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.     

Secukinumab in moderate-to-severe plaque psoriasis: a multi-center,retrospective, real-life study up to 52 weeks observation

Objectives: To evaluate efficacy and safety of the anti-IL-17 drug secukinumab in a real-life large cohort of patients with moderate-to-severe plaque psoriasis in Central Italy.

Methods: Multicenter, retrospective study with an observation period of up to 52 weeks. Efficacy was assessed by Psoriasis Area and Severity Index (PASI) score; clinical and laboratory examinations were performed at baseline and at weeks 4, 12, 24, 36, and 52.

Results: A 90% and a 100% PASI score reduction (PASI90 and PASI100) were reported in 67.5% and 55% of patients at week 12, respectively. A rapid improvement of skin lesions was observed particularly in young patients and in patients naïve to biologics: at week 4, the achievement of PASI90 and PASI100 was higher in younger patients (odds ratio [OR] 0.95, and 0.95; p = 0.003, and 0.005, respectively); PASI90 was achieved by 42.0% of patients naïve to biologics and by 17.0% of patients with prior exposure to biologics (PBT) (OR 0.24; p = 0.001); and PASI100 was reached by 25.5% of naïve patients and 9.8% of PBT (OR 0.28; p = 0.015).The drug was well tolerated.

Conclusion: Secukinumab was effective in this real-life analysis, with rapid clinical improvement and long-term maintenance of results.     

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.     

Rationale and early clinical data on IL-17 blockade in psoriasis

Psoriasis vulgaris is a chronic, immune-mediated, inflammatory disease that affects between 2 and 3% of the US population. Often severely physically and emotionally debilitating, psoriasis has driven investigators to strive to better characterize its complex immune pathogenesis. Some of the most promising and exciting advances have occurred in the last decade with recognition of the IL-23/Th17 pathway in disease initiation, progression and maintenance. Biologic therapies targeting various points in the pathway have met with success, prompting the study of the safety and efficacy of IL-17 blockade for moderate-to-severe plaque psoriasis. This article will review the rationale and early clinical data on IL-17 blockade in psoriasis.     

Long‐term efficacy and safety of secukinumab in Japanese patients with moderate to severe plaque psoriasis: 3‐year results of a double‐blind extension study

Secukinumab, a fully human monoclonal antibody neutralizing interleukin‐17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long‐term (3‐year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI‐75) response at week 12 were re‐randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52‐week core study, and 47 patients entered the extension study with the same double‐blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI‐90 and ‐100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two‐thirds of 300 mg FI patients, and all EuroQoL 5‐Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified.     

Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis

Many pediatric psoriasis patients suffer from nail involvement and psoriatic arthritis. In adults, biologic agents have demonstrated success in treating refractory nail psoriasis and arthritis, but studies are limited in children. In this report, we present a pediatric patient with severe, recalcitrant nail and joint psoriasis, successfully treated with secukinumab.     

Evidence that a neutrophil–keratinocyte crosstalk is an early target of IL‐17A inhibition in psoriasis

The response of psoriasis to antibodies targeting the interleukin (IL)‐23/IL‐17A pathway suggests a prominent role of T‐helper type‐17 (Th17) cells in this disease. We examined the clinical and immunological response patterns of 100 subjects with moderate‐to‐severe psoriasis receiving 3 different intravenous dosing regimens of the anti‐IL‐17A antibody secukinumab (1 × 3 mg/kg or 1 × 10 mg/kg on Day 1, or 3 × 10 mg/kg on Days 1, 15 and 29) or placebo in a phase 2 trial. Baseline biopsies revealed typical features of active psoriasis, including epidermal accumulation of neutrophils and formation of microabscesses in >60% of cases. Neutrophils were the numerically largest fraction of infiltrating cells containing IL‐17 and may store the cytokine preformed, as IL‐17A mRNA was not detectable in neutrophils isolated from active plaques. Significant clinical responses to secukinumab were observed 2 weeks after a single infusion, associated with extensive clearance of cutaneous neutrophils parallel to the normalization of keratinocyte abnormalities and reduction of IL‐17‐inducible neutrophil chemoattractants (e.g. CXCL1, CXCL8); effects on numbers of T cells and CD11c‐positive dendritic cells were more delayed. Histological and immunological improvements were generally dose dependent and not observed in the placebo group. In the lowest‐dose group, a recurrence of neutrophils was seen in some subjects at Week 12; these subjects relapsed faster than those without microabscesses. Our findings are indicative of a neutrophil–keratinocyte axis in psoriasis that may involve neutrophil‐derived IL‐17 and is an early target of IL‐17A‐directed therapies such as secukinumab.     

Real world data from the use of secukinumab in the treatment of moderate‐to‐severe psoriasis,including scalp and palmoplantar psoriasis: A 104‐week clinical study

Several clinical studies demonstrated the safety and efficacy of the interleukin‐17 inhibitor secukinumab in the systemic treatment of moderate‐to‐severe psoriasis, as well as psoriatic arthritis (PsA) in adults, whereas real‐world data is limited. A single‐center clinical study was performed to evaluate in real‐world practice the efficacy of secukinumab up to Week 104 of treatment in moderate‐to‐severe chronic plaque psoriasis, including scalp and palmoplantar involvement, according to Physician Global Assessment (PGA), PASI75/90/100 and scalp, and palmoplantar PGA. Drug survival, the safety profile of secukinumab, and patient's quality of life were also assessed during a 2‐year observation period. Out of 83 patients included, 56.3% were biologic‐naïve, and 94% had scalp, 25.3% palmoplantar, and 43.9% joint involvement. At Week 16, PASI75/PASI90/PASI100 were observed in 83.8/70.0/46.3%, respectively. Scalp and palmoplantar PGA were rapidly improved, with 98.7 and 95.5%, respectively, reaching clear/almost clear skin at Week 16. After 104 weeks, drug survival was 74.5%. A significant improvement of the quality of life was observed. Biologic‐naïve patients without coexisting PsA benefited the most. Real‐world data demonstrated secukinumab efficacious in chronic plaque psoriasis, including specific locations such as scalp and palmoplantar psoriasis with a safety profile similar to that in clinical trials.