Dupilumab, a monoclonal antibody targeting interleukin-4 antibody, is approved for use in many type 2 inflammatory diseases, including atopic dermatitis. It is generally well tolerated with no need ...of routine laboratory monitoring. However, several adverse events have been reported during real-world practice and in pivotal trials. We conducted a systematic literature research of the PubMed, Medline, and Embase databases to identify articles recording the clinical manifestation and potential pathogenesis of these adverse events with interests (AEIs) to dermatologists. In total, 547 cases from 134 studies have developed 39 AEIs 1 day to 2.5 years after dupilumab treatment. The most common AEIs are facial and neck dermatitis (299 cases), psoriasis (70 cases), arthralgia (56 cases), alopecia (21 cases), cutaneous T cell lymphoma (19 cases), severe ocular diseases (19 cases), and drug eruption (6 cases). Most of the AEIs recorded in this review resolved or improved after dupilumab discontinuation or the addition of another treatment, whereas 3 of the cases died of severe AEI. The potential pathogenesis included T help type 1 (Th1)/T help type 2 (Th2) imbalance, Th2/T help type 17 (Th17) imbalance, immune reconstitution, hypersensitivity reaction, transient hypereosinophilia related, and Th1 suppression. Clinicians should be alert of these AEIs for timely diagnosis and appropriate treatment.
Advances of biologic agents have changed the treatment paradigm of psoriasis to higher efficacy and better quality of life. However, the demand for biologic switch is increasing due to patient's ...greater expectation and decreasing efficacy in long-term use. Also, biologic-induced adverse effects necessitate the switching of biologics.
This review article was divided into two parts. The first part focused on the biologic switch due to lack of efficacy. The second part provided switching suggestions related to adverse effects.
Biologic switch in psoriasis was mainly due to lack of efficacy, and the subsequent biologic agent was usually given at the next scheduled time point without washout period. In pivotal randomized controlled trials, patients with poor response to TNF-alpha inhibitors and ustekinumab achieved better efficacy after switching to IL-23 and IL-17 inhibitors. In addition, real-world data showed that intra-class switch could still achieve a 50%-80% of PASI 75 response in individuals with anti-IL-17 failure histories. As for the biologic switch due to adverse effects, washout period was recommended and transition to a biologic agent with different modes of action was preferred, especially class-specific adverse events.
Impetigo herpetiformis (IH) is a rare form of pustular psoriasis which may result in maternal and fetal morbidity and even mortality. Deficiency of interleukin-36 receptor antagonist (DITRA) is the ...most frequently identified genetic defect of IH. Currently there are no biologics approved for IH despite the revolutionary role of biologics in the treatment of plaque and pustular psoriasis. Anecdotal reports of biologics use in DITRA patients with IH are also limited.
We present herein a case series of 6 Chinese IH patients harboring IL36RN gene c.115+6T>C mutation during 8 pregnancies, treated with various biologics, including adalimumab, etanercept and secukinumab.
Most pregnancy courses were uneventful, except for one woman who had recurrent episodes of decreased fetal heart rate variability after adalimumab injections, which subsided after switching to etanercept. The treatment effectiveness and safety demonstrated in our cases suggested the role of biologics for the treatment of IH in patients with DITRA.
In 2022, U.S. Food and Drug Administration (FDA) approved the first biologics, intravenous spesolimab, for acute flare of generalized pustular psoriasis (GPP). The drug works by blocking IL-36 ...signaling, the key pathway of GPP. Among the known mutations causing GPP,
mutations are most common, and the presence of
mutations had been found to affect the clinical manifestations and treatment response of GPP.
Literature search was conducted in PubMed, Embase and ClinicalTrials.gov for relevant studies discussing biologic treatment for GPP with special emphasis on larger studies, pediatric group, pregnant women, and the influence of
mutation on the effectiveness of biologics.
The approval of spesolimab for GPP flare treatment marks a new era. However, whether spesolimab will be placed as the treatment of choice remains unknown, considering its higher cost, lack of direct comparison with existing biologics, and uncertain effects on co-existing plaque-type psoriasis. However, the demonstration of numerically better efficacy for patients carrying pathogenic
mutations suggests the role of pharmacogenetics in the choices of GPP treatment. Future randomized studies are warranted to investigate the effectiveness and safety of biologics for GPP in pediatric and pregnant groups.
Guselkumab effectively treats moderate-to-severe psoriasis.
To evaluate the cumulative safety experience of guselkumab using pooled data from the VOYAGE 1 and 2 studies through 5 years.
Patients were ...randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-to-guselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264.
Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed.
No direct treatment comparisons were possible after week 52.
The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis.
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Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus ...(HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.
IntroductionGeneralized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite ...the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.Methods and analysisAt least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.Ethics and disseminationThe study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation’s Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.Trial registration detailsClinicalTrials.gov identifier: NCT03782792; Pre-results.
•Pemphigus is a fatal blistering disease and causes significant impairments in quality of life of patients.•However, there are limited informations on the trends in disease burden of pemphigus in ...Asian populations.•Despite a stable mortality rate, there are recent declines in the medical utilization and expenditure for pemphigus in Taiwan, reflecting better disease control. Nevertheless, we need to investigate strategies to reduce the persistently elevated mortality.
Data on trends in epidemiological characteristics and economic burden of pemphigus are scarce.
To describe national trends in pemphigus’ incidence, mortality, hospitalizations, and expenditures between 2003 and 2015 in Taiwan.
This nationwide study used the Taiwan National Health Insurance Research Database to identify pemphigus patients from 2003 to 2015. Annual incidence, prevalence, healthcare utilization, and expenditure trends were calculated and analyzed.
Pemphigus’ incidence increased significantly from 3.19 to 4.70 per million person-years in 2003–2010 but fluctuated in 2011−2015. Pemphigus patients had higher mortality and care costs. Medical utilization and expenditure declined for pemphigus inpatients and outpatients. Systemic corticosteroid use decreased, but mortality remained stable.
The health expense reduction for pemphigus was mainly attributed to decreased utilization, length of stay, and inpatient costs. The persistently elevated mortality rate highlights an unmet need in pemphigus therapy.
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