Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Generalized pustular psoriasis: practical recommendations for Spanish primary care and emergency physicians.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory skin disease that can lead to life-threatening complications and require emergency medical treatment. Recurrent GPP flares are characterized by the sudden onset of widespread erythematous skin rash with sterile pustules, at times associated with fever, chills, general malaise, and other systemic inflammatory manifestations. Systemic complications such as cardiorespiratory failure, infections, and sepsis are potentially life-threatening and can result in an emergency department visit and/or hospitalization. Acute GPP episodes can be difficult to recognize and diagnose. The low incidence of the disease, its relapsing nature, the unpredictability of flare onset, and the lack of standardized diagnostic criteria are major obstacles to achieving rapid recognition and diagnosis in both the emergency department and the hospital setting.There is scarce evidence supporting the efficacy and safety of treatments commonly used for GPP; consequently, there is an unmet need for therapies that specifically target the condition. Our aim is to present a multidisciplinary approach to GPP to achieve a rapid diagnosis ensuring that the patient receives the most appropriate treatment for their pathology. The main recommendation for primary care and emergency physicians is to contact a dermatologist immediately for advice or to refer the patient when GPP or a flare is suspected.

Generalized pustular psoriasis (GPP) is a rare and serious skin disease that can cause life-threatening complications and require urgent medical treatment. When someone has a flare-up of GPP, their skin suddenly becomes red and covered with pus-filled bumps not caused by infection. They may also experience fever and chills and feel generally unwell. These flares can be very difficult to diagnose and lead to serious complications such as infections and organ failure, which may require a visit to the emergency department and/or admission to hospital. The diagnosis of GPP can be challenging as it is a rare and unpredictable disease with different types of flare-ups, making it difficult to identify in the emergency department and the hospital. This article shows that the best recommendation for primary care and emergency doctors is to improve their knowledge of this rare condition. Primary care and emergency doctors should immediately contact a dermatologist for advice or referral if they suspect that a patient has GPP or a flare-up of the disease. An approach involving doctors from different specialties can help ensure that patients receive the appropriate and timely care they need.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Drug survival and safety of biosimilars and originator adalimumab in the treatment of psoriasis: a multinational cohort study.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage. METHODS AND ANALYSIS: This study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes. ETHICS AND DISSEMINATION: The participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.

Tildrakizumab improves high burden skin symptoms, impaired sleep and quality of life of moderate-to-severe plaque psoriasis patients in conditions close to clinical practice.

BACKGROUND: Tildrakizumab (TIL) is an interleukin (IL)-23p19 inhibitor for the treatment of moderate-to-severe plaque psoriasis with long-term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed. OBJECTIVES: The TRIBUTE study (open-label, Phase IV) assessed the efficacy and impact on health-related quality of life (HRQoL) of TIL 100 mg in adult moderate-to-severe psoriasis patients (naïve to IL-23/Th17 pathway inhibitors) in conditions similar to clinical practice. METHODS: Key efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex-16. Additional patient-reported outcomes included Pain-, Pruritus- and Scaling-Numerical Rating Scale (NRS), Medical Outcome Study (MOS)-Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: One hundred and seventy-seven patients were enrolled (six patients did not complete the study). After 24 weeks, the proportion of patients achieving PASI scores ≤ 3, PASI 75, PASI 90 and DLQI 0/1 was 88.4%, 92.5%, 74.0% and 70.4%, respectively. Skindex-16 overall score improved (mean absolute change from baseline, MACB [95%CI]: -53.3 [-58.1, -48.5]). Significant benefits (MACB [95%CI]) were found on pruritus-, pain- and scaling-NRS scores (-5.7 [-6.1, -5.2], -3.5 [-4.1, -3.0] and -5.7 [-6.2, -5.2], respectively), MOS-Sleep (-10.4 [-13.3, -7.4] Sleep problems Index II) and WPAI (-36.4 [-42.6, -30.2] activity impairment, -28.2 [-34.7, -21.7] productivity loss, -27.0 [-32.9, -21.1] presenteeism and -6.8 [-12.1, -1.5] absenteeism). 82.7% of patients reported PBI ≥ 3 and the mean (SD) global TSQM score was high (80.5 [18.5]). Only one serious treatment-emergent adverse event was reported (not-related to TIL). CONCLUSIONS: TIL 100 mg treatment after 24 weeks in conditions close to real clinical practice showed a quick and high improvement in psoriasis signs and HRQoL. Patient reported improvements in sleep outcomes and work productivity, relevant benefits and high treatment satisfaction. The safety profile was favourable and consistent with Phase III trials.

Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study.

BACKGROUND: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. OBJECTIVES: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. METHODS: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. RESULTS: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. CONCLUSIONS: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

Generalized Pustular Psoriasis: A Review on Clinical Characteristics, Diagnosis, and Treatment.

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe inflammatory skin disorder characterized by sudden eruption of sterile pustules, often accompanied by systemic inflammation. GPP flares can be life-threatening if untreated, owing to potential serious complications such as sepsis and cardiovascular failure. Diagnosis and clinical measurement of disease severity in GPP are often difficult. Lack of standardized criteria in the international guidelines and the heterogeneity of cutaneous and extracutaneous symptoms make the diagnosis of GPP difficult. Clinical criteria for description and diagnosis of pustular conditions, including GPP, are variable and there is no specific agreement on commonly sustained concepts. Differentiation of GPP from other similar conditions/diseases is important and requires careful assessments. The evidence that supports current topical or systemic therapies is largely based on case reports and small studies. Some biologic agents that target key cytokines involved in the activation of inflammatory pathways have been used as treatments for GPP. Recently, spesolimab, an IL-36R antagonist, has been approved in the USA and Japan for the treatment of GPP flares in adults, but there are no currently approved treatments for GPP in Europe. The IL-36 pathway has recently emerged as a central axis driving the pathogenic inflammatory mechanisms of GPP. Biologic agents that inhibit the IL-36 pathway have shown efficacy and safety in patients with GPP, addressing a generally considered unmet medical need.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Secukinumab demonstrates efficacy, safety, and tolerability upon administration by 2 ml autoinjector in adult patients with plaque psoriasis: 52-week results from MATURE, a randomized, placebo-controlled trial.

Convenient administration is an important factor for treatment adherence in patients with psoriasis. MATURE study reports the efficacy, safety, tolerability, and pharmacokinetics (PKs) of secukinumab 300 mg 2 ml autoinjector (AI) from MATURE trial (NCT03589885). Eligible patients were randomized to secukinumab 300 mg 2 ml AI or 2× 1 ml prefilled syringe (PFS) or placebo. The co-primary endpoints were psoriasis area and severity index (PASI) 75 and investigator's global assessment (IGA) 0/1 response rates at Week 12 versus placebo. Other endpoints included PASI90/100 response, dermatology life quality index (DLQI) 0/1, PKs, 2 ml AI usability rated using self-injection assessment questionnaire (SIAQ), and safety. The study met both co-primary and secondary endpoints (p < 0.0001). Secukinumab 300 mg 2 ml AI and 2× 1 ml PFS treatments led to superior PASI75/90/100 (2 ml AI: 95.1%/75.6%/43.9%; 2× 1 mL PFS: 83.2%/62.6%/37.5% and placebo: 10%/5.0%/0.0%, respectively), IGA, and DLQI 0/1 responses compared with placebo, and efficacy was sustained through 52 weeks. SIAQ results showed high usability of self-injection with 2 mL AI device. No new safety signals were observed. Study design may bias the interpretation of safety profile after Week 12, due to different exposure of secukinumab versus placebo. Secukinumab 300 mg administered with the 2 mL AI demonstrated superior efficacy over placebo, good tolerability, and convenient administration.