Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

BACKGROUND: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab). METHODS: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. RESULTS: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 µg/mL [P = .49]; adalimumab: 11.1 vs 10.5 µg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 µg/mL [P < .01]; adalimumab: 9.1 vs 12.3 µg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). CONCLUSIONS: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

For children with Crohn's disease treated with biologic medications, with and without low-dose methotrexate, the role of drug levels on treatment failure in a recent prospective trial is unclear. These data suggest patients on infliximab with therapeutic drug levels are more likely to continue any therapy, and the effect on patients treated with adalimumab requires more investigation.

Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience.

BACKGROUND: Type 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist. METHODS: This is a Canadian multicenter retrospective study of real-world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics. RESULTS: Note that 225 consecutive patients were included. Thirty-six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p-value < 0.001). CONCLUSIONS: Switching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.

Factors Affecting Treatment Persistence in Japanese Patients with Psoriasis Prescribed Biologics: A Real-World Study Using an Insurance Claim Database.

INTRODUCTION: Poor persistence to biologics can result in suboptimal health outcomes and increased economic burden for chronic conditions, including psoriasis (PsO). In Japan, studies evaluating factors responsible for biologic treatment persistence in patients with PsO are limited. We assessed biologic treatment persistence (median treatment duration and overall treatment survival) and associated factors in patients with PsO in a real-world setting. METHODS: This retrospective analysis of insurance claims records from the Japan Medical Data Center (JMDC) database included patients with PsO [International Classification of Diseases (ICD) code: L40.x] ≥ 18 years of age who had received biologic treatment. Treatment persistence was analyzed using data from 2016 to 2020 by biologic class and by individual biologics (infliximab, adalimumab, ustekinumab, guselkumab, secukinumab, ixekizumab, and brodalumab) in bio-naïve (who initiate first biologic at index) and bio-experienced patients. Kaplan-Meier survival (treatment persistence), and multivariate Cox proportional hazard regression (predictive factors) analyses were used. RESULTS: Overall, 1528 patients with PsO were included (mean age 47.4 years). Infliximab had the longest median treatment duration (33.6 months), while brodalumab had the shortest (9.7 months) among biologics evaluated. Of the biologics evaluated, 1-year treatment survival was highest with guselkumab (83%), and lowest with brodalumab (45%). Bio-experienced patients showed slightly longer median treatment duration than bio-naïve patients (22.8 versus 18.1 months). Factors predictive of treatment persistence were sex [male; hazard ratio (HR) 0.84, p = 0.016] and specific PsO diagnostic codes, such as L40.0 (PsO vulgaris; HR 0.69; p = 0.006), L40.1 (generalized pustular PsO; HR 0.75; p = 0.034), and L40.9 (PsO unspecified; HR 0.72; p = 0.001). Meanwhile, age and Charlson Comorbidity Index score were significantly associated with adalimumab and infliximab treatment persistence, respectively. CONCLUSION: Among biologics evaluated, infliximab had the longest median treatment duration, and guselkumab had the highest 1-year treatment survival. Sex and specific PsO diagnostic codes influenced overall treatment persistence. These findings could inform long-term treatment plans for PsO in real-world clinical settings.

Prescribed cumulative dosage of corticosteroids to patients with inflammatory bowel disease diagnosed between 2006 and 2020: a retrospective observational study.

Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s. Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018. Design: Retrospective observational study. Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD (n = 386) at our clinic for those diagnosed between 2006 and 2018. Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1-5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = -0.164, p = 001), but had increased for budesonide (rs = 0.202, p < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = -201, p = 0.012). Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level.

The use of steroids in patients with inflammatory bowel disease diagnosed between 2006 and 2020 In the 1950s, corticosteroids and immunomodulators were introduced, and in combination with improved surgery, the mortality rates dramatically decreased in patients with inflammatory bowel disease (IBD) Although corticosteroids are effective in the short term they have no proven efficacy in long-term therapy for IBD, and owing to the risk of side effects, their long-term use should be restricted. Based on the evolution of treatments and treatment strategies for IBD in the 2000s, we aimed to study to the extent to which corticosteroids have been used in the first five years after diagnosis for patients with IBD diagnosed at our clinic between 2006 and 2020. To what extent is prednisolone prescribed in the first five years after diagnosis? Has the pattern of corticosteroid prescription changed after the introduction of advanced therapy and biosimilars to TNF inhibitors? We found that the proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year one to five after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1g in the first five years after diagnosis was 40.1% for ulcerative colitis (UC) and 34.9% for Crohns disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined but increased for budesonide between 2006-2020. The prescription of any immunomodulator for IBD in the first five years from diagnosis was stable between the years 2006-2018, but there was a minor increase in the prescription of TNF-inhibitors. The use of 5-ASA decreased in patients with CD. We conclude that there was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains on relatively high level.

Screening and identification of Paenibacillus polymyxa GRY-11 and its biological control potential against apple replant disease.

Apple replant disease (ARD) is a significant factor restricting the healthy development of the apple industry. Biological control is an important and sustainable method for mitigating ARD. In this study, a strain of Paenibacillus polymyxa GRY-11 was isolated and screened from the rhizosphere soil of healthy apple trees in old apple orchards in Shandong Province, China, and the effects of strain GRY-11 on soil microbial community and ARD were studied. The result showed that P. polymyxa GRY-11 could effectively inhibit the growth of the main pathogenic fungi that caused ARD, and the inhibition rates of the strain against Fusarium moniliforme, Fusarium proliferatum, Fusarium solani, and Fusarium oxysporum were 80.00%, 71.60%, 75.00%, and 70.00%, respectively. In addition, the fermentation supernatant played an active role in suppressing the growth of pathogenic fungi. The results of the pot experiment showed that the bacterial fertilizer of the GRY-11 promoted the growth of Malus hupehensis seedlings, improved the activity of protective enzymes in plant roots, enhanced the soil enzyme content, and optimized the soil microbial environment. In general, the GRY-11 can be used as an effective microbial preparation to alleviate ARD. Our study offers novel perspectives for the prevention of ARD.

[Efficacy of biologics for severe asthma on allergic comorbidities]. / Efficacité des biothérapies de l'asthme sévère sur les comorbidités allergiques.

Identification of therapeutic targets other than asthma can guide the choice of biologics in cases of severe asthma. Some of the allergic diseases (atopic dermatitis, food allergies, allergic rhinoconjunctivitis) that may be associated with asthma can be treated with biologics. In this review, we aim to assess the effectiveness of these biologic therapies on the allergic comorbidities of asthma. In the treatment of atopic dermatitis, only Dupilumab, an anti-IL4Rα, has proven its effectiveness and has received reimbursement authorization for this indication. In patients presenting with allergic rhinoconjunctivitis, Omalizumab has shown effectiveness, but has not been approved for this indication. Data from post-hoc analyses of studies on severe asthma likewise suggest the effectiveness of Dupilumab regarding allergic rhinitis. While these two biologic therapies have shown positive signals, inducing oral food tolerance, the relevant data are not robust. Biologic therapies targeting IL-5 or its receptor (Mepolizumab, Benralizumab) have seldom been evaluated in allergic comorbidities, excepting atopic dermatitis, for which their effectiveness has not been proven. Lastly, there are interesting data on the combination of biologic therapy and allergen immunotherapy in cases of allergic rhinitis and food allergies, but they need to be confirmed by randomized studies.

Recent Advances in Allergic Rhinitis: A Narrative Review.

Allergic rhinitis (AR) is a prevalent chronic respiratory condition characterized by nasal inflammation, sneezing, congestion, and itching, significantly impacting quality of life. Over recent years, considerable advancements have been made in understanding the pathophysiology, diagnosis, and management of AR. This narrative review aims to synthesize these recent developments, providing a comprehensive overview of key areas. Emerging insights into AR pathophysiology have elucidated the complex interplay between genetic predisposition, environmental factors, and immune system dysregulation. Notably, the role of the epithelial barrier and the microbiome in AR pathogenesis has garnered increasing attention, offering potential targets for novel therapies. Advances in diagnostic technologies, such as component-resolved diagnostics and molecular allergology, have enhanced the precision of allergy identification, enabling more personalized treatment approaches. In terms of management, significant progress has been made in pharmacological and non-pharmacological treatments. Novel biologics targeting specific pathways involved in AR, including monoclonal antibodies against immunoglobulin (Ig)E and interleukin (IL)-4/13, have shown promise in reducing symptoms in refractory cases. Additionally, there has been a resurgence in interest in non-pharmacological strategies, including allergen avoidance, immunotherapy, and complementary therapies, which offer holistic options for patient care. The integration of digital health tools and mobile applications in AR management has further empowered patients, allowing for real-time symptom tracking and personalized treatment adjustments. Recent guidelines emphasize a multidisciplinary approach to AR management, promoting integrated care models that involve collaboration between allergists, primary care providers, and other specialists. These guidelines also highlight the importance of patient-centered care, advocating for shared decision-making and tailored treatment plans based on individual patient profiles. In conclusion, the landscape of allergic rhinitis management is rapidly evolving, with ongoing research and innovation paving the way for improved outcomes. This review underscores the importance of staying abreast of these advances to optimize the care and quality of life for individuals affected by allergic rhinitis.

Practice Patterns of Biologics Prescriptions and Surgery in Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging to manage effectively, with high symptom recurrence rates and significant impacts on quality of life, prompting a need to evaluate the real-world use of biologics and optimize treatment strategies. OBJECTIVE: To assess the real-world application and perspectives of American Rhinologic Society (ARS) members on biologic treatments and surgical interventions for CRSwNP, focusing on clinical practice patterns, adoption of biologics, and their impact on surgical practices. METHODS: A standardized questionnaire evaluated clinical practice patterns of biologics prescriptions and surgery in treating CRSwNP between July 2022 and August 2023. Data collected from 162 ARS members were analyzed. RESULTS: Of 162 participants, a substantial majority (95.06%, n = 154) reported prescribing biologics in their practice. Notably, 45.45% (n = 70) found biologics easily accessible, although accessibility challenges remained for some. The impact of biologics on surgical practices was significant, with 36.36% (n = 56) observing a marked reduction in revision sinus surgeries. Among the participants, 47.16% (n = 71) agreed that aspirin-exacerbated respiratory disease (AERD) was the highest phenotype that tended to increase the possibility of biological treatment by more than 20%. Adopting Patient-Reported Outcome Measures (PROMs) was prevalent, with 57.79% (n = 89) utilizing them in patient management. CONCLUSION: The study highlights the evolving landscape in managing CRSwNP, with a marked trend toward integrating biological treatments into clinical practice. It underscores the necessity for continued research, updates to clinical guidelines, and enhanced practitioner education to optimize treatment outcomes for CRSwNP patients.

Infection risk with JAK inhibitors in dermatoses: a meta-analysis.

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo-controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta-analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta-analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61-1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32-1.31, P = 0.23). The incidence of varicella-zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08-2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93-2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13-2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella-zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short-term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections.

Infection and infestation-related adverse events of biologics in psoriasis: insights from the Food and Drug Administration Adverse Event Reporting System (FAERS).

OBJECTIVE: The study aims to thoroughly assess the adverse events related to infections and infestations associated with biological agents used for psoriasis using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database. METHODS: We analyzed FAERS data from the first quarter of 2004 to the fourth quarter of 2023. The study included TNF-α inhibitors (etanercept, infliximab, adalimumab), IL-12/23 inhibitors (ustekinumab), IL-23p19 inhibitors (guselkumab), and IL-17 inhibitors (secukinumab, ixekizumab). We used disproportionality analysis and Bayesian methods to quantify the related adverse event (AE) signals. RESULTS: Most AEs related to infections and infestations are already listed on the drug packaging labels. Notably, TNF-α inhibitors are associated with a significantly higher incidence of tuberculosis-related diseases compared to other biological agents. In contrast, IL-17 inhibitors show a greater variety and number of fungal infection-related AEs than their counterparts. Furthermore, our study has identified new potential AEs that require the attention of clinicians. CONCLUSION: In clinical practice, it is advisable to monitor the risks of infections and infestations in patients receiving biological agents for psoriasis to enable early detection and intervention. Our findings highlight the need for further epidemiological investigations to establish causality and guide clinical practice in managing these risks effectively.

Dynamics of biological markets with multiple biosimilar competitors in the United States.

BACKGROUND: The dynamics of biological markets with multiple biosimilar competitors in the United States are poorly understood. Moreover, due to confidentiality issues, the relationship between originator biologic net prices, rebates, and biosimilar entry is largely unexplored. RESEARCH DESIGN AND METHODS: We conducted a review of the Food Drug Administration (FDA) purple book and manufacturer websites to identify all originator biologics with multiple competitors and their characteristics. We leveraged a novel data source to examine originator biologic net prices and rebates over time and used descriptive statistics and interrupted time-series analyses to assess their relationship with biosimilar entry. RESULTS: By December 2022, only five originator biologics had three or more available biosimilar competitors. Mean time between biosimilar approval and biosimilar launch was 9 months (SD = 7.04 months). By third biosimilar competitor, entry net prices for originator biologics had decreased by 9.34% to 50.93%, while rebates had increased by 25.35% to 89.71%. CONCLUSIONS: Very few originator biologics have multiple available biosimilar competitors. Barrier to biosimilar availability seems to be at the approval level as the time between approval and launch is relatively short. However, originator biologics respond quickly to biosimilar competition, mainly through an increase in rebates.

Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.

The evolving development landscape of biotherapeutics and their growing complexity from simple antibodies into bi- and multi-specific molecules necessitates sophisticated discovery and engineering platforms. This review focuses on mammalian display technology as a potential solution to the pressing challenges in biotherapeutic development. We provide a comparative analysis with established methodologies, highlighting key aspects of mammalian display technology, including genetic engineering, construction of display libraries, and its pivotal role in hit selection and/or developability engineering. The review delves into the mechanisms underpinning developability-driven selection via mammalian display and their broader implications. Applications beyond antibody discovery are also explored, alongside advancements towards function-first screening technologies, precision genome engineering and AI/ML-enhanced libraries, situating them in the context of mammalian display. Overall, the review provides a comprehensive overview of the current mammalian display technology landscape, underscores the expansive potential of the technology for biotherapeutic development, addresses the critical challenges for the full realisation of this potential, and examines advances in related disciplines that might impact the future application of mammalian display technologies.

Patients' Preferences Regarding Modes of Systemic Psoriasis Treatment - A Qualitative Study.

Background: Treatment with pathogenesis-directed biologics and oral systemic drugs have made complete clearance of psoriasis a realistic expectation for many patients with psoriasis. Patients' preferences among these treatments varies. Objective: To understand factors impacting psoriasis patients'preferences for injection vs oral medication. Methods: Psoriasis patients who receive systemic psoriasis treatment were asked to participate in a semi-structured interview. Sample size was based on achieving saturation with equal number of patients preferring oral vs injectable medications to ensure equal representation of both groups. Qualitative analysis was performed to interpret the results. Results: Twenty-two patients participated in the study, 12 males and 10 females. Ten patients were receiving oral medication (apremilast or methotrexate) and 12 patients were receiving injectables (guselkumab, adalimumab, risankizumab, secukinumab, ixekizumab, or tildrakizumab) due to self-reported preference. Five themes resulted from the analysis: patients receiving injectables more frequently discussed the positive impact of the medication on quality of life compared to patients on oral medication; fear of side effects, particularly fear of immunosuppression, is associated with injection medications; avoidance of needles drives patients away from injection medication and towards oral systemic medication; patients prioritize convenience when selecting systemic therapy, though the definition of convenience is subject to perception; and patients value the medication recommendation of the physician, regardless of the route of administration. Conclusion: Improving medication adherence and disease outcomes through individualized treatment plans, with an emphasis on patients' preferences using a shared decision-making approach, may be helpful.

Residual disease is the main, but not the only factor impacting satisfaction in psoriatic patients undergoing biological therapies.

BACKGROUND: Despite advancements in psoriasis treatment, a gap remains in aligning patient satisfaction with clinical outcomes. Our study aimed to evaluate which clinical and psychological factors may impact treatment satisfaction in psoriatic patients undergoing long-term biological therapies. METHODS: We performed an observational, cross-sectional, single-center study involving adult patients with moderate-to-severe psoriasis treated with biologics for at least 12 months. We collected sociodemographic characteristics and data on the course of the psoriasis. We also assessed the absolute (residual) Psoriasis Area and Severity Index (PASI), the site of the residual disease, and the severity of pruritus through the Visual Analogue Scale (VAS). Satisfaction was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQMv.II). The Type D Personality Scale (DS14 questionnaire and Patient Health Questionnaire-9 assessed the psychological profile. RESULTS: Overall, 146 patients were included, and 82.1% were globally satisfied (global satisfaction TSQM score >75). Linear regression analysis showed a negative correlation between global satisfaction scoring and residual PASI. The multivariable analysis found a higher VAS-pruritus score (OR = 1.20, 95% CI = 1.01-1.44; P = 0.043) and not reaching a residual PASI < 2 (OR = 0.30, 95% CI = 0.09-0.94, P = 0.039) as the strongest predictors of global unsatisfied patients (TSQM < 75%). Other factors unrelated to residual disease, such as gender, class of biologic agent, and type D personality, have also been found to impact patient satisfaction. CONCLUSIONS: Our study's findings underscore the complexity of patient satisfaction in psoriasis management and highlight the multifactorial nature of treatment success beyond traditional clinical measures.

Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

Efficacy and Safety of Mepolizumab in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Single-Center Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic vasculitis characterized by eosinophil-rich, necrotizing granulomatous inflammation primarily affecting the respiratory tract with necrotizing vasculitis of small- to medium-sized arteries. In this case series, we retrospectively evaluated the efficacy and safety of mepolizumab in seven patients diagnosed with EGPA who presented to the Department of Allergy and Clinical Immunology at Cleveland Clinic Abu Dhabi. The variables assessed before and after mepolizumab treatment included Birmingham Vasculitis Activity Score (BVAS), prednisolone dose, Asthma Control Test (ACT) score, and blood eosinophil count (BEC). We found a significant reduction in BVAS and prednisolone dosage with clinical improvements in asthma symptoms after treatment with mepolizumab. Our case series, the first from the Middle East on the use of mepolizumab in EGPA, demonstrates that mepolizumab is a safe and effective treatment for patients with EGPA.

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement: Results of a retrospective cohort study.

BACKGROUND: Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis (JIA) with progressive disease course, polyarticular involvement and failure of methotrexate treatment. AIM: To describe features of JIA, associated with wrist arthritis. METHODS: Data from about 753 JIA patients were included in this retrospective cohort study. The clinical and laboratory features of patients with and without wrist involvement were analyzed. RESULTS: Wrist involvement was found in oligoarthritis (5.8%), RF(-)/RF(+) polyarthritis (44.9%/15.0%), enthesitis-related arthritis (17.7%), and systemic (58.6%) JIA categories. Unilateral wrist involvement was typical for oligoarthritis patients, bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories. Wrist arthritis was found to be associated with female sex, a low incidence of uveitis, and more indications of systemic inflammation, including elevated levels of C-reactive protein, erythrocyte sedimentation rate, and platelets, as well as involvement of the cervical spine, temporomandibular, shoulder, elbow, metacarpophalangeal, proximal interphalangeal, distal interphalangeal, hip, ankle, and tarsus arthritis. The number of patients with hip osteoarthritis and hip replacement was also higher. Wrist arthritis was associated with a lower probability of achieving remission [hazard ratio (HR) = 1.3 (95%CI: 1.0-1.7), P = 0.055], and a higher probability of being treated with biologics [HR = 1.7 (95%CI: 1.3-2.10, P = 0.00009)]. CONCLUSION: Wrist arthritis in JIA patients is a marker of a severe disease course, characterized by more intensive inflammation, unfavorable outcomes, and. requiring more intensive treatment with early administration of biologics. Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.