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Recent years have witnessed major advances and an ever-growing list of healthcare applications for microbiome-based therapeutics. However, these advances have disproportionately targeted diseases common in high-income countries (HICs). Within low- to middle-income countries (LMIC), opportunities for microbiome-based therapeutics include sexual health epidemics, maternal health, early life mortality, malnutrition, vaccine response and infectious diseases. In this review we detail the advances that have been achieved in microbiome-based therapeutics for these areas of healthcare and identify where further work is required. Current efforts to characterise microbiomes from LMICs will aid in targeting and optimisation of therapeutics and preventative strategies specifically suited to the unmet needs within these populations. Once achieved, opportunities from disease treatment and improved treatment efficacy through to disease prevention and vector control can be effectively addressed using probiotics and live biotherapeutics. Together these strategies have the potential to increase individual health, overcome logistical challenges and reduce overall medical, individual, societal and economic costs., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Eosinophilic gastrointestinal diseases (EGIDs) encompass a group of disorders characterized by an abnormal accumulation of eosinophils in various parts of the gastrointestinal tract. EGIDs present with a wide range of symptoms such as abdominal pain, vomiting, diarrhea, difficulty swallowing, and food impaction. Monoclonal antibodies, targeting inflammatory cytokines or eosinophils, are the next emerging therapy for EGIDs. The only Food and Drug Administration-approved monoclonal antibody is dupilumab, and it has been approved for the treatment of eosinophilic esophagitis (EoE). In this article, the authors will discuss biologics that have been used in the treatment of eosinophilic gastrointestinal diseases., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis., Methods: We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624)., Findings: Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I 2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I 2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I 2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I 2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I 2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I 2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I 2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I 2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I 2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains., Interpretation: In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD., Funding: None., Competing Interests: Declaration of interests SD declares grants from The Helmsley Charitable Trust, Edinburgh, Lothians Health Foundation, Pathological Society of Great Britain and Northern Ireland, and Lord Leonard and Lady Estelle Wolfson Foundation; consulting fees from AbbVie; personal speaker fees from Janssen, Ferring, and Takeda; and meeting and travel grants from Janssen, Takeda, Lilly, and Dr Falk. JB received a grant from Crohn's and Colitis UK and speaker fees from Thermo Fisher Scientific and Takeda. JS has received speaker fees for Takeda, Sandoz, Pfizer, and Bristol Myers Squibb; conference sponsorship from Takeda, Pfizer, Bristol Myers Squibb, and Jassen; and an unrestricted research grant from Tillots. BG has served as consultant to Galapagos, Pfizer, and AbbVie and as speaker for AbbVie, Janssen, Takeda, Pfizer, and Galapagos, and has received support for attending meetings by Dr Falk, Galapagos, Takeda, and Janssen. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license.)

Background: Randomised placebo-controlled trials are the gold standard to assess novel drugs in ulcerative colitis and Crohn's disease. However, there might be risks associated with receiving placebo. We aimed to examine the harms associated with receiving placebo in trials of licensed biologics and small molecules for the induction of remission in ulcerative colitis and luminal Crohn's disease in a meta-analysis., Methods: We performed a systematic review and meta-analysis. We searched MEDLINE, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials from database inception to May 30, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for induction of remission in adults (≥18 years) with moderately to severely active ulcerative colitis or luminal Crohn's disease reporting data on adverse events over a minimum treatment period of 4 weeks. There were no prespecified study exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, any drug-related adverse event, infection, worsening of inflammatory bowel disease (IBD) activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events (VTEs), reporting relative risks (RRs) with 95% CIs. The protocol for this meta-analysis was registered with PROSPERO (CRD42024527341)., Findings: The search identified 10 826 citations, of which 47 trials including 20 987 patients (14 267 [68·0%] receiving active drug and 6720 [32·0%] receiving placebo) were eligible. The risk of any treatment-emergent adverse event was no different with active drug than with placebo (7660/14 267 [53·7%] patients on active drug vs 3758/6720 [55·9%] on placebo; RR 0·97, 95% CI 0·94-1·00; I 2 =36%). However, the risks of worsening of IBD activity (563/13 473 [4·2%] vs 530/6252 [8·5%]; 0·48, 0·40-0·59; I 2 =54%), withdrawal due to adverse event (401/13 363 [3·0%] vs 299/6267 [4·8%]; 0·62, 0·48-0·79; I 2 =46%), serious adverse event (682/14 267 [4·8%] vs 483/6720 [7·2%]; 0·69, 0·59-0·80; I 2 =30%), serious infection (140/14 194 [1·0%] vs 91/6647 [1·4%]; 0·67, 0·50-0·89; I 2 =0%), serious worsening of IBD activity (187/11 271 [1·7%] vs 189/5056 [3·7%]; 0·45, 0·34-0·60; I 2 =27%), or VTEs (13/7542 [0·2%] vs 12/2981 [0·4%]; 0·45, 0·21-0·94; I 2 =0%) were all significantly lower with active drug than placebo. Numbers needed to treat with active drug to avoid these potentially serious adverse events ranged from 23 for worsening of IBD activity to 452 for VTEs. 27 randomised controlled trials were judged as low risk of bias across all domains., Interpretation: Patients with moderately to severely active IBD receiving placebo are more likely to experience significant worsening of IBD activity and some serious adverse events, which might relate to a reduction in risk of these events with active drug. Patients should be counselled about these potential harms, and alternative trial designs to mitigate these harms should be considered., Funding: None., Competing Interests: Declaration of interests SD declares grants from The Helmsley Charitable Trust, Edinburgh, Lothians Health Foundation, Pathological Society of Great Britain and Northern Ireland, and Lord Leonard and Lady Estelle Wolfson Foundation; is a consultant to AbbVie; speaker fees from Janssen, Takeda, and Ferring; and meeting and travel grants from Janssen, Takeda, Lilly, and Dr Falk. JB has received a grant from Crohn's and Colitis UK, speaker fees from Thermo Fisher Scientific and Takeda, and support for attending meetings from Janssen. JS has received speaker fees for Takeda, Sandoz, Pfizer, and Bristol Myers Squibb; support for attending meetings from Takeda, Pfizer, Janssen, and Bristol Myers Squibb; and an unrestricted research grant from Tillotts. BG is a consultant to Galapagos, Pfizer, and AbbVie, speaker for AbbVie, Jansen, Takeda, Pfizer, and Galapagos, and has received support for attending meetings from Dr Falk, Galapagos, Takeda, and Janssen. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The human microbiome, consisting of microorganisms that coexist symbiotically with the body, impacts health from birth. Alterations in gut microbiota driven by factors such as diet and medication can contribute to diseases beyond the gut. Synthetic biology has paved the way for engineered microbial therapeutics, presenting promising treatments for a variety of conditions. Using genetically encoded biosensors and dynamic regulatory tools, engineered microbes can produce and deliver therapeutic agents, detect biomarkers, and manage diseases. This review organizes engineered microbial therapeutics by disease type, emphasizing innovative strategies and recent advancements. The scope of diseases includes gastrointestinal disorders, cancers, metabolic diseases, infections, and other ailments. Synthetic biology facilitates precise targeting and regulation, improving the efficacy and safety of these therapies. With promising results in animal models, engineered microbial therapeutics provide a novel alternative to traditional treatments, heralding a transformative era in diagnostics and treatment for numerous diseases.

Objective: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme, that has been implicated as a biomarker of cardiovascular risk in patients with rheumatoid arthritis (RA). We aimed to investigate how different biologic therapies affect levels of PON1 and oxylipins., Methods: 1213 adult patients with RA in the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions cohort study with moderate-to-high disease activity (Clinical Disease Activity Index (CDAI) >10) who initiated a new biologic (tocilizumab (TCZ), n=296; abatacept, n=374; tumour necrosis factor inhibitors, n=427; rituximab, n=116) were followed prospectively with serum specimens analysed for PON1 activity by arylesterase (ARYL), lactonase (LAC) and PON assays at baseline and after 6 months of biologic therapy. A targeted panel of oxylipins was evaluated by liquid chromatography-mass spectrometry/mass spectrometry in a subset of patients with the lowest and highest 6-month Disease Activity Score 28 (DAS28)-C reactive protein (CRP) responses in each treatment group., Results: PON1 activity generally increased in the entire cohort after 6 months of new biologic therapy, showing the greatest, most consistent increases in the TCZ group. Increases in all three PON1 domains associated with significant decreases in disease activity in DAS28-CRP/CDAI (p<0.05), and increases in LAC/ARYL were significantly associated with the American College of Rheumatology 20/50/70 responses (OR (95% CI) of 1.12 (1.04, 1.22) and 1.13 (1.04, 1.23), p<0.01, respectively), after controlling for other RA disease characteristics. Some oxylipins, including 12-hydroxyeicosatetraenoic acid correlated with RA disease activity measures., Conclusion: Improvement in disease activity across four classes of biologics is associated with enhanced PON1 activity, which has significant implications for cardiovascular safety., Competing Interests: Competing interests: There are no competing interests to disclose for AAR, JMW, AS, DAE, RG, DM, DS, EO'C or STR. JMK is a consultant for EL. DAP is an employee with equity interests and scientific director at CorEvitas (part of Thermo Fisher, formerly known as Corrona), is a board member of Corrona Research Foundation (CRF) and a consultant with Novartis, Sanofi, Genentech, Roche and AbbVie. JRC has received grant support from and is a consultant for AbbVie, Amgen, Jannsen BMS, Genentech, Myriad, Pfizer, Lilly and Sanofi. CC-S has received grant support from Alexion, Priovant, CSL Behring, Janssen, Octapharma, Pfizer, AbbVie and Bristol-Myers Squibb, and is a consultant for Octapharma, Pfizer, AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Recludix and Galapagos., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess whether patient reported outcome measures (PROMs) improve after autologous conditioned serum (ACS) administration in patients with osteoarthritis., Methods: Databases and clinical trial registers were searched to March 2024 for randomised controlled trial (RCTs) comparing ACS vs comparators/controls. Primary outcomes were pain, function and stiffness measured with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS). Secondary outcome was complications. Risk of bias (RoB) and certainty of evidence were assessed using RoB 2 and the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) respectively. Meta-analysis was undertaken using RevMan v5.4. Results are presented as standardised mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI). Sensitivity analysis compared all comparators and saline control., Results: Five RCTs were identified (n = 741 participants); two (n = 529 participants) compared ACS against saline (placebo). Three studies were "some concern" and two studies "high risk" for bias. Analysis comparing ACS with all comparators significantly favoured ACS at 6 months for WOMAC: SMD -0.61 (95% CI -1.01 to -0.21; p = 0.003); and VAS: SMD -1.24 (95% CI -2.11 to -0.38; p = 0.005); with high heterogeneity. Comparing ACS with saline, there was no significant difference in WOMAC or VAS at 6 months: SMD -0.40 (95% CI -0.93 to 0.12; p = 0.13) and MD -9.87 (95% CI -27.73 to 7.98, p = 0.28). Complications were similar: ACS (24.8%) vs saline (24.4%), with serious complications rare., Conclusion: There is currently insufficient data to support the use of ACS in osteoarthritis with conflicting results when compared to alternative therapies and saline control, with high heterogeneity. Before consideration as a potential treatment, a high-quality multicentre RCT is required to assess the efficacy of ACS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: A novel immunomodulatory cytokine IL-41 is associated with the pathogenesis of Graves disease, Kawasaki disease, gout, psoriatic arthritis, and rheumatoid arthritis (RA). We aimed to evaluate serum IL-41 level as a biomarker of the RA and disease activity treatment efficacy and patient responses. We also wanted to determine eventual potential predictors of IL-41 concentrations. Methods and analysis: This observational clinical trial will enrol 189 patients rheumatology clinics of the Clinical Center Kragujevac, Serbia. Participants will be divided into three groups: patients on methotrexate monotherapy (MTX), (n=31), those treated with combined therapy of MTX plus TNF inhibitors (TNFi) (n=70), and patients treated with monotherapy with IL-6 inhibitor tocilizumab (TCZ) (n=43). Newly diagnosed RA or patients who for some reason were excluded from the DMARDs for a minimum of 3 months were considered as the control group (n=45). Results: TCZ reduced the IL-41 level the most. All treatment options significantly reduced clinical signs, symptoms and the scores of disease activity composite indices, TCZ the most. The only statistically significant predictor of higher IL-41 values was smoking. Conclusion: IL-41 may be a new potential biomarker that can help physicians evaluate treatment efficacy and predict patient responses. Smoking status is associated with the higher concentration of IL- 41 and clinical presentation of patients with RA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants., Methods: We identified PIBD patients receiving infliximab, adalimumab, vedolizumab, or ustekinumab at the Children's Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses., Results: Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22)., Conclusions: Benign ALT elevation is common within 3 months after starting BT (especially infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Biological medications have significantly improved the prognosis of psoriasis patients. All biological drugs (except infliximab) for psoriasis require subcutaneous (SC) administration. Adverse events of biologic drug treatment include injection site reactions. ISRs are a local phenomenon characterized by swelling, erythema, pruritus, and pain around the injection site., Areas Covered: We conducted a review to analyze the differences between the ISRs of various biologics approved for psoriasis. Specifically, the review focused on anti-TNF-α, anti-IL12/23, anti-IL-17, and anti-IL-23 drugs., Expert Opinion: Etanercept and adalimumab have reported ISR rates of 37% and 20%, respectively, with erythema, pruritus, pain, and irritation being the most common. Citrate free (CF) solution and thinner needles have reduced ISR associated with adalimumab. Ustekinumab showed a low risk of ISR. Regarding secukinumab and ixekizumab, pain was found to be the most common ISR. The introduction of CF ixekizumab formulation has shown promise in reducing ISRs associated with ixekizumab. The risk of ISR appears insignificant with bimekizumab, brodalumab, and anti-IL23 drugs, with ISR rates ranging from less than 1% to 7.1%. The choice of biologic agent should consider ISR risk. Education on injection techniques and the use of single-dose autoinjectors/pens can mitigate ISR risk.

Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into NAD + within the body after ingestion. NMN plays a pivotal role in several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. NMN has emerged as a key focus of research in the fields of biomedicine, health care, and food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights into the pathogenesis of age- and aging-related diseases. Given the sustained global research interest in NMN and the substantial market expectations for the future, here, we comprehensively review the milestones in research on NMN biotherapy over the past 10 years. Additionally, we highlight the current research on NMN in the field of digestive system diseases, identifying existing problems and challenges in the field of NMN research. The overarching aim of this review is to provide references and insights for the further exploration of NMN within the spectrum of digestive system diseases., (© 2024. The Author(s).)

Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.

Treatment of pyoderma gangrenosum (PG) is challenging due to the absence of standardized guidelines and the lack of evidence-based, effective treatment options. Here, we performed a systematic review to summarize the use of biologics and their efficacy in the treatment of PG. We searched PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to September 22nd, 2022, and included 82 peer-reviewed studies with a total of 108 patients. Infliximab, adalimumab, and etanercept were the most utilized biologic therapies in the treatment of PG in 64.8% (70/108), 16.7% (18/108), and 11.1% (12/108) of the cases, respectively. With respect to treatment response, 88.9% (96/108) of the patients achieved complete resolution of PG with biologic therapies. The average number of days to improvement and resolution of PG treated after starting biologic therapies was 30 and 161, respectively. PG recurred in 15.5% (11/71) of those reported the outcome. Our study suggests that biologic therapies may be an attractive therapeutic option for PG with an excellent efficacy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nowadays, biological therapies are booming and more of these formulations are coming to the market. Platelet-rich plasma, or PRP, is one of the most widely used biological therapies due to its ease of obtention and autologous character. Most of the techniques to obtain PRP are focusing on new processes and methods of optimization. However, not enough consideration is being given to modify the molecular components of PRP to generate more effective formulations with the aim of improving PRP treatments. Therefore, this review covers different novel PRP-obtaining methods that attempt to modify the molecular composition of the plasma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Jon Mercader-Ruiz et al.)

Background and Aims: STRIDE-II recommends early biomarker targets for treatment optimization to achieve treat-to-target [T2T] endoscopic remission [ER] in Crohn's disease [CD]. The predictive capabilities of intestinal ultrasound [IUS] for T2T ER remain unknown. We aimed to evaluate IUS response to predict ER in children with CD., Methods: This was a prospective longitudinal cohort study of children with ileal [TI] CD initiating biologic therapy undergoing IUS, clinical disease activity, and C-reactive protein [CRP] assessments at baseline, week 8, 6 months, and T2T within 1 year. The primary outcome was the accuracy of optimal cut-points to predict TI ER [SES-CD ≤ 2] for change in bowel wall thickness [BWT] on IUS from baseline to week 8, and BWT at week 8. Area under the receiver operating curve [AUROC] analysis was performed and univariate analysis tested associations., Results: In total, 44 children (median age 13 [IQR 12-17] years, 29 [66%] biologic naïve) were included, and 29 [66%] achieved ER. A ≥18% decrease in TI BWT at week 8 predicted ER with an AUROC of 0.99 [95% CI 0.98-1.00], 100% sensitivity, 93% specificity, 97% positive predictive value, and 100% negative predictive value, superior to a ≥46% decrease in PCDAI (AUROC 0.67 [95% CI 0.49-0.84]) and ≥84% decrease in CRP (AUROC 0.49 [95% CI 0.31-0.67]) at week 8., Conclusions: Early change in TI BWT on IUS is highly predictive of ER in children with CD and superior to symptoms and CRP. Our findings suggest that IUS could be used for treatment optimization and tight control to guide T2T strategies., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: Micronutrient deficiencies are common in patients with inflammatory bowel disease (IBD), but whether they relate to disease outcomes remains unknown. This study assessed the micronutrient status of adults with IBD on treatment with biologic therapies and explored predictive relationships with disease outcomes., Methods: Seventeen micronutrients were measured in the blood of 216 adults with IBD on biologic therapy. Of these, 127 patients (58%) had Crohn's disease (CD), and the majority (70%) received treatment with infliximab. Patients were followed for 12 months and onset of adverse clinical outcomes (eg, requirement for treatment with corticosteroids, hospitalization, or surgical intervention) was recorded, and related to micronutrient status., Results: Among all patients, the most common deficiencies were for vitamin C (n = 35 of 212 [16.5%]), ferritin (n = 27 of 189 [14.3%]), folate (n = 24 of 171 [14.0%]), and zinc (n = 27 of 210 [12.9%]). During follow-up, 22 (10%) of the 216 patients developed 1 or more adverse clinical outcomes. Patients with CD and zinc deficiency were significantly more likely to require surgery (P = .002) or treatment with corticosteroids (P < .001). In contrast, patients with ulcerative colitis and selenium deficiency were significantly more likely to have a clinical flare of disease (P = .001), whereas those with CD were not. This relationship with selenium remained significant after adjustment for confounders., Conclusions: A substantial proportion of adults with IBD present deficiencies for certain micronutrients, with selenium and zinc deficiency predicting adverse disease outcomes. For other micronutrients, deficiencies were less common and should not warrant routine screening. Intervention studies should explore the effect of micronutrient supplementation in modifying disease outcomes in IBD., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Introduction: The advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In systemic lupus erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs., Areas Covered: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis., Expert Opinion: An unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

Introduction: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables., Aim: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay., Methods: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication., Results: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval., Conclusion: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of the sinonasal cavities classified into two major phenotypes: CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The diagnosis of CRS is based on clinical symptoms associated with imaging and/or nasal endoscopy findings of mucosal inflammation., Recent Findings: Recently, novel biological therapies have emerged as therapeutic options for CRSwNP. Imaging is helpful in deciding whether surgery is likely to be beneficial and in guiding surgery. It can also help demonstrate a clinical response to medical therapy. However, specific guidelines concerning the role of imaging in CRwNP are lacking., Summary: This article provides a comprehensive and critical multidisciplinary review of the role of conventional radiology, computed tomography (CT), and magnetic resonance imaging (MRI) in the diagnosis and characterization of CRSwNP. Since the complete characterization of nasal polyps on CT or MR images is very challenging, we provide a critical review of the best imaging methods and essential reporting elements used to assess nasal polyps., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Eosinophilic otitis media, first reported in Japan, is a viscous, intractable otitis media often linked to bronchial asthma and chronic rhinosinusitis, characterized by highly viscous middle ear effusion. Its pathological mechanism remains unclear and the condition occasionally does not respond to steroids. It is now recognized as a rare type 2 inflammatory disease and should be treated specifically to enhance quality of life. This systematic review and meta-analysis evaluated the efficacies of biologic treatments. We searched PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to September 2023. We retrieved ear examination findings, otitis media-related and symptom scores, air-bone gaps and hearing thresholds, serum eosinophil, and immunoglobulin E (IgE) levels before and after biologic treatments. Biologics treatment significantly improved subjective otitis media-related scores, compared with control group (standard mean difference (SMD) -1.62; 95% confidence interval (CI) [-2.24; -1.01], I2=54%). Additionally, the serum eosinophil counts and IgE levels significantly decreased (SMD -1.40; 95% CI [-1.99; -0.81], I 2=0%) after 6-12 months of biologic treatments, but the hearing thresholds did not significantly change. There were no significant differences between groups treated with dupilumab and groups treated with other biologics. Biologics treatment for eosinophilic otitis media significantly improved subjective otitis media-related scores and decreased serum eosinophil and IgE levels, but no significant changes in hearing threshold. More randomized cohort studies are needed to confirm the efficacies of biologics in patients with refractory eosinophilic otitis media.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies., Competing Interests: Conflict of interest statement. F.R. receives consultancy and/or speaker fees from GlaxoSmithKline, AstraZeneca, Menarini, and Merck. F.L.K. receives research funding from AstraZeneca and speaker fees from both AstraZeneca and GlaxoSmithKline. S.J.A. is the Chief Scientific Officer and an Executive Board member of EnteroTrack, LLC; a co-inventor and holds patents on the Esophageal String Test; and a consultant for Areteia Pharmaceuticals. P.A. has received consulting fees and research support from AstraZeneca, GlaxoSmithKline, and Sanofi and research support from Regeneron. B.S.B. receives remuneration for serving on the scientific advisory board of Allakos, Inc.; owns stock in Allakos; currently serves as a consultant for Third Harmonic Bio and Sanofi/Regeneron; receives publication-related royalty payments from Elsevier and UpToDate; is a co-inventor on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products; and is a co-founder of Allakos, which makes him subject to certain restrictions under university policy (the terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict-of-interest policies). M.W.J. has received research funding from F. Hoffmann-La Roche. S.K.M. has received consulting, advisory, or speaking honoraria from AstraZeneca, Amgen, GlaxoSmithKline, Novartis, and Sanofi/Regeneron. P.O.B. receives research funding from GlaxoSmithKline, AstraZeneca, Blueprint, and DBV Technologies; and serves on advisory boards for AstraZeneca, Sanofi, Genentech, and Kalvista. M.E.W. has received consulting, advisory, or speaking honoraria from Amgen, Areteia Therapeutics, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim, Celldex, Cellergy Pharma, Cerecor, Cytoreason, Eli Lilly, Equillium, Glaxosmithkline, Incyte, Kinaset, Merck, Novartis, Om Pharma, Overtone Therapeutics/Foresite Labs, Phylaxis, Pulmatrix, Rapt Therapeutics, Regeneron, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Tetherex Pharmaceuticals, Teva, Upstream Bio, and Verona Pharma. The other authors have no conflicts of interest to disclose., (Published by Oxford University Press on behalf of Society for Leukocyte Biology 2024.)

Background: Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited., Objectives: The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an 'as needed' approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care., Methods: We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on 'as needed' biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis., Results: Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of 'as needed' biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of 'as needed' drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9-64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8-33)]. Both patients and clinicians felt that an 'as needed' treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an 'as needed' approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence., Conclusions: These data indicate that 'as needed' biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized., Competing Interests: Conflicts of interest D.G. has received educational support from Lilly. L.M. has attended conferences, spoken at meetings and attended advisory boards for the following companies: AbbVie, Almirall, BMS, Janssen-Cilag, LEO, Lilly, Novartis, ONO Pharma, Pfizer and UCB. H.M. and G.S. are employed by the Psoriasis Association, which has received unrestricted educational grants over the past two years from Almirall, AbbVie, Janssen, Amgen, Eli Lilly, Dermal, UCB, LEO Pharma, Bristol Myers Squibb and Novartis. J.N.W.N.B. has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sienna, Sun Pharma and UCB. C.H.S. reports grants from a Medical Research Council-funded stratified medicine consortium with multiple industry partners (PSORT.org), grants from an IMI (Horizon 2020)-funded European consortium with multiple industry partners (BIOMAP-IMI.eu, HIPPOCRATES-IMI.eu, and others) and grants from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and Swedish Orphan Biovitrum, outside the submitted work; and is Chair of UK guidelines on biologic therapy in psoriasis. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Sanofi and UCB, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: This study's purposes were to evaluate the impact of biological therapies on outcomes in patients with severe asthma (SA) and chronic rhinosinusitis (CRS) and to compare these effects among those with NP (CRSwNP) versus those without NP (CRSsNP) in the "real-world" setting in Saudi Arabian patients., Methods: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of dupilumab therapy. Outcomes were assessed, including clinical outcomes, FEV1, and laboratory findings before and one year after dupilumab. Post-therapy effects were compared between CRSwNP and CRSsNP., Results: Fifty subjects were enrolled, with a mean age of 46.56. There were 27 (54%) females and 23(46%) males. Significant improvements in clinical parameters (frequency of asthma exacerbations and hospitalizations, the use of OCs, anosmia, SNOTT-22, and the ACT), FEV1, and laboratory ones (serum IgE and eosinophilic count) were observed 6 and 12 months after using dupilumab (p < 0.001), respectively. However, after 12 months of dupilumab therapy, there were no significant differences between those with and without NP with regards to clinical (anosmia, ACT, and OCs use), laboratory (eosinophilic count, serum IgE level) parameters, and FEV1%., Conclusions: Patients with CRS experienced significant improvements in clinical, FEV1, and laboratory outcomes after dupilumab therapy. However, these improvements were not maintained when comparing CRSwNP with CRSsNP. There were no significant differences between those with and without NP regarding ACT and OCs use or laboratory (eosinophilic count, serum IgE level) parameters. Further prospective multicenter studies are warranted., (© 2024. The Author(s).)

Background and Aims: Inflammatory bowel disease (IBD) can lead to long-term complications that significantly impact patients' quality of life and healthcare resource utilization. Prior studies have demonstrated improved short-term outcomes to early exposure of biologics in patients with Crohn's disease (CD) but not in patients with ulcerative colitis (UC). However, there are conflicting data on impact of early intervention on longer-term adverse events. Therefore, we conducted a systematic review and meta-analysis assessing the impact of early biologic treatment on rates of IBD-related surgery., Methods: A systematic search was conducted in April 2022. Studies were included if biologic initiation was compared between patients starting early (<3 years of diagnosis or top-down treatment) vs later (>3 years of diagnosis or step-up treatment). Studies with <1 year of follow-up were excluded. The outcomes were colectomy and CD-related surgery for patients with UC and CD, respectively. Random-effects analyses were conducted to compare rates of IBD surgery between early and late biologic treatment., Results: Eighteen studies were included in the meta-analysis. Three studies included patients with UC and 15 studies included patients with CD. In patients with CD, early biologic therapy was associated with lower odds of surgery (odds ratio, 0.63; 95% confidence interval, 0.48-0.84) compared with late treatment. Conversely, in patients with UC, the odds of colectomy were increased (odds ratio, 2.86; 95% confidence interval, 1.30-6.30)., Conclusions: Early biologic treatment is associated with lower rates of surgery in patients with CD. In contrast, early biologic therapy appears to be associated with higher rates of colectomy in patients with UC, which may be confounded by disease severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD., Methods: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ)., Results: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission., Conclusions: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP)., Data Sources: PubMed, MEDLINE, Cochrane, and clinical trial registries., Review Methods: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases., Conclusions: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease., Implications for Practice: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

N-glycosylation of the Fc part is a (critical) quality attribute of therapeutic antibodies and Fc-containing biotherapeutics, that impacts their stability, immunogenicity, pharmacokinetics, and effector functions. Current glycosylation analysis methods focus on the absolute amounts of glycans, neglecting the apparent glycan distribution over the entirety of proteins. The combination of the two Fc N-glycans, herein referred to as glyco-pair, therefore remains unknown, which is a major drawback for N-glycan impact assessment. This study presents a comprehensive workflow for the analysis and characterization of Fc N-glycan pairing in biotherapeutics, addressing the limitations of current glycosylation analysis methods. The applicability of the method across various biotherapeutic proteins including antibodies, bispecific antibody formats, and a Fc-Fusion protein is demonstrated, and the impact of method conditions on glycan pairing analysis is highlighted. Moreover, the influence of the molecular format, Fc backbone, production process, and cell line on glycan pairing pattern was investigated. The results underscore the significance of comprehensive glycan pairing analysis to accurately assess the impact of N-glycans on important product quality attributes of therapeutic antibodies and Fc-containing biotherapeutics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maximilian Meudt, Julia Baumeister, Michaela Blech and Fabian Higel are employees of Boehringer Ingelheim GmbH & Co. KG, which is developing, manufacturing, and marketing biopharmaceutical products., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type‑2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD., Methods: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics., Results: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B‑SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control., Conclusion: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy., (© 2024. The Author(s).)

Severe asthma is a complex and heterogeneous chronic airway inflammatory disease. Current treatment strategies are increasingly focused on disease classification, facilitating the transition towards personalized medicine by integrating biomarkers and monoclonal antibodies for tailored therapeutic approaches. Several approved biological agents, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-4, anti-IL-5, and anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, have demonstrated significant efficacy in reducing asthma exacerbations, eosinophil counts, improving lung function, minimizing oral corticosteroid usage, and enhancing patients' quality of life. The utilization of these biological agents has brought about profound transformations in the management of severe asthma. This article provides a comprehensive review on biomarkers and biological agents for severe asthma while emphasizing the increasing importance of further research into its pathogenesis and novel treatment modalities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure., Methods: Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups., Results: In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p < 0.001 and p < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [p = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [p = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF., Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Introduction: Advanced hepatocellular carcinoma (HCC) represents a significant global health burden, whose treatment has been recently revolutionized by the advent of biologic treatments. Despite that, innovative therapeutic regimens and approaches, especially immune-based, remain to be explored aiming at extending the therapeutic benefits to a wider population of patients., Areas Covered: This review comprehensively discusses the evolving landscape of biological treatment modalities for advanced HCC, including immune checkpoint inhibitors, antiangiogenic monoclonal antibodies, tumor-targeting monoclonal antibodies either naked or drug-conjugated, therapeutic vaccines, oncolytic viruses, adoptive cell therapies, and cytokine-based therapies. Key clinical trials and preclinical studies are examined, highlighting the actual or potential impact of these interventions in reshaping treatment paradigms for HCC., Expert Opinion: Tailored and rational combination strategies, leveraging the synergistic effects of different modalities, represent a promising approach to maximize treatment efficacy in advanced HCC, which should aim at conversion endpoints to increase the fraction of patients eligible for curative approaches. The identification of predictive biomarkers holds the key to optimizing patient selection and improving therapeutic outcomes.

Many diseases originate from either the absence or defective expression of a given protein. For some of them, the lacking protein is secreted or can be taken up by cells when delivered exogenously. In such cases, therapies initially involved administering the physiological protein extracted from human tissues. Subsequently, genetic engineering enabled the production of proteins through cell fermentation after introducing the corresponding gene. For many other pathologies, the deficient protein cannot be delivered exogenously. Thus, an endogenous production of the therapeutic protein by the cells themselves is necessary. Messenger RNA (mRNA) technology, like its predecessor DNA, aims to supplement the genetic information needed to produce the therapeutic protein within the cells. However, unlike DNA-based therapies, mRNA transfer allows for transient expression of the protein of interest, which offers an advantage in numerous pathologies. Nonetheless, mastering the quantity, quality, and spatio-temporal regulation of protein production encoded by therapeutic mRNA remains a significant challenge for the development of this approach., (© 2024 médecine/sciences – Inserm.)

Introduction: Biological therapies have become the standard treatment for ulcerative colitis (UC). However, clinical remission rates post-induction therapy remain modest at 40-50%, with many initial responders losing response over time. Current treatment strategies frequently rely on a 'trial and error' approach, leading to prolonged periods of ineffective and costly therapies for patients, accompanied by associated treatment complications., Area Covered: This review discusses current evidence on risk stratification tools for predicting therapeutic efficacy and minimizing adverse events in UC management. Recent studies have identified predictive factors for biologic therapy response. In the context of personalized medicine, the goal is to identify patients at high risk of progression and complications, as well as those likely to respond to specific therapies. Essential risk stratification tools include clinical decision-making aids, biomarkers, genomics, multi-omics factors, endoscopic, imaging, and histological assessments., Expert Opinion: Employing risk stratification tools to predict therapeutic response and prevent treatment-related complications is essential for precision medicine in the biological management of UC. These tools are necessary to select the most suitable treatment for each individual patient, thereby enhancing efficacy and safety.

Introduction: Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology population has not previously been well documented and a retrospective review was undertaken to quantify the potential cost benefits., Methods: A retrospective chart review of patients with an oncologic diagnosis was performed for cytotoxic agents, asparaginase products, and biotherapy administered between January 1, 2014, and December 31, 2017. In the analysis, orders that could be rounded down to the nearest vial size by 5 or 10% were included. Medication pricing information was based on wholesale acquisition cost (WAC) and was provided by the Department of Pharmacy. Cost savings per medication were determined by multiplying the WAC of the medication by the number of vials saved., Results: Over a 4-year span, 347 patients were evaluated and 552 out of a possible 3110 orders (17.7%) met criteria for a theoretical cost savings of approximately $1,126,000 (∼$3200 per patient). Rounding down doses by up to 5% resulted in a potential savings of about $529,000. When rounding was extended to 5-10% of the originally ordered dose, an additional $597,000 of approximate cost savings could have been realized. The medications with the largest impact on cost savings were rituximab, pegaspargase, and erwinia asparaginase., Conclusions: For pediatric oncology patients, there exists a unique potential cost savings opportunity if doses are rounded down within 5 or 10% of the originally ordered weight-based or body surface area-calculated dose., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Approximately 20-30% of the patients with ulcerative colitis (UC) may present with isolated proctitis. Ulcerative proctitis (UP) is a challenging condition to manage due to its significant burden in terms of disabling symptoms., Areas Covered: PubMed was searched up to March 2024 to identify relevant studies on UP. A comprehensive summary and critical appraisal of the available data on UP are provided, highlighting emerging treatments and areas for future research., Expert Opinion: Patients with UP are often undertreated, and the disease burden is often underestimated in clinical practice. Treat-to-target management algorithms can be applied to UP, aiming for clinical remission in the short term, and endoscopic remission and maintenance of remission in the long term. During their disease, approximately one-third of UP patients require advanced therapies. Escalation to biologic therapy is required for refractory or steroid dependent UP. For optimal patient care and management of UP, it is necessary to include these patients in future randomized clinical trials.

Background and Aims: Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes., Methods: Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years. A logistic regression analysis was performed to assess the prognostic value of different radiologic findings for various predefined adverse outcomes., Results: Of the 89 patients included, 46 (51.7%) had ≥1 adverse outcome during follow-up: 40 (44.9%) had clinical recurrence; 18 (20.2%) required surgery, 8 (9%) endoscopic balloon dilation, 12 (13.5%) hospitalization and 7 (7.8%) required corticosteroids. In the multivariate analysis, persistence of severe lesions (MaRIA ≥11) in any intestinal segment was associated with an increased risk of surgery [OR 11.6 (1.5-92.4)], of surgery and/or endoscopic balloon dilation [OR 6.3 (1.3-30.2)], and of clinical relapse [OR 4.6 (1.6-13.9)]. Penetrating lesions were associated with surgery [OR 3.4 (1.2-9.9)]. Creeping fat with hospitalization [OR 5.1 (1.1-25.0)] and corticosteroids requirement [OR 16.0 (1.2-210.0)]. The presence of complications (stricturing and/or penetrating lesions) was associated with having ≥1 adverse outcome [OR 3.35 (1.3-8.5)]., Conclusion: MRE findings at week-46 after initiating biological therapy can predict long-term adverse outcomes in CD. Therapeutic intervention may be required in patients with persistence of severe inflammatory lesions, CD-associated complications, or creeping fat., (© 2024 John Wiley & Sons Ltd.)

The prevalence of asthma among the elderly population has witnessed a notable rise, presenting unique challenges in diagnosis and management. Biologic therapies, such as omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, have demonstrated efficacy in targeting specific pathways associated with severe asthma in elderly individuals. However, a significant research gap exists in the application of these therapies in elderly asthma patients. Despite the considerable size of the elderly asthma population and the social and economic burden that this specific demographic imposes on society, the available body of research catering to this group is limited. Notably, no RCTs have been expressly designed for the elderly across all asthma biologic therapies. Moreover, most RCTs have set upper age cutoffs, commonly 75 years old, and exclusion criteria for common comorbidities in the elderly, thus marginalizing this group from pivotal research. This underscores the crucial need for intentional inclusion of elderly participants in separately designed clinical trials and more researches, aiming to augment the generalizability of findings and enhance therapeutic outcomes. Given the distinct physiological changes associated with aging, there may be a concern regarding the efficacy and safety of biologic therapies in the elderly compared to non-elderly adults, posing a barrier to their use in this population. However, observational studies have shown similar benefits of these therapies in elderly individuals as seen in non-elderly adults. Other anticipated challenges related to initiating biologic therapy in elderly people with asthma including dosing consideration and monitoring strategies, which are important areas of investigation for optimizing asthma management will be discussed in this review. In summary, this review navigates the current landscape of biologic therapies for elderly asthma, offering valuable insights for various stakeholders, including researchers, healthcare providers, and policymakers, to advance asthma care in this vulnerable population. We propose that future research should concentrate on tailored, evidence-based approaches to address the undertreatment of elderly asthma patients., Competing Interests: Declaration of competing interest All authors have no conflict of interest to report., (Copyright © 2024. Published by Elsevier Ltd.)

Malignant tumors pose a grave threat to the quality of human life. The prevalence of malignant tumors in China is steadily rising. Presently, clinical interventions encompass surgery, radiotherapy, and pharmaceutical therapy in isolation or combination. Nonetheless, these modalities fail to completely eradicate malignant tumor cells, frequently leading to metastasis and recurrence. Conversely, tumor biotherapy has emerged as an encouraging fourth approach in preventing and managing malignant tumors owing to its safety, efficacy, and minimal adverse effects. Currently, a range of tumor biotherapy techniques are employed, including gene therapy, tumor vaccines, monoclonal antibody therapy, cancer stem cell therapy, cytokine therapy, and adoptive cellular immunotherapy. This study aims to comprehensively review the latest developments in biological treatments for malignant tumors., (© 2024. The Author(s).)