been reported to cause weight gain in patients with psoriasis; however, limited information is available in terms of the effects of interleukin (IL)‐23 and IL‐17A inhibitors on bodyweight (BW) in patients with psoriasis. This study aimed to investigate the effects of infliximab, ustekinumab and secukinumab on BW and body mass index (BMI) in patients with psoriasis. We retrospectively examined changes in BW and BMI among patients treated with these biologics at our hospital. At baseline, no significant differences in BW and BMI were observed among the patients treated with infliximab (n = 18), ustekinumab (n = 30) or secukinumab (n = 20). After 7 months of the therapy, significant increases in mean BW (from 71.4 to 74.3 kg) and mean BMI (from 24.7 to 25.7) were observed in the patients treated with infliximab, whereas no significant changes were observed in those treated with ustekinumab (BW, from 70.3 to 70.1 kg; BMI, from 25.4 to 25.3) or secukinumab (BW, from 69.0 to 68.9 kg; BMI, from 25.2 to 25.2). There were no differences in the proportion of the patients who showed 75% or more improvement in the Psoriasis Area and Severity Index among the three groups. These results suggest that infliximab increases BW in the patients with psoriasis, whereas ustekinumab and secukinumab do not affect the BW in these patients.     

Status of a real-life cohort of patients with moderate-to-severe plaque psoriasis treated with secukinumab and considerations on the use of biological agents in the Covid-19 era

ABSTRACT

Introduction

In light of the current Covid-19 pandemic and the ongoing, extensive debate about the use of biological agents in psoriatic patients, we felt compelled to relate our experience in the use of secukinumab in the same cohort before and during the lockdown in Italy. Areas covered: Secukinumab was not discontinued, and there were no cases of confirmed infection with SARS-CoV-2 in this cohort. Expert opinion: In our practice, there is no evidence favoring the discontinuation of secukinumab in these patients. We also present a brief commentary on the use of biological agents in patients with moderate-to-severe plaque psoriasis.     

Biologic agents in nail psoriasis: efficacy data and considerations

Introduction: Nail psoriasis plays a major role in the overall assessment of psoriatic disease. Four biologic agents are officially labeled for the treatment of moderate to severe, stable plaque psoriasis (adalimumab, etanercept, infliximab, ustekinumab) and have enriched subsequently the therapeutic armamentarium against psoriatic nails. However, evidence for the efficacy of these agents for nail psoriasis is under investigation.

Areas covered: In this review an effort has been made to summarize evidence regarding the efficacy of biologics in nail psoriasis. A systemic search for reports of biologic agents in psoriatic patients with nail involvement was carried out (MEDLINE and CENTRAL in the Cochrane Library). Relevant data are thoroughly presented.

Expert opinion: All four biologic agents have shown efficacy on psoriatic nail disease. However, published data are heterogeneous, based on studies assessing the therapeutic efficacy with different scoring indexes and at different time points, depending on the time table of each drug administration. Therefore, the need for consensus on core outcome to be used is mandatory. Additionally, optimization of the scoring systems and the conduction of further trials of high quality and validity could lead to more accurate conclusions on the efficacy of biologic agents in the treatment of nail psoriasis.