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Background: Psoriasis is a chronic inflammatory skin disorder with significant impact on quality of life. The evolving landscape of treatment modalities includes traditional therapies and newer biologic agents. This study systematically reviews the efficacy and safety of various psoriasis treatments to guide clinical decision-making. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov, yielding 45 studies that met the inclusion criteria. These studies were categorized into four treatment groups: topical, phototherapy, systemic, and biologic therapies. Data on efficacy, measured by PASI score reduction, and safety were extracted and analyzed. Results: Biologic therapies targeting TNF-α, IL-12/23, and IL-17 demonstrated the highest efficacy with mean PASI reductions of 75%, 72%, and 78%, respectively. Systemic therapies such as methotrexate and cyclosporine showed mean PASI reductions of 65% and 70%. Topical treatments and phototherapy also proved effective but were less impactful compared to biologics. Safety profiles varied, with biologics associated with increased risk of infections and injection site reactions, while systemic therapies had notable risks of organ toxicity. Conclusion: Biologic therapies represent a significant advancement in psoriasis management, offering superior efficacy for moderate to severe cases. However, their high cost and potential side effects highlight the need for personalized treatment approaches. Traditional therapies remain valuable, particularly for milder forms or as adjunctive treatments. Future research should focus on long-term safety and efficacy, and strategies to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry. Methods The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories. Conclusion Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. Trial registration Clinicaltrials.gov, NCT01357668. [ABSTRACT FROM AUTHOR]

Objective To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA). Methods Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight–based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE. Results Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). Conclusion Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile. Clinical trial registration clinicaltrials.gov, NCT02165345 [ABSTRACT FROM AUTHOR]

Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD‐LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra‐cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long‐term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD‐LBP and summarizes effects of therapies aimed for CD‐LBP with special emphasis on chronic pain. Approaches based on blocking pro‐inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD‐LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in‐depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD‐LBP could help narrow the gap between the pre‐clinical bench and clinical bedside for novel CD‐LBP therapeutics and optimize pain treatment. [ABSTRACT FROM AUTHOR]

Prompt disease control of flares in patients with systemic lupus erythematosus (SLE) is a priority in treatment strategy planning. However, the long-term dosage-related collateral effects of glucocorticoids (GCs) have pushed researchers towards the identification and utilization of novel biological agents that could both induce and maintain low disease activity and remission, especially in the context of lupus nephritis (LN). This scoping review aims at assessing the current evidence of the potential steroid-sparing effect of biologic therapies by reviewing phase II and phase III randomized, placebo-controlled trials involving SLE/LN patients. A scoping review of the literature was carried out in accordance with PRISMA-ScR recommendations. Risk of bias was assessed through the utilization of the Cochrane Collaboration's tool for randomized controlled trials (RCTs). Eight RCTs met the inclusion criteria and were included in this analysis (treatment drug, 7 belimumab; 1 anifrolumab). Four studies showed a definite steroid-sparing effect (treatment drug, 3 belimumab; 1 anifrolumab), while in the remaining four RCTs, the steroid-sparing effect was not observed. When focusing on phase III trials, the overall quality of the studies resulted fair or good considering the risk of bias. However, a degree of heterogeneity of steroid regimen protocol (considering initial dosage, tapering and rescue treatment allowance) was observed. While a growing body of evidence is supporting the safety and efficacy of biological treatment in SLE, the evidence on their steroid-sparing effect remains scattered. Future research needs to pursue the identification of precise SLE clusters of patients who would benefit most from a specific treatment protocol with a definite steroid-sparing effect. [ABSTRACT FROM AUTHOR]

Abstract Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD‐LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra‐cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long‐term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD‐LBP and summarizes effects of therapies aimed for CD‐LBP with special emphasis on chronic pain. Approaches based on blocking pro‐inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD‐LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in‐depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD‐LBP could help narrow the gap between the pre‐clinical bench and clinical bedside for novel CD‐LBP therapeutics and optimize pain treatment.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissueengineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions. [ABSTRACT FROM AUTHOR]

The skin is the body's largest organ and creates the initial impression when interacting with others. Thus, dermatological conditions can have a profound impact on the quality of life, affecting both mental and physical well-being. The increasingly common use of new biological therapies in dermatology for conditions such as psoriasis, atopic dermatitis, and chronic urticaria represents hope for these patients, significantly improving their quality of life. Interleukin -17, -23, -4, -13 inhibitors (ixekizumab, guselkumab, tildrakizumab, secukinumab, dupilumab) target molecules involved in the onset of these diseases and manage to provide patients with sustained efficacy over time, with an optimal safety profile. Results have been quantified using scores such as PASI (Psoriasis Area and Severity Index), DLQI (Dermatology Life Quality Index), GAD-7 (Generalized Anxiety Disorder scale-7), analyzed by specialist physicians, revealing significant improvements following biological therapies. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Pouchitis is a common complication after restorative ileal pouch–anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic‐dependent or antibiotic‐refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15–20% of patients, is challenging to treat. The efficacy of second‐line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real‐world efficacy data from peer‐reviewed full‐text manuscripts, focusing on immunomodulator and biologic therapies in CP. Methods Embase and PubMed databases were searched for full‐text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti‐integrin, and interleukin‐12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed. Results Pooled analysis comprised 20 full‐text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35–59%) and clinical remission rate was 35% (95% CI: 21–52%). Overall endoscopic response and remission rates were 41% (95% CI: 18–68%) and 15% (95% CI: 5–39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable. Conclusion The real‐world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti‐TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real‐world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.

Sjögren disease (SjD) in children is a rare disease phenotype, categorized with onset before the age of 18. Due to differences in clinical presentation in children and young people compared with adults, the disease is under-recognised and under-diagnosed in younger patients. Consequently, no evidence-based treatment and management recommendations are available for children with SjD, despite efforts to develop paediatric expert-led consensus guidelines in recent years and incorporate management recommendations for children in adult guidelines. This article highlights the potential differences in assessment strategies for children and young people compared with adults due to differences in clinical manifestations and screening tests between SjD in children and adult-onset SjD. Furthermore, it summarises the evidence concerning the use and efficacy of various treatments in children with SjD. Higher-quality research is needed to evaluate the safety and efficacy of various off-label treatments used or recommended for use in child patients with SjD and investigate long-term disease outcomes. [ABSTRACT FROM AUTHOR]

Traditional treatment strategies for acute myeloid leukemia (AML) have primarily relied on standard chemotherapy regimens for four decades. Indeed, the landscape of AML therapy has evolved substantially in recent years, mainly due to the introduction of hypomethylating agents and small molecules. Bcl2 inhibitor venetoclax, Fms-like tyrosine kinase 3 (FLT3) inhibitors such as midostaurin and gilteritinib, and isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) inhibitors ivosidenib and enasidenib, as well as hedgehog (HH) pathway inhibitor glasdegib represented a significant step forward in AML therapeutic armamentarium. Smoothened (SMO) inhibitor in combination with low-dose cytarabine marks a recent milestone. Ivosidenib, the first-in-class, selective, allosteric IDH1R132 inhibitor, showed the capability to induce in vitro differentiation of primary mIDH1 AML blasts. Clinical data highlighted its exceptional safety profile, as a standalone therapy and in combination strategy. Additionally, comprehensive studies consistently demonstrated its effectiveness, both in monotherapy and in association with chemotherapy. The identified ivosidenib's strengths, including its remarkable safety record and ability to yield positive therapeutic outcomes, position it as an ideal partner for both classic chemotherapy and biological treatments, i.e. hypometilant agents and/or venetoclax. Further studies are warranted to explore strategies for overcoming the occurrence of ivosidenib resistance. [ABSTRACT FROM AUTHOR]

Background and Aim: Pouchitis is a common complication after restorative ileal pouch–anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic‐dependent or antibiotic‐refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15–20% of patients, is challenging to treat. The efficacy of second‐line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real‐world efficacy data from peer‐reviewed full‐text manuscripts, focusing on immunomodulator and biologic therapies in CP. Methods: Embase and PubMed databases were searched for full‐text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti‐integrin, and interleukin‐12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed. Results: Pooled analysis comprised 20 full‐text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35–59%) and clinical remission rate was 35% (95% CI: 21–52%). Overall endoscopic response and remission rates were 41% (95% CI: 18–68%) and 15% (95% CI: 5–39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable. Conclusion: The real‐world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti‐TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real‐world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP. [ABSTRACT FROM AUTHOR]

The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments. [ABSTRACT FROM AUTHOR]

Background: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. Objective: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. Methods: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. Results: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6–14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52–54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. Conclusion: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Background: Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both their clinical use and the development of novel regimens. However, the identification and management of their associated toxicities poses challenges for clinicians and researchers. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published from January 1, 2000, to October 15, 2022, and in the databases. A random-effects model with logit transformation was applied to the analysis heterogeneity between studies was evaluated using the I2 statistic with incidence and 95 % confidence interval (CI) for any adverse events (AEs), and serious AEs (SAEs). Results: In Crohn's disease (CD), the total AE incidence was 67.0 % (95 % CI, 66.2%–67.8 %; I2 = 97.2 %) for any AEs and 7.3 % (6.9–7.7; 97.2) for serious AEs. In ulcerative colitis (UC), the overall incidence of any and serious AEs was 63.6 % (63.0–64.3; 98.1) and 5.7 % (5.4–6.0; 88.9), respectively. The most common AEs were infections (21.5 [20.3–22.8], 32.6 [31.0–34.2], 25.9 [24.5–27.2], and 13.7 [10.7–16.7]) in CD patients that were treated with TNF antagonists, anti-integrins, anti-IL agents, and JAK inhibitors, respectively, and in UC patients also were infections (22.8 [21.7–24.0], 27.4 [25.9–28.9], and 18.4 [16.7–20.2]), respectively, as well as increases in lactic dehydrogenase levels (23.1 [20.8–25.4]) with JAK inhibitors. Conclusion: This study offers a comprehensive summary of toxic side effects of IBD treatments and a useful reference for both patients and clinicians.

Abstract The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments.

Objectives To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE. Methods In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. Results A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of these, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls; four were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (interquartile range [IQR] 8.3–23.3) years for cases and 12.4 (IQR 7.2–13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, P  = 0.028) and failed B cell depletion more frequently (75.0% vs 0%). Conclusion In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis and low response to anti-CD 20 therapy, potentially requiring a tailored treatment. [ABSTRACT FROM AUTHOR]

Objective To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA. Methods The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg once every 2 weeks (q2w) for at least 264 weeks up to 516 weeks (EXTEND: Sarilumab Monotherapy and Sarilumab + csDMARD groups) or for 276 weeks (MONARCH OLE: Continuation and Switch groups). Primary endpoints included safety, immunogenicity and changes in laboratory parameters. Secondary endpoints included clinical signs and symptoms along with health-related quality-of-life (HRQOL) questionnaires. Results The Sarilumab Monotherapy (n  =   111), Continuation (n  =   165) and Switch (n  =   155) groups received sarilumab monotherapy, while the Sarilumab + csDMARD group (n  =   1910) received sarilumab in combination with csDMARDs. Incidence of one or more treatment-emergent adverse events was 126 (Sarilumab Monotherapy group), 169 (Sarilumab + csDMARD group), 159 (Continuation group) and 159 (Switch group) events/100 patient-years. Neutropenia was the most common adverse event. Neutropenia was not associated with an increased incidence of infections. Most neutropenia cases normalized on-treatment. Adverse events of special interests, such as malignancies, major adverse cardiovascular events, venous thromboembolism and gastrointestinal perforations, were rare. Immunogenicity was low and not associated with hypersensitivity reactions or discontinuations due to lack or loss of efficacy. Improvements in clinical signs and symptoms and HRQOL, observed during the initial blinded trials, were maintained throughout the OLE assessment period. Conclusions Long-term sarilumab treatment with/without csDMARDs in patients with RA revealed no new safety findings. Efficacy and HRQOL were maintained or further increased over the open-label assessment period. Trial registration EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652 , NCT01146652; MONARCH OLE, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02332590 , NCT02332590 [ABSTRACT FROM AUTHOR]

Over the last few years, substantial progress has been made in the management of acute myeloid leukemia (AML). The first changes in the management of AML date back to last 2000s with the advent of hypometilant agents, later with Bcl2 inhibitor venetoclax, and Fms-like tyrosine kinase 3 (FLT3) inhibitors (midostaurin and gilteritinib), and more recently with IDH1/2 inhibitors (ivosidenib and enasidenib) and the hedgehog (HH) pathway inhibitor glasdegib. Glasdegid, formerly PF-04449913 or PF-913, acts as a smoothened (SMO) inhibitor and has been recently approved in combination with low-dose cytarabine (LDAC) by FDA and EMA for the treatment of naïve AML patients unfit for intensive chemotherapy. Several studies have explored the efficacy and safety of glasdegib, as a single agent or in combination with other drugs, in both the setting of relapsed/refractory and naïve AML patients, confirming its efficacy in controlling disease and safety profile. All these trials suggest that glasdegib seems to be an ideal partner for both classic chemotherapy and biological treatments (such as therapy with FLT3 inhibitors). Further studies are needed to better understand which patients are more likely to respond to glasdegib. [ABSTRACT FROM AUTHOR]

Background: Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. Methods: Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. Results: Children in the palmoplantar group were more likely to be male (p =.04), with an earlier age of psoriasis onset (p <.001), and more frequent nail involvement (p <.001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p =.004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p =.01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p =.01), and disease remission was less frequent (p =.05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p <.001). Conclusions: This study demonstrated the treatment‐resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines. [ABSTRACT FROM AUTHOR]

Luca Potestio,&ast; Fabrizio Martora,&ast; Gabriella Fabbrocini, Teresa Battista, Matteo Megna Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy&ast;These authors contributed equally to this workCorrespondence: Fabrizio Martora, Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy, Tel +39 081 7462457, Fax +39 081 7462442, Email fabriziomartora92@libero.itAbstract: The introduction of biologic drugs revolutionized the treatment of psoriasis, shifting treatment goals to higher treatment outcomes and less frequent safety issues. The outbreak of Coronavirus disease 2019 (COVID-19) represented a worldwide challenge, strongly affecting lifestyle, global economy, and overall health. Among the strategies adopted to contain the spreading of the infection, vaccination is the main one. In this context, the introduction of COVID-19 vaccines raised several doubts about their effectiveness and safety in patients undergoing therapy with biological for psoriasis. Even if molecular and cellular mechanisms by which COVID-19 vaccines lead to psoriasis development have not yet been fully elucidated, vaccination itself can trigger the release of interleukin (IL)-6, interferon (IFN) and tumor necrosis factor (TNF) α by T-helper (Th)1/Th17 cells. All these cytokines are involved in psoriasis pathogenesis. Thus, the aim of this manuscript is to review current literature on the safety and effectiveness of COVID-19 vaccination in psoriasis patients undergoing treatment with biologics, in order to clarify any concerns.Keywords: psoriasis, COVID-19 vaccinations, biologic therapies, efficacy, safety

Objectives The primary endpoint of the pivotal phase III study of infliximab (IFX) s.c. demonstrated non-inferiority of s.c. to i.v. IFX, based on 28-joint DAS-CRP (DAS28-CRP) improvement at week (W) 22 (NCT03147248). This post-hoc analysis investigated whether numerical differences in efficacy outcomes at W30/54 were statistically significant, using conservative imputation methods. Methods Patients with active RA and inadequate response to MTX received IFX i.v. 3 mg/kg at W0 and W2 (induction) and were randomized (1:1) to IFX s.c. 120 mg every 2 weeks or i.v. 3 mg/kg every 8 weeks thereafter (maintenance). Patients randomized to IFX i.v. switched to IFX s.c. from W30–54. This post-hoc analysis compared efficacy outcomes for s.c. and i.v. groups pre-switch (W30) and post-switch (W54) using last observation carried forward (LOCF) and non-responder imputation (NRI) methods. Results Of 343 randomized patients, 165 (IFX s.c.) and 174 (IFX i.v.) were analysed. At W30, significantly improved outcomes were identified with s.c. vs i.v. IFX for DAS28-CRP/DAS28-ESR/Clinical Disease Activity Index (CDAI)/Simplified Disease Activity Index (SDAI) scores (LOCF); ACR/good EULAR responses, DAS28-CRP/Boolean remission, and DAS28-CRP/DAS28-ESR/CDAI/SDAI low disease activity and remission (LOCF and/or NRI); and minimal clinically important difference in HAQ score (LOCF and NRI). After switching to IFX s.c. from IFX i.v. fewer significant between-group differences were identified at W54. Conclusion IFX s.c. showed improved efficacy at W30 compared with IFX i.v. and the reduced between-group difference in efficacy outcomes at W54 after switching supports the results suggesting benefits of IFX s.c. compared with IFX i.v. at W30. Trial registration ClincialTrials.gov, http://clinicaltrials.gov , NCT03147248, https://clinicaltrials.gov/ct2/show/NCT03147248. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of additionally given MTX on biologic treatment of polyarticular JIA in terms of effectiveness, safety and drug survival. Methods Patients suffering from polyarticular JIA and treated with either monotherapy with a first biologic or a combination of a biologic and MTX were selected from the BIKER registry. The TNF-α inhibitors (TNFi) adalimumab, etanercept and golimumab and the IL-6 inhibitor tocilizumab were considered. Upon a non-randomized study design, we adjusted the different cohorts using propensity score matching to improve comparability. Results A total of 2148 patients entered the analysis, who were treated by either combination therapy (n  = 1464) or monotherapy (n  = 684). Disease activity declined significantly more in patients upon combination therapy than upon biologic monotherapy. Comparison of adjusted cohorts revealed that patients who received TNFi gained more benefit from additionally given MTX than patients treated with tocilizumab. Median survival time of therapy with biologics was significantly longer upon combination therapy (3.1 years) than with monotherapy (2.7 years), as demonstrated by a Kaplan–Meier analysis (log rank test: P  = 0.002). The safety profile was moderately affected by additional MTX due to increased incidence of gastrointestinal and hepatic adverse events. Serious adverse events occurred at an equal rate of 3.6 events per 100 patient-years in both cohorts. Conclusion Additionally given MTX improves the effectiveness of biologic treatment in polyarticular JIA without seriously compromising treatment safety. Especially TNFi benefit from combination, while no improvement in outcome has been observed by combining tocilizumab with MTX. [ABSTRACT FROM AUTHOR]

Harpreet Singh,1 Liam Wilson,2 Tom Tencer,3 Jinender Kumar3 1Health Economics & Market Access (HEMA), Amaris Consulting Ltd, Toronto, ON, Canada; 2Health Economics & Market Access (HEMA), Amaris Consulting Ltd, Shanghai, People’s Republic of China; 3Bristol Myers Squibb, Princeton, NJ, USACorrespondence: Jinender Kumar, Global HEOR, Bristol Myers Squibb, 100 Nassau Park Blvd &num;300, Princeton, NJ, 08540, USA, Tel +1-609-302-7630, Email Jinender.Kumar@bms.comBackground: Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching.Objective: We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib.Methods: We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017− 2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching.Results: In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20– 95% (1.8– 36 months), clinical remission rates were 10– 94% (1.8– 36 months), colectomy rates were 0– 33% (12– 38 months), and adverse event rates were 0– 18%. Treatment switching rates in 21 studies were 4– 70% over 3– 62 months, with switch due to loss of response rates of 4– 35% over 12– 62 months (7 studies). Up to 35% of patients underwent colectomy 12− 120 weeks after switching, and 13– 38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching.Conclusion: Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.Keywords: ulcerative colitis, real-world evidence, systematic literature review, biologic therapies, tofacitinib

Objectives In patients with RA treated with (ultra-)low-dose rituximab (RTX), we investigated the association of dosing and timing of RTX on seroconversion after a third coronavirus disease 2019 (COVID-19) vaccination and the persistence of humoral response after a two-dose vaccination. Material and methods In this monocentre observational study, patients from the COVAC cohort were included in the third vaccine analysis if humoral response was obtained 2–6 weeks after a third vaccination in previous non-responders and in the persistence analysis if a follow-up humoral response was obtained before a third vaccination in previous responders. Dichotomization between positive and negative response was based on the assay cut-off. The association between the latest RTX dose before first vaccination, timing between the latest RTX dose and vaccination and response was analysed with univariable logistic regression. Results Of the 196 patients in the cohort, 98 were included in the third vaccine analysis and 23 in the persistence analysis. Third vaccination response was 19/98 (19%) and was higher for 200 mg RTX users [5/13 (38%)] than for 500 and 1000 mg users [7/37 (19%) and 7/48 (15%), respectively]. Non-significant trends were seen for higher response with lower dosing [200 vs 1000 mg: odds ratio (OR) 3.66 (95% CI 0.93, 14.0)] and later timing [per month since infusion: OR 1.16 (95% CI 0.97, 1.35)]. Humoral response persisted in 96% (22/23) and 89% (8/9) of patients who received RTX between the two measurements. Conclusions Repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy. A once positive humoral response after COVID-19 vaccination persists irrespective of intercurrent RTX infusion. Study registration. Netherlands Trial Registry (https://www.trialregister.nl/), NL9342. [ABSTRACT FROM AUTHOR]

Objectives The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). Methods Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. Results Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaïve) and 1948 with secukinumab (11% bionaïve). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9–6.3), compared with 1.7% (IR 2.3; 1.7–3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39–0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. Conclusion When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication. [ABSTRACT FROM AUTHOR]

The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases. [ABSTRACT FROM AUTHOR]

To analyse factors involved in the decision to optimise biologics in juvenile idiopathic arthritis. A "discrete-choice" methodology was used. In a nominal group meeting, factors which may influence physicians' decisions to optimise biological dose were identified, together with decision nodes. 1000Minds® was used to create multiple fictitious clinical scenarios based on the factors identified, and to deploy surveys that were sent to a panel of experts. These experts decided for each item which of two clinical scenarios prompted them to optimise the dose of biologic. A conjoint analysis was carried out, and the partial-value functions and the weights of relative importance calculated. In the nominal group, three decision nodes were identified: (1) time to decide; (2) to maintain/reduce or prolong interval; (3) what drug to reduce. The factors elicited were different for each node and included patient and drug attributes. The presence of macrophage activation syndrome (MAS), systemic involvement, or subclinical inflammation made the decision easier (highest weights). The presence of joints of difficult control and year of debut influenced the decision in some but not all, and in different directions. Immunogenicity, adherence, and concomitant treatments were also aspects taken into account. The decision to optimise the dose of biological therapy in children and youngster can be divided into several nodes, and the factors, both patient and therapy-related, leading to the decision can be detailed. These decisions taken by experts may be transported to practice, study designs, and guidelines. [ABSTRACT FROM AUTHOR]

Background: Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Healthcare professionals and patients in these populations should be alerted regarding the high risk of cardiovascular (CV) events and thus, customize the treatment strategy accordingly. Objective: This systematic literature review aimed to determine the effects of biological therapies on serious CV events in AS and PsA. Methods: Screening for the study was carried out using PubMed and Scopus databases from the database's inception to the 17th of July 2021. The literature search strategy for this review is based on the Population, Intervention, Comparator, Outcomes (PICOs) framework. Randomized controlled trials (RCTs) of biologic therapies for the treatment of AS and/or PsA were included. The primary outcome measure was the number of serious CV events reported during the placebo-controlled phase. Results: 4,422 articles were generated from keywords, eligibility criteria, and databases. Following the screening, we retained 13 studies for analysis: 3 in AS and 10 in PsA. Meta-analysis of results was not feasible due to the small number of the identified studies, the heterogeneity of the biologic treatment and the included populations, as well as the infrequently reported requested endpoint. According to our review, biologic treatments are safe options as for CV risk in patients with PsA or AS. Conclusion: Further and more extensive trials in AS/PsA patients at high risk of CV events are needed before firm conclusions can be drawn. [ABSTRACT FROM AUTHOR]

As our understanding of the pathogenesis of psoriasis has evolved over the past two decades, so has the number of treatment options. The introduction of biologic agents targeting specific cytokines in the interleukin (IL)-23/IL-17 pathway has proven successful in promoting skin clearance among patients. However, their use is often limited owing to cost, parenteral administration, and possible reduced efficacy over time. Topical therapies have also seen limited advancement, with agents such as corticosteroids and vitamin D derivatives remaining the mainstay of treatment, despite side effects limiting their long-term use. New therapeutic agents are needed to improve disease management for patients. In this review, we summarize pipeline and recently approved therapies undergoing clinical trials for psoriasis during a 12-month search period (30 June 2021 to 30 June 2022) using ClinicalTrials.gov. New-generation biologics and oral small molecules in phase II or III development were included, and pivotal data identified through various search modalities (PubMed, conference presentations, etc.) evaluating each drug candidate will be discussed. Topical therapies will also be discussed in line with recent US Food and Drug Administration approvals. As new therapies continue to enter the treatment landscape, long-term data and comparative trials will be needed to better understand their place among existing therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Since SARS‐CoV2 vaccines were approved without enough long‐term monitoring due to emergent situations, some issues have been raised about timing and protocol of receiving them by patients treated by different immunosuppressive agents. Aim and Method: Here, we present different aspects of SARS‐CoV‐2 vaccination in such patients in the field of dermatology. Result: In brief, SARS‐CoV‐2 vaccination is recommended in all dermatologic patients, regardless of their disorders and therapeutic regimens. Nevertheless, special considerations should be given to the immunosuppressive therapy and its association with vaccination timing due to the decreased immunogenicity of vaccines in this setting. Conclusion: Novel biologic immunotherapies are advantageous over conventional systemic therapies not only in their safety and selective functions but also in this aspect that many of them do not affect vaccines immunogenicity. [ABSTRACT FROM AUTHOR]

Combined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We evaluated the use of combinations of conventional systemic therapies and biologics in children with psoriasis in daily practice. This two‐part study used data from the 170 children in the Franco‐Italian BiPe cohorts to evaluate the use, efficacy, and safety of combined conventional systemic–biologic therapies, and from a survey carried out among French and Italian dermatologists to better understand the reasons for using or avoiding these combinations. In total, 33 children (19.4%) from 13 dermatology centers received 48 combined conventional systemic–biologic therapies (cumulative duration: 43.6 years), including three triple combination therapies (acitretin–methotrexate, with a TNF‐alpha inhibitor). A total of 14 different combinations were used, most frequently etanercept–acitretin (n = 10), adalimumab–acitretin (n = 7), adalimumab–methotrexate (n = 5), and ustekinumab–methotrexate (n = 5). The combined therapies were started at biologic initiation in 41 cases (85.4%), and after a period of biologic monotherapy in the remaining 7 cases. Mean PGA and PASI scores decreased between baseline and M3 with all the combinations used. Four serious adverse events were reported, all with favorable outcomes. The survey was completed by 61 dermatologists: 39 (63.9%) had previously used or planned to use the combined therapies, most commonly TNF‐alpha inhibitors with acitretin or methotrexate. The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. Combined therapies have been used frequently in the treatment of childhood psoriasis, in a range of clinical situations and in variable drug combinations, without significant toxicity. Although the use of these combined therapies needs to be clarified in future management guidelines, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis, and recalcitrant disease. [ABSTRACT FROM AUTHOR]

Objectives Adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) could be at risk for disease flare secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or to withholding anti-inflammatory therapy. While vaccination can protect against coronavirus disease 2019 (COVID-19), safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRDs are limited. This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRDs, 80% of whom are on chronic immunomodulatory therapy. Methods Vaccine side effects, disease activity and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls 2–9 weeks after the second dose. Results A total of 91 patients and 40 healthy controls were included. The safety profile was good, with 96.7% (n  = 88) of patients reporting mild or no side effects and no change in disease activity. However, three patients had transient acute symptoms: two following the first vaccination (renal failure and pulmonary haemorrhage) and one following the second dose (mild lupus flare vs viral infection). The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls [242 (s. d. 136.4) vs 387.8 (57.3) BAU/ml, respectively; P  < 0.0001]. No cases of COVID-19 were documented during the 3 month follow-up. Conclusion Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy and a high seropositivity rate but lower anti-S1/S2 antibody titres compared with healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRDs, even while on immunomodulation. [ABSTRACT FROM AUTHOR]

Background: Biologic therapies are often used in patients with ulcerative colitis (UC) who are nonresponsive to conventional treatments. However, nonresponse or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with UC in the USA. Methods: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with UC initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N = 1,291], infliximab [N = 810], golimumab [N = 127], and vedolizumab [N = 103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred USD 20,106 higher total UC-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration = 112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with UC initiating biologic therapies. Suboptimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients. [ABSTRACT FROM AUTHOR]

Objectives To investigate the knowledge and beliefs of Australian patients with inflammatory arthritis regarding biologic/targeted synthetic DMARDs (b/tsDMARDs) and biosimilars and their sources of information. Methods Participants enrolled in the Australian Rheumatology Association Database (ARAD) with RA, PsA and axial SpA were sent an online survey. They were asked about information sources for b/tsDMARDs and how positive or negative this information was. The Beliefs about Medicine Questionnaire (BMQ) was used to measure beliefs about b/tsDMARDs with scores ranging from 1 (strongly disagree) to 5 (strongly agree). Participants were asked about their knowledge of biosimilars and willingness to switch to biosimilar. Results There was a response rate of 66% (994/1498; 67% female, median age 62 years). Participants currently taking b/tsDMARDs (n  = 794) had a high b/tsDMARD-specific BMQ 'necessity' score {median 4.2 [interquartile range (IQR) 3.6–4.8]}, with a lower specific 'concerns' score [median 2.4 (IQR 2.0– 3.0)]. Participants consulted multiple information sources [median 3 (IQR 2–5)]. Positive sources were rheumatologists and educational websites and negative were chat rooms and social media. Only 18% were familiar with biosimilars, with half knowing of availability in Australia. Following a short paragraph describing biosimilars, 75% (744) of participants indicated they would consider switching if recommended by their rheumatologist, with nearly half identifying safety and efficacy of biosimilars as an important concern. Conclusion Australian patients have positive attitudes towards b/tsDMARDs overall, although little knowledge of biosimilars specifically. They have a high degree of trust in their rheumatologist regarding treatment decisions, even if they are unfamiliar with the medication recommended. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common chronic condition characterized by nasal congestion, sneezing, and itching, which significantly impacts quality of life. Traditional treatments, including antihistamines and intranasal corticosteroids, often fall short in managing moderate-to-severe cases. Recently, biologic therapies such as omalizumab and dupilumab have emerged as potential alternatives. This systematic review aims to evaluate the efficacy and safety of these biologic therapies in the management of AR. A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science to identify studies published between 2000 and 2024. Studies included were randomized controlled trials, cohort studies, and post-hoc analyses that assessed the impact of biologics on AR symptoms. Data on study characteristics, population demographics, intervention details, and outcomes were extracted and analyzed. The review included nine studies evaluating omalizumab and dupilumab. Omalizumab demonstrated significant improvements in nasal symptoms and quality of life, with notable efficacy in reducing symptoms and improving asthma control in patients with moderate-to-severe AR. Dupilumab also showed positive outcomes, particularly in patients with comorbid asthma and perennial AR, by reducing severe exacerbations and improving symptom scores. Biologic therapies, including omalizumab and dupilumab, offer promising alternatives for the management of AR, especially in cases that are severe or refractory to conventional treatments. The evidence supports their efficacy in improving symptoms and quality of life. Nevertheless, further research is required to address the limitations identified, including the need for long-term data and clarification of the mechanisms of action. These findings underscore the potential of biologics in advancing the treatment of AR and highlight the importance of ongoing research to optimize patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yamani et al.)

Introduction: Therapeutic Drug Monitoring (TDM) has an important role in the management of inflammatory bowel disease (IBD) patients on infliximab (IFX) or adalimumab and is recommended in IBD patients presenting a loss of response under anti TNF agent. But, TDM was not recommended for others biotherapies., Areas Covered: Analyzing all publications about TDM and biologics in IBD patients, we reported the major results for each biotherapy., Expert Opinion: Emerging data suggest that TDM will probably be similarly useful forIFX SC. In contrast, there is no demonstrated clinical benefit to the use of TDM with golimumab. For vedolizumab results for the use of both reactive and proactive TDM are discordant. For ustekinumab, data supports the existence of an exposure response relationship, albeit of a lesser magnitude than with anti-TNF agents. Finally, recent data from small case series suggests that TDM could be valuable in optimizing anti-IL23 agents, particularly risankizumab, but this requires further clarification. Consistent with the new concept of 'proactive' strategy, recent data support the utility of dashboard-driven model informed precision dosing (MIDP) of anti-TNF agents, in particular infliximab. Dashboards are software systems using Bayesian population pharmacokinetic modelling to individualize recommendations for target drug levels.

The role of gut microbiota in influencing the efficacy and side effect profile of biological therapies for autoimmune diseases has gained increasing attention. Understanding these interactions is crucial for optimizing treatment outcomes and minimizing adverse events associated with biological therapies. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively analyzed studies involving human subjects with autoimmune diseases treated with biological therapies. Data on gut microbiota composition, therapeutic efficacy, and side effect profiles were extracted and synthesized to assess the impact of microbiota on treatment outcomes. Our review identified a significant relationship between gut microbiota composition and the efficacy of biological therapies. Specific bacterial taxa, such as Clostridiales and Roseburia inulinivorans , were associated with improved therapeutic responses, while alterations in microbiota were linked to increased adverse events. The predictive potential was demonstrated with microbiota signatures correlating with treatment success and side effects, highlighting the relevance of microbial profiles in therapeutic outcomes. The findings suggest that gut microbiota plays a pivotal role in modulating the efficacy and side effect profile of biological therapies for autoimmune diseases. Integrating microbiota assessments into clinical practice could enhance personalized treatment strategies and improve patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Qusty et al.)

Background: Temporary eosinophilia is a potential adverse reaction of monoclonal antibody therapies in the treatment of a variety of type 2 inflammatory conditions, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). The pathophysiology, epidemiology, and clinical significance of eosinophilia and eosinophilic adverse reactions following the initiation of biologic therapy are unclear., Objectives: To describe the postmarketing, eosinophilic adverse reactions with clinical significance in patients treated with the 3 biologic therapies approved by the U.S. Food and Drug Administration (FDA) for CRSwNP: dupilumab, omalizumab, and mepolizumab., Methods: The FDA Adverse Event Reporting System (FAERS) Public Dashboard was searched for eosinophilic adverse reactions related to dupilumab, omalizumab, and mepolizumab treatments from November 2004 to December 2022. Data regarding each of the eosinophilic adverse reactions were extracted and analyzed., Results: A total of 218, 270, and 134 reports of eosinophilic adverse reactions were reported among patients who were treated with dupilumab, omalizumab, and mepolizumab, respectively. The most common eosinophilic adverse reaction was eosinophilic granulomatosis with polyangiitis (338 patients), followed by eosinophilic respiratory tract reactions (158 patients). The most common indication for biological treatment among the reaction groups was asthma., Conclusions: Eosinophilic adverse reactions are rare but consequential complications of biological treatment. They are more common among patients treated for asthma and chronic rhinosinusitis with nasal polyposis. Measuring and monitoring blood eosinophil levels may be appropriate in specific clinical instances when patients are started on different biologic therapies for type 2 inflammatory conditions., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurosarcoidosis, a manifestation of sarcoidosis affecting the central or peripheral nervous system, presents unique challenges in diagnosis and management. Neurosarcoidosis can manifest with a wide range of symptoms, including cranial neuropathies, seizures, meningitis, and cognitive impairments. The heterogeneity of presentations often leads to diagnostic delays and complications. Diagnosis relies on a combination of clinical features, neuroimaging, cerebrospinal fluid analysis, and evidence of systemic sarcoidosis. Recent advances in imaging techniques, including high-resolution MRI, positron emission tomography (PET) scans, and novel biomarkers, have improved diagnostic accuracy. However, distinguishing neurosarcoidosis from mimicking conditions such as multiple sclerosis remains challenging. Treatment typically begins with corticosteroids, often requiring long-term immunosuppression. Second-line agents such as methotrexate and mycophenolate mofetil are frequently used as steroid-sparing options. Biologic therapies, particularly Tumor necrosis factor-alpha (TNF-α) inhibitors like infliximab, have shown promise in refractory cases. The long-term management of neurosarcoidosis necessitates a multidisciplinary approach with regular monitoring of disease activity and treatment response. Despite advancements, significant knowledge gaps persist in understanding the etiology, pathophysiology, and optimal management of neurosarcoidosis. Future research directions include identifying specific biomarkers, developing targeted therapies, and exploring novel imaging techniques. The rarity and heterogeneity of neurosarcoidosis underscore the importance of multicenter studies and international collaborations to advance our understanding and improve patient outcomes. Emerging technologies and innovative therapeutic approaches offer promising avenues for enhancing diagnosis and treatment in the coming years., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sinha et al.)