The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

Adverse events of biological agents in pediatric rheumatologic diseases.

OBJECTIVES: To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs). METHODS: This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records. RESULTS: Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54-0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold (p = 0.024, 95% CI: 1.26-27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient. CONCLUSION: The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis.

Importance: Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown. Objective: To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema. Design, Setting, and Participants: This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022. Exposures: Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death. Main Outcomes and Measures: Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models. Results: Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78). Conclusions and Relevance: In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.

Safety Summary of Pediatric Inflammatory Bowel Disease Therapies.

Therapeutic options for the treatment of pediatric inflammatory bowel disease include aminosalicylates, enteral nutrition, corticosteroids, immunomodulators, biologics, and emerging small molecule agents. Infectious risk due to systemic immunosuppression should be mitigated by appropriate screening before therapy initiation. Rare but serious malignancies have been associated with thiopurine use alone and in combination with anti-tumor necrosis factor agents, often in the setting of a primary Epstein-Barr virus infection. Potential agent-specific adverse events such as cytopenias, hepatotoxicity, and nephrotoxicity warrant regular clinical and laboratory monitoring.

[Pay attention to the infectious complications in the clinical application of biological agents].

Biological agents have been widely used in the treatment of many clinical diseases by targeting specific immune cells or cytokines. In the course of clinical use, biological agents can lead to secondary immune deficiency, which increases the risk of infection. At present, there are no evidence-based guidelines or management opinions on the differences of infections caused by various biological agents, how to identify infectious complications in the course of treatment with different biological agents at an early stage, and how to take effective and targeted prevention. This paper summarizes the infection complications and their characteristics that need to be paid attention to in the clinical introduction of biological agents, aiming to help clinicians make reasonable decisions for infection complications in the process of using biological agents, reduce the incidence of infection, and improve the success rate of diagnosis and treatment.

Biologic Vs Conventional Therapies: Comparing Risk of Psoriasis-Associated Comorbidities.

Psoriasis is associated with multiple comorbidities. In this retrospective cohort analysis, we compared the comorbidities in patients who received biologic treatments with those who received conventional treatments. Our data indicates that biologics may be associated with lower rates of comorbidities in comparison to conventional therapy. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7119.

The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.

Biological Agent Switching in Patients With Juvenile Idiopathic Arthritis: A Tertiary Center Experience.

OBJECTIVE: The purpose of this study is to investigate the causes and outcomes of switching biological agents in juvenile idiopathic arthritis (JIA) patients using biological agents and compare the characteristics of patients whose biological agents are switched and those whose are not. METHODS: This medical records review study was conducted with 128 patients who were diagnosed with JIA at our clinic between January 2009 and January 2022 and were receiving biologic agents. Factors affecting the biologic agent switching were investigated. RESULTS: The JIA subtype with the most frequent switching in biological agents was systemic JIA (n = 13, 40.6%). Systemic JIA was followed by rheumatoid factor-negative polyarticular JIA and persistent oligoarticular JIA with 5 patients (15.6%), extended oligoarticular JIA and enthesitis-related JIA with 3 patients (9.3%), rheumatoid factor-positive polyarticular JIA with 2 patients (6.2%), and undifferentiated JIA with 1 patient (3.1%). Among the patients, 32 (25%) patients had their biological agent switched once, and 5 (3.9%) had theirs switched twice. The most frequently used biological agent was etanercept (n = 76, 59.3%), whereas the most frequently observed cases of biological agent switching were from an anti-TNF agent to another anti-TNF agent (40.6%). The reason for switching was unresponsiveness to the agent in 22 patients (68.8%), adverse effects in 6 patients (18.7%), drug intolerance in 1 patient (3.1%), and other reasons in 3 patients (9.3%). CONCLUSIONS: The most frequently used biological agent was etanercept; the most frequent cases of biological agents switching were from an anti-TNF agent to another anti-TNF agent.

[Psoriasis in children and adolescents : Short update and guideline-based treatment]. / Psoriasis im Kindes- und Jugendalter : Kurzes Update und leitliniengerechte Therapie.

Psoriasis is nowadays regarded as a multifactorial, inflammatory, immune-mediated systemic condition with predominant involvement of the skin. It starts in about one third of cases in childhood and adolescence and is often accompanied by marked impairment of the quality of life of sufferers and their parents. Aside from genetic disposition, trigger factors such as streptococcal infections are notably involved in manifestation and in exacerbations. The harmful role of comorbidities even in the young, particularly of obesity, has been well documented. Treatment options have considerably improved following the approval of five biologic agents in childhood but are still insufficiently used. The present article gives a short overview of current knowledge and the recommendations of the updated German guideline. Besides frequent types, unusual presentations such as pustular psoriasis, psoriasis dermatitis, and paradoxical psoriasis induced by tumor necrosis factor alpha (TNF-α) inhibitors are addressed.

Persistence of Biologics in the Treatment of Psoriatic Arthritis: Data From a Large Hospital-Based Longitudinal Cohort.

OBJECTIVE: To analyze the trends in biologics use at a specialized center over a period of 20 years. METHODS: We performed a retrospective analysis of 571 patients diagnosed with psoriatic arthritis enrolled in the Toronto cohort who initiated biologic therapy between January 1, 2000, and July 7, 2020. The probability of drug persistence over time was estimated nonparametrically. The time to discontinuation of first and second treatment was analyzed using Cox regression models, whereas a semiparametric failure time model with a gamma frailty was used to analyze the discontinuation of treatment over successive administrations of biologic therapy. RESULTS: The highest 3-year persistence probability was observed with certolizumab when used as first biologic treatment, while interleukin-17 inhibitors had the lowest probability. However, when used as second medication, certolizumab had the lowest drug survival even when accounting for selection bias. Depression and/or anxiety were associated with a higher rate of drug discontinuation due to all causes (relative risk [RR] 1.68, P = 0.01), while having higher education was associated with lower rates (RR 0.65, P = 0.03). In the analysis accommodating multiple courses of biologics, a higher tender joint count was associated with a higher rate of discontinuation due to all causes (RR 1.02, P = 0.01). Older age at the start of first treatment was associated with a higher rate of discontinuation due to side effects (RR 1.03, P = 0.01), while obesity had a protective role (RR 0.56, P = 0.05). CONCLUSION: Persistence in taking biologics depends on whether the biologic was used as first or second treatment. Depression and anxiety, higher tender joint count, and older age lead to drug discontinuation.

Incidence of severe infection in patients with rheumatoid arthritis taking biologic agents: a systematic review.

OBJECTIVE: The objective of this review was to estimate the population-based incidence and determine the types of severe infection and deaths experienced by patients with rheumatoid arthritis taking biologic agents. INTRODUCTION: Since the late 1990s, various biologic and synthetic drugs have been developed to treat rheumatoid arthritis. In recent years, the incidence of severe infection in patients with rheumatoid arthritis in Western nations has been determined by observational studies; however, no systematic review has been conducted on this topic. INCLUSION CRITERIA: The following inclusion criteria were considered: i) observational studies on patients with rheumatoid arthritis treated with biologic agents; ii) studies reporting the number of severe infections requiring hospitalization for treatment; iii) studies reporting person-years of observation data; and iv) studies based on rheumatoid arthritis registries, medical records from rheumatology centers, or insurance claim databases. METHODS: PubMed, CINAHL, Embase, and Web of Science were searched to identify published studies. The reference lists of all studies selected for critical appraisal were screened for additional studies. Unpublished studies were searched on MedNar and OpenGrey databases. All the searches were updated on December 6, 2021. After removing the duplicates, 2 independent reviewers screened titles and abstracts against the inclusion criteria and then assessed full texts against the criteria. Two reviewers independently appraised the study and outcome levels for methodological quality using the critical appraisal instrument for cohort studies from JBI. Two reviewers extracted the relevant information related to severe infection and drugs. RESULTS: Fifty-two studies from 21 countries reported severe infection rates associated with using 8 biologic agents, plus nonbiologic disease-modifying antirheumatic drugs. In total, 18,428 infections with 395,065 person-years of biologic drug exposure were included in the analysis. Thirty-five studies included infections in outpatients receiving intravenous antibiotic therapy. Fifteen studies reported the first episode of infection, and the remaining studies did not specify either the first or all of the episodes of infection. Inclusion of viral infection and/or opportunistic infection varied among studies. Fifteen studies reported the site of infection; respiratory, skin/soft tissue, urinary tract, and sepsis/bacteremia were commonly reported. Ten studies reported the case fatality rates, ranging from 2.5% to 22.2%. Meta-analysis was conducted for 8 biologic agents and conventional disease-modifying antirheumatic drugs. The infection rate varied from 0.9 to 18.1/100 person-years. The meta-analysis revealed an infection rate of 5.0/100 person-years (95% CI 3.8-6.7) among patients receiving tumor necrosis factor inhibitors (heterogeneity 98.2%). The meta-analysis for the other 3 biologic agents revealed a point estimate of 5.5 to 8.7/100 person-years with high heterogeneity. Sensitivity analysis indicated that registry-based studies were less likely to have very low or very high infection rates compared with other data sources. The definition of infection, the patient composition of the cohorts, and the type of databases appeared to be the primary sources of clinical and methodological heterogeneity. CONCLUSIONS: Due to high statistical heterogeneity, the meta-analysis was not suited to estimating a summary measure of the infection rate. Developing standardized data collection is necessary to compare infection rates across studies. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020175137.

[ANALYSIS OF DRUG-INDUCED ANAPHYLAXIS CASES USING THE JAPANESE ADVERSE DRUG EVENT REPORT DATABASE].

BACKGROUND: The epidemiology of drug-induced anaphylaxis (AN) using the Japanese nationwide database has not been reported, even though drugs are a common trigger of AN. OBJECTIVE: This study aimed to describe the epidemiological profile of drug-induced AN, including fatal cases, using the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-induced adverse events between April 2004 and February 2018 published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced AN and fatal cases was 1.03 cases/year per 100000 population and 0.03 cases/year, respectively. The most frequent causes of AN were diagnostic agents including X-ray contrast media (20.3%) and biological agents including human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotics (23.9%) were the most frequent causes. CONCLUSIONS: The frequency of drug-induced AN and fatalities in Japan remained unchanged over the 12-year period analyzed in this study. Diagnostic and biological agents were the most frequent causes of AN. Contrarily, fatalities were most frequently caused by diagnostic and antibiotic agents.

Safety of sequential biological therapy in inflammatory bowel disease: results from a tertiary referral centre.

BACKGROUND: Biologicals represent the cornerstone of treatment for moderate-to-severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events. AIM: To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals. METHODS: We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for. RESULTS: In total, 1575 patients were included with a median (interquartile range) follow-up of 10 (6-16) years and a duration of biological therapy of 71 (39-112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post-biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78-4.93], p < 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37-4.34], p = 0.002), female gender (1.25 [1.04-1.51], p = 0.02), and prior serious infections in the pre-biological setting (1.42 [1.03-1.96], p = 0.03). Malignancy rates were 1.06 per 100PY in the post-biological setting and increased with older age at biological initiation (1.04 [1.02-1.05], p < 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed. CONCLUSION: This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk.

The dark side of the moon: the immune-mediated adverse events of IL-17A/IL-17R inhibition.

As aberrant IL-17 signaling plays a critical role in the pathogenesis of psoriasis, biologic agents targeting this pathway have become an important weapon against this disease. Some biologic agents such as IL-17 inhibitors (secukinumab and ixekizumab) and the IL-17 receptor (IL17R) inhibitor (brodalumab) are relatively safe, tolerable and efficacious drugs. Nevertheless, side effects of IL-17 pathway inhibition occur. This review focuses on the dermatological manifestations linked to these treatments. Paradoxical psoriasis and atopic-like eczema may be the most common cutaneous adverse events, while manifestations such as neutrophilic dermatoses, hypersensitivity reactions, lichenoid eruptions, vasculitides, bullous diseases, lupus-like reactions, pigmentation disorders, adnexal diseases and granulomatous dermatoses have been described less frequently.

Comparative efficacy and safety of biologic agents in patients with active rheumatoid arthritis and inadequate response to tumor necrosis factor inhibitors: A Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to evaluate the relative efficacy and safety of biologic agents in patients with rheumatoid arthritis (RA) who show inadequate response to tumor necrosis factor (TNF) inhibitors. MATERIALS AND METHODS: A meta-analysis with the Bayesian network, combining direct and indirect randomized controlled trial (RCT) data, was conducted to examine the efficacy and safety of abatacept, rituximab, tocilizumab, sarilumab, sirukumab, and secukinumab in patients with RA who showed inadequate response to TNF inhibitors. RESULTS: 8 RCTs enrolling a total of 3,617 patients fulfilled the inclusion criteria. More significant American College of Rheumatology 20% (ACR20), ACR50, and ACR70 responses were obtained using therapies similar to these biologics than with placebo. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab was probably the best treatment for ACR20 response, followed by rituximab, abatacept, sarilumab, sirukumab, secukinumab 150 mg, secukinumab 75 mg, and placebo. Furthermore, identical distribution trends were observed for ACR50 response rates. In comparison, ACR70-based SUCRA rating revealed that rituximab, followed by tocilizumab, abatacept, sirukumab, secukinumab 150 mg, sarilumab, secukinumab 75 mg, and placebo might potentially result in ACR70. There was no significant difference between the number of adverse events and severe adverse events between the treatments. CONCLUSION: All biologic agents studied were effective in treating patients with TNF inhibitor-refractory RA; however, tocilizumab, rituximab, and abatacept appeared to be more efficient than sarilumab, sirukumab, and secukinumab. There were no differences between the treatments with respect to safety.

Current treatment of recurrent pericarditis: safety considerations and future directions.

INTRODUCTION: Recurrent pericarditis is one of the most troublesome complications of pericarditis affecting a substantial amount of patients and often severely impairing the quality of life. Current medical treatments range from non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids to biological agents (anti IL-1 agents, especially anakinra and rilonacept), intravenous immunoglobulins and immunosuppressive treatments. Safety is a major issue to deal with since the disease often affects relatively young or middle-aged patients. AREAS COVERED: The review is aimed at providing an update on the efficacy and safety of current medical therapies for recurrent pericarditis including most recent advances represented by anti IL-1 agents. EXPERT OPINION: Therapy of recurrent pericarditis has evolved over years leading to a more evidence-based and personalized treatment based on clinical presentation and pathophysiology. The main distinction is between patients with an inflammatory phenotype (e.g. fever, elevation of markers of inflammation, pericardial, and/or pleural effusion) vs. those without an inflammatory phenotype. Colchicine and anti IL-1 agents are especially efficacious and indicated for those with an inflammatory phenotype, while corticosteroids, azathioprine, and immunoglobulins seem more indicated for those without evidence of systemic inflammation.

Paradoxical Reactions to Biologicals in Chronic Inflammatory Systemic Diseases.

BACKGROUND: Biological agents that contain substances affecting the immune system are increasingly being used to treat chronic inflammatory systemic diseases. Aside from the expected adverse effects, they can also induce unexpected paradoxical reactions (PR). A reaction is called paradoxical when a substance that is generally therapeutically effective induces the opposite of what is intended, with the new appearance or exacerbation of inflammatory changes in the skin and other organs. METHODS: The paradoxical reactions that have been described since 1997 are presented here on the basis of the available literature on the main types of chronic inflammatory systemic disease, which was retrieved by a selective search in the PubMed and Google Scholar databases. RESULTS: Many studies and registers to date contain no mention of paradoxical reactions. Anti-TNF-alpha treatment for patients with ankylosing spondylitis leads to paradoxical reactions in 19 per 1000 patient years, compared to 11 per 1000 patient years with conventional treatment; the corresponding frequency for paradoxical psoriasis in patients with other chronic inflammatory systemic diseases are 1.04-3.68 versus 1.45 per 1000 patient years. Paradoxical reactions tend to be more common with anti-TNF-alpha treatment than, for example, with the administration of ustekinumab, vedolizumab, and other agents. It is unclear whether some drugs have been noted to cause PR more commonly than others because of varying times since their approval, differences in immunogenicity, and differences between their target structures. CONCLUSION: Paradoxical reactions induced by biological agents are a problem confronting physicians in multiple specialties. They need to be distinguished from infectious and neoplastic diseases and from autoimmune conditions of other types. The treatment options for paradoxical reactions include local treatment, symptomatic therapy, prednisolone administration, and the discontinuation or switching of the biological agent, although some patients will react with a further paradoxical reaction to a different biological agent that is used instead.

Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis: A systematic review and meta-analysis.

BACKGROUND: Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common. OBJECTIVE: To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy. DATA SOURCES: A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment. STUDY ELIGIBILITY CRITERIA: The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0). RESULTS: The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18-1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02-1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11-2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31-4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07-2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64-2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89-5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20-10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22-11.34; I2 = 0%) did not. LIMITATIONS: Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202110027.

Prevalence of HPV genital infection in patients with moderate-to-severe psoriasis undergoing systemic treatment with immunosuppressive agents or biologics.

Psoriasis is an immune-mediated inflammatory disease and its relationship with infection has been extensively investigated. Concern for the increased prevalence of human papilloma virus (HPV) infection in patients undergoing systemic immunomodulatory or immunosuppressive therapies for psoriasis has been gradually growing among clinicians. To evaluate the prevalence of HPV in a cohort of patients with psoriasis treated with currently available systemic, conventional and biotechnological drugs. A multi-centric prospective study was conducted in the main dermatological clinical centres of central and southern Italy. Data from 588 patients (366 males and 222 females) with moderate-to-severe psoriasis, aged ≥18 years and treated with conventional and biological drugs, were collected based on a documented history of HPV infection, a positive Papanicolaou test (Pap-test) when available, and clinical evidence of genital warts reported during consultation. Overall, 18 of 588 patients (3.6% [95% CI: 1.8-4.5]) were positive for HPV or had a history of cervical cancer. Considering anamnestic and demographic data, such as gender, age, smoking, weight and body mass index, no statistically significant differences between HPV+ and HPV- patients were found. Moreover, the eradication of HPV infection was successfully achieved using conventional treatments. The prevalence of HPV infection in patients with moderate-to-severe psoriasis, undergoing systemic treatment with immunosuppressive agents or biologics, appears to be the same as that in the general Italian population, indicating that the level of infection among such patients is acceptable.