Antinuclear antibodies may predict the development of immune-related adverse events in asymptomatic patients treated with immune checkpoint inhibitors: results from a single-center cohort.

We aim at investigating the association between subclinical autoimmunity and immune-related adverse events (irAEs) in a cohort of patients treated by immune checkpoint inhibitors for solid metastatic cancer. In the context of an oncology/rheumatology outpatient clinic, we evaluated patients treated with anti-PD-1 or anti-PD-L1. Before treatment, each patient underwent a physical evaluation and a blood sample to identify the presence of a set of autoantibodies. Indeed, all the patients were followed during treatment to identify irAEs and to assess the association with autoantibodies. Fifty-one patients (M/F 16/35; median age 70 years, IQR 16.5) were evaluated; 34.8% of patients showed ANA positivity, 6.5% ENA positivity (anti-SSA), 4.3% Ratest positivity, and 2.1% (one patient) ACPA positivity. During a median period of 21 months (IQR 38.75), 39.2% of patients developed irAEs. Musculo-skeletal manifestations, in particular arthritis, were the most frequent. We found a significant association between the positivity for ANA and the development of irAES (p = 0.03, RR 2.01, 95% CI 1.03-3.92). Furthermore, the progression-free survival was significantly longer in patients developing irAEs compared to those who are not experiencing these events (p = 0.007). This study underlines the potential role of ANA positivity as a predictive biomarker for the development of irAEs.

COVID-19 vaccination in cancer patients: Immune responses one year after the third dose.

Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an increased risk of developing severe COVID-19 compared to the general population. We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled. Binding and neutralizing antibody (Ab) titers were evaluated using chemiluminescence immunoassay (CLIA) and Plaque Reduction Neutralization Test (PRNT) respectively. T-cell response was analyzed using multiparametric flow cytometry. CPs who were administered three vaccine doses showed lower Ab titers than CPs with four doses and HDs. Overall, a lower cell-mediated response was found in CPs, with a predominance of monofunctional T-cells producing TNFα. Lower Ab titers and a weaker T-cell response were observed in CPs without prior SARS-CoV-2 infection when compared to those with a previous infection. While no differences in the humoral response were found comparing immunotherapy and non-immunotherapy patients, a stronger T-cell response in CPs treated with immunotherapy was observed. Our results emphasize the need of booster doses in cancer patients to achieve a level of protection similar to that observed in healthy donors and underlines the importance of considering the treatment received to reach a proper immune response.

Comparison of Long-Term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients.

BACKGROUND AND OBJECTIVES: Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients [Formula: see text] 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients. METHODS: A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit. RESULTS: A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively. Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52. CONCLUSIONS: This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.

An overview of new and emerging antibody therapies for moderate-severe atopic dermatitis in adults.

INTRODUCTION: A comprehensive review of the English-language medical literature was performed searching for ongoing and closed clinical trials concerning new and emerging monoclonal antibody therapies for moderate-to-severe atopic dermatitis in adults. AREAS COVERED: Atopic dermatitis is a chronic inflammatory cutaneous disease with a complex pathogenesis. In the last years, numerous advances in understanding the atopic dermatitis pathogenesis allowed to obtain several therapeutic options, such as numerous monoclonal antibodies. Some monoclonal antibodies, such as dupilumab (anti-IL-4 Rα) and tralokinumab (anti-IL13) are already approved for the treatment of moderate-to-severe atopic dermatitis, and numerous articles in the literature have demonstrated their efficacy and safety. As there are numerous drugs under investigation, this review focuses on emerging monoclonal antibody therapies. EXPERT OPINION: There are numerous monoclonal antibodies under investigation that may be approved in the near future for the treatment of atopic dermatitis. Data from phase 2b and phase III clinical trials in moderate-to-severe atopic dermatitis in adults indicate that these drugs have a promising efficacy and safety profile. Monoclonal antibodies currently under investigation will be available in the coming years to enrich the therapeutic choice of new alternatives that are valid both in terms of efficacy and safety.

A Rare Type of Radiation-Induced Alopecia: Proton-Induced Alopecia.

Introduction: Radiation-induced alopecia (RIA) is a side effect resulting from cranial radiation therapy (RT) and it can be temporary or permanent. In cancer patients, RIA is a less frequent event than chemotherapy-induced alopecia, although the former is more likely to cause permanent hair loss. It is characterized initially by intense anagen effluvium caused by acute dose-dependent damage to the matrix cells of anagen follicles. Proton therapy (PT) is a specific type of RT used in the treatment of brain tumors, which sometimes can cause proton-induced alopecia (PIA), a rare subtype of RIA. Below, we report a case of a patient who presented PIA following PT treatment of a meningioma of the frontal region. Case Presentation: A 38-year-old female patient presented to our trichology outpatient clinic for widespread hair loss in the frontal region. Following a diagnosis of meningioma of the frontal region 3 years ago, adjuvant radiotherapy treatment of the frontal region with scanning beam PT (mean dose of 45 Gy) was performed. Two weeks after the end of treatment, the patient came to our attention with diffuse hair loss at the level of the PT-treated area. Trichoscopy showed flame hairs, broken hairs, black dots, and pigtail hairs. A diagnosis of PIA was established, and topical treatment with minoxidil 5% solution twice a day was initiated. At the follow-up visit after 4 months, the patient had total hair regrowth. Conclusion: PIA is a subtype of RIA still poorly studied in the literature. Hair loss is caused by aggression by radiations of the hair follicle in the anagen phase, leading to an interruption of the mitotic activity of the matrix cells. The cells of the follicular bulb are characterized by marked mitotic activity at this stage and are consequently more susceptible to cytotoxic damage. All this causes tightening of the proximal portion of the hair shaft, increasing its fragility and susceptibility to breakage.

Psoriatic Alopecia and Paradoxical Psoriasis Induced by Adalimumab Successfully Treated with Certolizumab: Clinical, Trichoscopic, and in vivo Reflectance Confocal Microscopy Features.

Introduction: Psoriatic alopecia is considered a type of hair loss occurring in patients with psoriasis. Adalimumab is a fully humanized recombinant anti-TNF-alpha monoclonal antibody approved for treatment of psoriasis and psoriatic arthritis (PsA), rarely related to the occurrence of dermatological disorders. Case Presentation: We report the case of a 56-year-old female with PsA developing psoriatic alopecia and paradoxical psoriasis induced by adalimumab and successfully treated switching to certolizumab, evaluating response at both thrichoscopy and in vivo reflectance confocal microscopy. Discussion: Among anti-TNF-α agents, certolizumab is the least involved in the development of paradoxical reactions such as psoriatic alopecia and showed to be an effective and safe alternative therapeutic options to manage psoriasis and PsA minimizing the risk of paradoxical reactions.

The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

Rheumatic Diseases Development in Patients Treated by Anti-PD1 Immune Checkpoint Inhibitors: A Single-Centre Descriptive Study.

The introduction of the so-called immune checkpoint inhibitors (ICIs) substantially changed the history of cancer therapy. On the other hand, they can induce the development of rheumatic immune-related adverse events (Rh-irAEs). In the scenario of a joint oncology/rheumatology outpatient clinic, we conducted a single-centre descriptive study to define from a laboratory, clinical and therapeutic point of view, rheumatic conditions developed during anti-PD1 treatment. The study included 32 patients (M/F 16/16, median age 69, IQR 16.5). According to the international classification criteria, eight patients could be classified as affected by Rheumatoid Arthritis, one by Psoriatic Arthritis, six by Polymyalgia Rheumatica, five by systemic connective tissue diseases (two systemic lupus erythematosus, two Sjögren's syndrome, one undifferentiated connective tissue disease). The remaining patients were diagnosed as having undifferentiated arthritis or inflammatory arthralgia. The median interval between ICIs starting and the onset of symptoms was 14 weeks (IQR 19.75). Moving to treatment, the longitudinal observation revealed that all RA, PsA and CTD patients required the introduction of treatment with DMARDs. In conclusion, the growing use of ICIs in a real-life setting confirmed the possible development of different rheumatological conditions, further emphasising the need for shared oncology/rheumatology management.

Injections Site Reactions and Biologics for Psoriasis: A Questionnaire Based Real Life Study.

Background: Biologic selection for psoriasis treatment should take into account numerous factors including injection site reactions (ISRs) such as swelling at the injection site, pain, burning, erythema, all possibly reducing patient adherence. Methods: A 6-months observational real life study was performed involving psoriasis patients. Inclusion criteria were age ≥ 18 years, moderate-to-severe psoriasis diagnosis since at least 1 year, patients being on biologic treatment for psoriasis ≥ 6 months. A 14-item questionnaire was administered to all patients enrolled to assess whether the patient ever experienced ISRs after the injection of the biologic drug. Results: 234 patients were included: 32.5% received an anti-TNF-alpha drug, 9.4% received anti-IL12/23, 32.5% received an anti-IL17, 25.6% received an anti-IL23. 51.2% of study population reported at least one symptom related to ISR. 35.9% of patients experienced pain, 31.6% swelling, 28.2% burning sensation and 17.9% erythema. 3.4% of the surveyed population experienced anxiety or fear of the biologic injection due to ISRs symptoms. The greater incidence of pain was registered in anti-TNF-alpha and anti-IL17 groups (47.4% and 42.1%, p<0.01). Ixekizumab proved to be the drug with the highest rate of patients experiencing pain (72.2%), burning (77.7%) and swelling (83.3%). No patients reported biologics discontinuation or delay for ISRs symptoms. Conclusion: Our study highlighted that each different class of biologics for psoriasis was linked to ISRs. These events are more frequently reported with anti-TNF-alpha and anti-IL17.

How Adalimumab Impacts Antibiotic Prescriptions in Patients Affected by Hidradenitis Suppurativa: A 1-Year Prospective Study and Retrospective Analysis.

We conducted a one-year prospective study involving the enrollment of 58 patients with Hidradenitis Suppurativa. Through a retrospective analysis of data on the same patients, with reference to the year prior to the initiation of the anti-TNFα drug adalimumab, we aimed to show how the advent of this biologic therapy changes the number of days of antibiotic therapy, the number of flare-ups per year, and their duration in days, as well as the quality of life and perceived pain of patients.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part II: focus on elderly patients.

INTRODUCTION: The management of moderate-to-severe forms of psoriasis is becoming a frequent concern in geriatric age due to the higher risk to develop treatment adverse events, logistic issues, vulnerability to immune-related diseases and cancer, presence of comorbidities and the risk of drug interactions. In this context, traditional systemic treatments are often contraindicated, and biologic drugs and small molecules seem to be a valuable option. However, data on their effectiveness and safety in elderly patients are scant. AREAS COVERED: The aim of this review is to analyze the current literature in order to point out data on the efficacy and safety of biologic drugs and small molecules for the management of psoriasis in elderly patients in order to put the basis for universally shared treatment algorithm following available evidence. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review suggests biologics and small molecules as an effective and safe option for the management of moderate-to-severe forms of psoriasis in elderly patients.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part I: focus on pediatric patients.

INTRODUCTION: Psoriasis management is challenging, especially in pediatric age for different factors. The introduction of biologic drugs and oral small molecules (OSM) revolutionized the armamentarium of available weapons in psoriasis treatment. Despite the use of these drugs in adult patients has been widely investigated, pediatric patients have often been unconsidered in clinical trials and real-life studies. However, the high efficacy and speed of action, the safety profile and the ease-to-use administration make these innovative drugs an invaluable therapeutic opportunity. AREAS COVERED: The aim of this manuscript is to perform a review of the current literature examining data on the effectiveness and safety of biologic drugs and OSM for the management of psoriasis in pediatric patients in order to put the basis for universally shared treatment algorithm following available evidence. PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review based on currently available evidence suggests biologics and OSM as an ideal treatment option for pediatric patients, with an excellent profile in terms of efficacy and safety as compared to traditional systemic drugs.