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Background: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019. Methods: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD). Results: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD. Conclusion: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost‐awareness information for the Colombian health system. [ABSTRACT FROM AUTHOR]

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Background: Severe asthma is a challenging condition that often resists traditional treatments and requires high-dose inhaled corticosteroids and other controllers to manage uncontrolled symptoms. Recent advances include the use of biologic agents targeting specific inflammation pathways, which have improved symptom control and quality of life, although their effects on small airways remain less understood. Methods: This prospective observational study, conducted at Tor Vergata University Hospital in Rome from July 2021 to March 2024, aims to evaluate the efficacy of treatments in patients with uncontrolled severe asthma. It involves baseline assessments and follow-ups at 1 and 3 months post-biological therapy initiation, focusing on both spirometric and non-spirometric (oscillometry) measurements of the small airways to provide a comprehensive evaluation of respiratory function. Results: This study, conducted from July 2021 to March 2024, enrolled 40 patients with severe asthma, ultimately analyzing data from 31 participants who underwent biological therapy. The results showed significant improvements in asthma symptoms, the ACT scores increased significantly from visit 1 to visit 2 (p = 0.00008) and from visit 1 to visit 3 (p = 0.00047), and pulmonary function tests, with notable increases in FEV1 (from visit 1 (74.97 ± 23.43%) to visit 2 (82.96 ± 26.57%, p = 0.041) and to visit 3 (88.89 ± 31.41%, p = 0.003)) and quality of life scores, and substantial reductions in specific airway resistance and small airway dysfunction markers (the PEF, %pr post-BD showed significant improvement from visit 1 to visit 3 (p = 0.012)). However, oscillometric measurements showed no significant changes post-therapy. Conclusions: The study concluded that there was an improvement in the small airways measured by non-oscillometric values, without significant improvements in oscillometric parameters. Additionally, a significant improvement in symptoms was observed after the first month of therapy. There was also a significant increase in respiratory function after one to three months of therapy. [ABSTRACT FROM AUTHOR]

• RA patients face an increased risk of CV diseases due to systemic inflammation and disease activity. • Other than traditional CV risk factors in RA patients, systemic inflammation and autoantibodies contribute to the heightened CV risk. • RA patients have low TC, LDL, and HDL but still experience high rates of CV events, known as the "lipid paradox," due to increased cholesterol breakdown and altered HDL function from inflammation. • In RA patients, inflammatory markers like CRP and cytokines promote atherosclerosis. • Early and aggressive intervention with DMARDs is crucial in achieving clinical remission, and potentially lowering the risk of CV events in RA patients. Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients. [ABSTRACT FROM AUTHOR]

As the role of neurologists in managing patients with rheumatic diseases expands, collaboration between rheumatologists and neurologists becomes increasingly vital. This literature review provides an overview of the central nervous system (CNS) manifestations of major autoimmune rheumatic disorders, which may include parenchymal brain and meningeal disease (stroke, meningoencephalitis, meningitis), myelopathies, psychosis, chorea, seizure disorders, and various forms of cephalea. Novel findings linking specific autoimmune markers to CNS damage reveal a direct, previously underestimated link between systemic inflammation and neural injury. Besides, with the increasing use of biological therapies, it is crucial to recognize when neurological manifestations are related to adverse events of therapy, as this may significantly influence treatment decisions. Neurologists play a key role in this assessment, working closely with rheumatologists. Overall, addressing CNS involvement in rheumatic diseases is important for improving patient outcomes and advancing medical knowledge in this complex field. A thorough understanding of the neurologic aspects of rheumatic diseases is essential for optimal patient care, necessitating a multidisciplinary approach to management. [ABSTRACT FROM AUTHOR]

Recent research indicates that the microbiome has a significant impact on the progression of inflammatory bowel disease (IBD) and that creating therapies that change its composition could positively impact the outcomes of IBD treatment. This review summarizes the results of extensive studies that examined IBD patients undergoing several therapies, including anti-TNF medication, vedolizumab, ustekinumab, probiotics, and fecal microbiota transplantation (FMT), and the alterations in their gut microbiota's composition and function. The objective was to investigate the variety and effectiveness of microbial species in order to discover new biomarkers or therapeutic targets that could improve the outcome of treatment for these patients. This research aimed to offer useful insights into personalized medicine techniques for managing IBD. Beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia have been consistently linked to favorable clinical outcomes, whereas pathogenic bacteria such as Escherichia coli and Clostridioides difficile are associated with worsening disease conditions. Although many studies have examined the role of gut microbiota in IBD, there is still a need for more targeted research on the connection between specific microbial communities and treatment outcomes. This study sought to address this gap by exploring the intricate relationship between the gut microbiota composition and the effectiveness of IBD medications. [ABSTRACT FROM AUTHOR]

Objective To assess current evidence for effectiveness of sequential lines of biologic and targeted small-molecule disease-modifying anti-rheumatic drugs (b/tsDMARDs) when used beyond first-line for psoriatic arthritis (PsA). Methods A systematic search of the literature (Medline, Embase, bibliographic searches) was undertaken (October and December 2022) to find studies meeting the criteria of assessing effectiveness of b/tsDMARDs beyond first-line in adults with PsA (PROSPERO CRD42022365298). Risk of bias assessment was undertaken (ROBINS-I/Cochrane RoB2). Results Of 2666 abstracts identified and following a full text review of 177 psoriatic disease studies, 12 manuscripts and two abstracts were eligible. Of the 12 manuscripts, 11 were observational and one was a sub-analysis of a RCT (n  = 16 081: average age 49.5 years, female 53.3%). Two abstracts (n  = 7186) were included. All studies comparing first- and second-line (three studies) found a reduced response in second-line. On average, DAPSA remission (most reported outcome, eight studies) was achieved in 26%, 19% and 10% first-, second- and third-line TNFi, and 22%, 13% and 11% first-, second- and third-line other bDMARDs, respectively. Responses varied to third-line bDMARDs; four studies found comparable second- and third-line responses, five studies found diminishing responses in sequential lines. Conclusion Predominantly observational studies, inherently at high risk of bias, indicate bDMARDs can be effective to third-line in PsA, but that response is reduced after first line. There is very limited data for more advanced lines of b/tsDMARD. Prospective studies are required to better understand clinical response to advanced lines of treatment in PsA. [ABSTRACT FROM AUTHOR]

Anti-HMGCR myopathy is an increasingly recognized immune-mediated necrotizing myopathy. However, there are currently no evidence-based treatments available, so case reports and clinical experience are used to guide current management. We report a case of a 49-year-old man, treated with atorvastatin, who presented to the emergency department with progressive proximal muscle weakness. Anti-HMGCR antibodies were detected, and muscle biopsy revealed necrotizing myopathy. Initially, therapy with high-dose glucocorticoids and methotrexate was started, but 12 weeks later, the patient developed clinical deterioration with dysphagia. Then, he was successfully treated with one cycle of rituximab along with physical therapy. The use of rituximab in immune-mediated necrotizing myopathy has been heterogeneously described in the literature but mostly in case reports. The European Neuromuscular Centre working group recommends the use of rituximab in refractory cases. However, some studies highlight the importance of early and aggressive treatment for this disease. Clinical prospective studies are necessary to make proper evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Background Biological therapies are effective for psoriasis, but patient responses vary, often requiring therapy switching or discontinuation.Objectives To identify physicians’ prescribing patterns of biological therapies at a referral tertiary center in Saudi Arabia and assess the probability of biologic persistence following treatment initiation.Methods We conducted a retrospective study of biologic-naïve adult psoriasis patients who initiated therapy from October 2013 to July 2022 in Dammam. Descriptive statistics and a Kaplan-Meier analysis evaluated treatment persistence at 6, 12, 24, and 36 months.Results A total of 151 patients received adalimumab (n = 89), etanercept (n = 17), risankizumab (n = 30), ustekinumab (n = 14), and ixekizumab (n = 1). At 6 months, all therapies demonstrated 100% persistence. At 12 months, persistence was highest for ustekinumab (100%) and lowest for etanercept (88.2%). At 24 months, ustekinumab maintained 100% persistence, followed by risankizumab (96.6%), adalimumab (94.3%), and etanercept (76.4%). At 36 months, risankizumab had the highest persistence (96.6%), followed by adalimumab (83.1%), ustekinumab (78%), and etanercept (70.6%). The most common reasons for discontinuation were lack of effectiveness and intolerability.Conclusion This study shows changing psoriasis treatment patterns with new therapies. Risankizumab demonstrated high long-term persistence, while etanercept and ustekinumab showed declining persistence, suggesting evolving treatment considerations.

Background: In 2017, belimumab (BEL) was approved in subcutaneous (SQ) administration. The effectiveness after switching from intravenous (IV) to SQ and patient satisfaction in daily clinical practice has not been studied. During the pandemic, patient follow-up and treatment were significantly affected, and some patients need a change from IV to SQ. Our aim was to evaluate daily clinical practice satisfaction to SQ BEL therapy in patients previously treated IV BEL. We hypothesized that SQ BEL in SLE patients previously treated with IV BEL was similar in effectiveness and conferred higher satisfaction. Methods: Observational, multicenter study, conducted in 7 reference centers in Catalonia. We included stable SLE patients (EULAR/ACR 2019) on treatment with SQ BEL and previous use of IV BEL (at least 3 months on IV BEL before switching). Since there are no well-validated tools for SQ BEL treatment satisfaction, we used RASQ-SQ, validated in patients with lymphoma who switched from IV Rituximab to SQ treatment, and modified for BEL treatment. Results: Twenty-seven patients were included. The more prevalent clinical manifestations observed were related to the skin and joints and the patients had a mean baseline SLEDAI of 2.96 (SD 2.4) and SLICC score of 0.67 (SD 0.88). The median time from treatment with IV BEL before switching to SQ was 21 months (range). 84% of patients reported confidence in SQ BEL. 85.2% felt that treatment with SQ BEL was convenient or very convenient. 85% felt they had gained time with the change. 89% would recommend the SQ injection to other patients. Disease activity (mean SLEDAI) and remission rates remain stable after switching. No major new adverse effects were reported. Conclusions: Overall satisfaction, satisfaction with via of administration, and satisfaction with the time taken to receive BEL were higher for SQ BEL treatment. A switching SQ strategy is a reasonable alternative for BEL patients. [ABSTRACT FROM AUTHOR]

Objectives To explore prognostic and predictive markers of SSc-associated interstitial lung disease (SSc-ILD) outcomes in a phase 3 trial (focuSSced) and prognostic markers in a real-world cohort (SMART). Methods The focuSSced SSc-ILD subgroup included 68 of 106 placebo-treated and 68 of 104 tocilizumab-treated patients. The SMART cohort included 505 patients with SSc-ILD. Linear mixed-effect models were used to identify factors associated with change in forced vital capacity (FVC). Kaplan–Meier estimation and Cox regression were used for time-to-event analyses. Results In placebo-treated focuSSced patients, sex was a significant prognostic factor for FVC decline; males had increased risk for absolute decline ≥10% in percent-predicted FVC (ppFVC) and 0.22% faster weekly FVC decline than females (P   =  0.0001). FVC was 9.8% lower in patients with CRP >6 mg/ml vs those with CRP ≤6 mg/ml (P  = 0.0059). Tocilizumab reduced the risk for ≥10% decline in ppFVC in patients who were male, had earlier disease (<2 years duration), had IL-6 levels <10 pg/ml, or had anti-topoisomerase antibodies (ATA). In the SMART cohort, prognostic factors for ppFVC <70% were male sex, ATA, and low baseline FVC. Males had 3.3% lower FVC 1 year after disease onset (P  < 0.001) and 0.6% faster yearly decline (P  = 0.03) than females. Conclusion Prognostic markers in SSc-ILD were similar between focuSSced and SMART. Male sex and inflammatory markers were associated with lower FVC but IL-6 ≥10 pg/ml was not predictive of response to tocilizumab. Trial Registration ClinicalTrials.gov: NCT02453256. [ABSTRACT FROM AUTHOR]

Background: The transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options. Methods: We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded. Results: Four hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced. Conclusion: The transition from in-hospital to subcutaneous therapeutic management of biological therapy at home was generally viewed favorably by patients, especially if they have commitments or were residents far from the IBD center. [ABSTRACT FROM AUTHOR]

Introduction: The participation of immune components in inflammatory skin pathologies has brought about the possibility of intervening in the processes that trigger or perpetuate them, hence the importance of knowing the various biological therapies that target specific proteins that They are the result of dysfunction of the immune response in several skin diseases. In the present review work, various aspects related to the selection criteria of biological products (or biopharmaceuticals) are presented with particular interest in monoclonal antibodies (mAb) as well as the main dermatological pathologies in which they have been applied. This is due to the fact that the use of mAbs has been used mainly in the therapy of neoplasias and the possibility of their use in other skin conditions in addition to cancer is being explored. Development of the topic: This bibliographic review addresses the main aspects related to: a) Safety and immunogenicity of monoclonal antibodies, b) Therapeutic applications of mAbs in dermatology: Psoriasis, Atopic dermatitis, Hidrandenigtis suppurativa, Urticaria, Pemphigus, Alopecia areata, Pyoderma gangrenosum Pityriasis nubra pilaris, Cutaneous sarcoidosis, Behcet's syndrome and other pathologies, c) Biosimilars in dermatology and d) Skin lesions associated with the use of monoclonal antibodies. Discussion: mAb-based therapeutics is an area of constant growth and recombinant technology has allowed the obtaining of increasingly stable and less immunogenic molecules that will allow us to offer therapeutic options for various dermatological pathologies with characteristics of hyperinflammation or immunosuppression. Conclusion: The increase in clinical studies for the potential use of monoclonal antibodies in dermatology will allow their authorization by regulatory agencies and increase the therapeutic arsenal for conditions that are difficult to control. [ABSTRACT FROM AUTHOR]

Background & objectives: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs’: TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. Patients & methods: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). Results: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation.Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. Conclusions: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Abstract Background Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreased availability of intravenous tocilizumab during the COVID-19 pandemic, we started using the subcutaneous formulation of the drug in children with anti-TNF refractory uveitis. The study analyzes the serum concentration of tocilizumab and its clinical response in patients with anti-TNF refractory uveitis who started or switched to subcutaneous administration from intravenous use. Methods Five patients with non-infectious uveitis were treated with subcutaneous tocilizumab. Ocular inflammation was evaluated on slit lamp examination during clinical control. Serum tocilizumab concentrations were determined by ELISA. Results The mean blood concentration of tocilizumab was 61.4 µg/mL (range 2.7–137.0.), with higher values than levels recorded in adult patients with rheumatoid arthritis treated with intravenous tocilizumab. Three patients entered clinical remission. One patient developed a mild relapse and was treated with topical steroids. Only one patient did not respond to therapy. The medication was well tolerated without severe infection or other adverse events. Conclusion Our results support a possible role of subcutaneous tocilizumab in anti-TNF refractory uveitis.

A triad of symptoms characterises Felty's syndrome: seropositive rheumatoid arthritis (RA), splenomegaly and neutropenia. The treatment of Felty's syndrome is based on using classic synthetic and biological disease-modifying drugs (DMARDs). In this article, we present a case of a patient with Felty's syndrome who was treated with biologic treatment. A systematic search of the literature on the electronic medical database was conducted. The drugs from the DMARD group, despite reducing the activity of the disease, may cause significant clinical complications. It is important to know about the diagnosis, differentiation and treatment of neutropenia and the prevention of febrile neutropenia. The article discusses the current therapeutic possibilities using both classical and biologic DMARDs.

Ana Neves,1 Luísa Viveiros,2 Veronica Venturelli,3 David A Isenberg4 1Internal Medicine Department, Centro Hospitalar Universitário de São João, Oporto, Portugal; 2Internal Medicine Department, Centro Hospitalar Universitário de Santo António, Oporto, Portugal; 3Rheumatology Unit, Department of Medical Sciences, Università degli Studi di Ferrara, Azienda Ospedaliero-Universitaria S. Anna, Cona, Italy; 4Centre for Rheumatology, Department of Medicine, University College London, London, UKCorrespondence: David A Isenberg, The Department of Rheumatology, Division of Medicine, University College London, Room 423 the Rayne Building, London, WC1E 6JF, UK, Email d.isenberg@ucl.ac.ukAbstract: Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients’ quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoints in both general SLE and LN, with only two biological drugs (belimumab and anifrolumab) being approved by the Food and Drug Administration (FDA) for the treatment of SLE. Recently, several Phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in LN, and some of them have demonstrated an improvement in clinical and laboratory measures. Multi-target therapies are also being successfully developed and encourage a belief that there will be an improvement in LN outcomes.Keywords: biological therapies, systemic lupus erythematosus, lupus nephritis, trial

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation and progressive fibrosis, typically affecting the skin, with variable internal organ involvement. Interstitial lung disease (ILD), with a prevalence between 35 and 75%, is the leading cause of death in patients with SSc, indicating that all newly diagnosed patients should be screened for this complication. Some patients with SSc-ILD experience a progressive phenotype, which is characterized by worsening fibrosis on high-resolution computed tomography (HRCT), a decline in lung function, and premature mortality. To assess progression and guide therapeutic decisions, regular monitoring is essential and should include pulmonary function testing (PFT), symptom assessment, and repeat HRCT imaging when indicated. Multidisciplinary discussion allows a comprehensive evaluation of the available information and its consequences for management. There has been a shift in the approach to managing SSc-ILD, which includes the addition of targeted biologic and antifibrotic therapies to standard immunosuppressive therapy (particularly mycophenolate mofetil or cyclophosphamide), with autologous hematopoietic stem-cell transplantation and lung transplantation reserved for refractory cases. [ABSTRACT FROM AUTHOR]

Background: The study aimed to explore influenza antibody response in patients with autoimmune inflammatory rheumatoid diseases (AIIRDs) stratified by the different vaccine types applied in Denmark during the 2018-2019 influenza season. Methods: Included patients were diagnosed with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis receiving biological disease-modifying antirheumatic drugs (bDMARDs) with or without conventional synthetic disease-modifying antirheumatic drugs. Influenza vaccination status in the 2018-2019 season and vaccine type received were reviewed in the Denmark. Blood samples were drawn ≥ 14 days post vaccination, and antibody titers were determined by the hemagglutinin inhibition (HAI) assay for the serotypes A/Michigan/H1N1, A/Singapore/H3N2, and B/Colorado included in the influenza vaccines in the 2018--2019 season. An overall serotype HAI geometric mean titer (GMT) was calculated from the 3 serotype-specific HAI titers. An overall serotype HAI GMT ≥ 40 was considered protective. Results: Of the 205 included patients, 105 (51%) had received influenza vaccination. One-quarter of vaccinated patients achieved post-vaccination overall serotype HAI GMT ≥40. For patients vaccinated with Influvac, a significantly higher proportion had HAI titers ≥ 40 for 2 serotypes, namely, A/Michigan/H1N1 and A/Singapore/H3N2, than patients vaccinated with Vaxigrip or VaxigripTetra. The same applied to all serotypes HAI GMT, where significantly more patients who received Influvac achieved postvaccination HAI GMT≥40 versus patients who received Vaxigrip (p=0.02) or VaxigripTetra (p=0.002). The latter outcome was explored in a multivariable logistic regression analysis and remained significant when including the following variables: age, sex, treatment with methotrexate and/or prednisolone, type of influenza vaccine, time interval from vaccination to antibody measurement, and previous vaccination status. Conclusion: Influenza antibody levels following vaccination with Influvac in bDMARD-treated patients with AIIRDs were superior to Vaxigrip and VaxigripTetra. Treatment with methotrexate (MTX) did not reduce the antibody response. [ABSTRACT FROM AUTHOR]

Background: According to the current 2009 Assessment in SpondyloArthritis international Society (ASAS) classification criteria, ankylosing spondylitis (AS) is classified as radiographic axial inflammatory spondyloarthropathy. AS is a chronic, progressive inflammatory disease involving primarily the spine and sacroiliac joints, less commonly the peripheral joints, tendinous attachments and internal organs. According to current ASAS and European Alliance of Associations for Rheumatology (EULAR) recommendations, optimal treatment of AS patients needs a combination of pharmacotherapy and nonpharmacological treatment, based on education and rehabilitation treatment. Modern pharmacotherapy for AS, based on anticytokine therapy (biologics), significantly reduces the clinical activity of the disease, reduces active inflammation and inhibits radiographic progression. The aim of this study is to evaluate the effect of physical therapy on functional status, disease activity and quality of life in AS patients treated with biologics. Material and methods: The study included fifty active AS patients treated with biologics, who were randomly allocated to two groups. Group I patients, in addition to treatment with a tumor necrosis factor alpha (TNF-α) inhibitor, received a course of physical therapy twice with a 6-month interval, which consisted of hydro-air massage and rehabilitation exercises. Group II patients were treated with a TNF-α inhibitor only. In both groups, the study lasted 10 months. At follow-up visits, all participants underwent a physical examination, laboratory tests and the following questionnaire-based studies: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Short Form Health Survey (SF-36) v.2. Results: The applied physical therapy programme did not improve physical performance in the patients studied. There was no improvement in any of the physical parameters studied. Therefore, the functional status did not improve and disease activity did not decrease in the patients studied. However, some domains from the quality-of-life assessment improved. Conclusions: Physical therapy and education should be the primary form of non-pharmacological treatment in AS patients treated with biologics. [ABSTRACT FROM AUTHOR]

Objective. The goal of juvenile idiopathic arthritis ( JIA) treatment is to maintain clinical remission. It is also important to reduce drug exposure, whenever possible, in order to avoid or decrease potential side effects. We aimed to analyze remission survival after systemic treatment withdrawal and to determine which factors can influence it. Methods. We conducted a multicenter, observational, longitudinal study. All patients included had a diagnosis of JIA. We analyzed remission survival using Kaplan-Meier curves according to the systemic treatment received (methotrexate [MTX] alone or in combination with biologic disease-modifying antirheumatic drugs [bDMARDs]) and JIA subgroups (oligoarticular and polyarticular course, juvenile spondyloarthritis, and systemic JIA). In addition, risk factors were examined using multivariate analysis. Results. We included 404 patients with JIA; 370 of them (92%) had received systemic treatment at some point and half of them (185 patients) had withdrawn on at least 1 occasion. There were 110 patients who flared (59%) with a median time of 2.3 years. There were no differences in remission survival between JIA subcategories. Twenty-nine percent of patients with JIA who received MTX and bDMARDs, in which MTX alone was withdrawn, flared; median time to flare of 6.3 years. However, if only the bDMARD was withdrawn, flares occurred 57% of the time; median time to flare of 1.1 years. Conclusion. Flares are frequent when systemic treatment is withdrawn, and uveitis or joint injections could be related risk factors. In MTX and biologic-naïve patients, the frequency of flares occurred in more than half of patients, although they were less frequent when clinical remission lasted for > 1 year. [ABSTRACT FROM AUTHOR]

Background: Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreased availability of intravenous tocilizumab during the COVID-19 pandemic, we started using the subcutaneous formulation of the drug in children with anti-TNF refractory uveitis. The study analyzes the serum concentration of tocilizumab and its clinical response in patients with anti-TNF refractory uveitis who started or switched to subcutaneous administration from intravenous use. Methods: Five patients with non-infectious uveitis were treated with subcutaneous tocilizumab. Ocular inflammation was evaluated on slit lamp examination during clinical control. Serum tocilizumab concentrations were determined by ELISA. Results: The mean blood concentration of tocilizumab was 61.4 µg/mL (range 2.7–137.0.), with higher values than levels recorded in adult patients with rheumatoid arthritis treated with intravenous tocilizumab. Three patients entered clinical remission. One patient developed a mild relapse and was treated with topical steroids. Only one patient did not respond to therapy. The medication was well tolerated without severe infection or other adverse events. Conclusion: Our results support a possible role of subcutaneous tocilizumab in anti-TNF refractory uveitis. [ABSTRACT FROM AUTHOR]

Premature Ovarian Insufficiency (POI) is a multi-factorial disorder that affects women of reproductive age. The condition is characterized by the loss of ovarian function before the age of 40 years and several factors have been identified to be implicated in its pathogenesis. Remarkably though, at least 50% of women have remaining follicles in their ovaries after the development of ovarian insufficiency. Population data show that approximately up to 3.7% of women worldwide suffer from POI and subsequent infertility. Currently, the treatment of POI-related infertility involves oocyte donation. However, many women with POI desire to conceive with their own ova. Therefore, experimental biological therapies, such as Platelet-Rich Plasma (PRP), Exosomes (exos) therapy, In vitro Activation (IVA), Stem Cell therapy, MicroRNAs and Mitochondrial Targeting Therapies are experimental treatment strategies that focus on activating oogenesis and folliculogenesis, by upregulating natural biochemical pathways (neofolliculogenesis) and improving ovarian microenvironment. This mini-review aims at identifying the main advantages of these approaches and exploring whether they can underpin existing assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a debilitating autoimmune disease with grave physical, emotional and socioeconomic consequences. Despite advances in targeted biologic and pharmacologic interventions that have recently come to market, many patients with RA continue to have inadequate response to therapies, or intolerable side effects, with resultant progression of their disease. In this review, we detail multiple biomolecular pathways involved in RA disease pathogenesis to elucidate and highlight pathways that have been therapeutic targets in managing this systemic autoimmune disease. Here we present an up-to-date accounting of both emerging and approved pharmacological treatments for RA, detailing their discovery, mechanisms of action, efficacy, and limitations. Finally, we turn to the emerging fields of bioengineering and cell therapy to illuminate possible future targeted therapeutic options that combine material and biological sciences for localized therapeutic action with the potential to greatly reduce side effects seen in systemically applied treatment modalities.

Premature Ovarian Insufficiency (POI) is a multi-factorial disorder that affects women of reproductive age. The condition is characterized by the loss of ovarian function before the age of 40 years and several factors have been identified to be implicated in its pathogenesis. Remarkably though, at least 50% of women have remaining follicles in their ovaries after the development of ovarian insufficiency. Population data show that approximately up to 3.7% of women worldwide suffer from POI and subsequent infertility. Currently, the treatment of POI-related infertility involves oocyte donation. However, many women with POI desire to conceive with their own ova. Therefore, experimental biological therapies, such as Platelet-Rich Plasma (PRP), Exosomes (exos) therapy, In vitro Activation (IVA), Stem Cell therapy, MicroRNAs and Mitochondrial Targeting Therapies are experimental treatment strategies that focus on activating oogenesis and folliculogenesis, by upregulating natural biochemical pathways (neo-folliculogenesis) and improving ovarian microenvironment. This mini-review aims at identifying the main advantages of these approaches and exploring whether they can underpin existing assisted reproductive technologies.

Asthma is a highly prevalent disease, one of the chronic diseases with the highest economic costs; thus, it imposes a high economic burden on society, the healthcare system, patients, and third-party payers. Contrary to this study, until now, systematic reviews of economic evaluations (EEs) of treatments for severe asthma have not been exclusively focused on biological treatments, and have included a small number of studies and only model-based EEs. This study systematically reviews EEs of biological therapies for severe asthma published until December 2022 using PRISMA guidelines. The review analyzes the cost-effectiveness of biologicals in comparison to SOC, or SOC plus OCS. The quality of the EEs is assessed using Consensus on Health Economics Checklist extended (CHEC-extended). Thirty-nine studies were eligible: 15 based on a Markov model, and 19 trial-based; eight adopting societal and NHS perspectives, and seven the payer's perspective. The reviewed EEs addressed cost-effectiveness, cost-utility, and incremental costs and outcomes comparison. Their findings were mainly expressed through ICER-incremental cost-effectiveness ratio (24 studies: 13 concluded that biological were cost-effective) and cost comparison analysis (14 studies: 6 concluded that biological were cost-effective), and were sensitive to a wide variety of factors (e.g. medication cost, treatment response, time horizon, utility benefits, mortality, exacerbation rate, discount rate, etc.) There has been some ambiguity concerning the EE of biological therapies due to variation in choice of study design and contradictory results. Nevertheless, it can be concluded that biological treatments improve health outcomes, in many contexts at a high cost. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the first cause of death worldwide, with a heavy social and economic impact. They include a wide range of pathological conditions, among which cardiac fibrosis represents a common pathogenetic hallmark. The fibrotic process is driven by cardiac mesenchymal stromal cells, namely fibroblasts, which become activated, proliferate, and differentiate into myofibroblasts in response to several stimuli, in the end secreting extracellular matrix proteins, and mediating cardiac tissue remodelling and stiffening. A specific therapy for the exclusive treatment of cardiac fibrosis is still lacking. Given the growing quest for reducing the burden of cardiovascular diseases, there is increasing interest in the search for new effective anti-fibrotic therapies. In this review, we will briefly summarize the limited pharmacological therapies known to act, at least in part, against cardiac fibrosis. Then we will present novel potential active molecules, molecular targets, and biotechnological approaches emerged in the last decade, as possible future therapeutic strategies for cardiac fibrosis, with a specific focus on targeting fibroblast activation and function. [ABSTRACT FROM AUTHOR]

Case report: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. Discussion: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases. [ABSTRACT FROM AUTHOR]

Objective: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. Methods: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. Results: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). Conclusions: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Psoriasis and vitiligo are two autoimmune, multi-factorial, chronic diseases with an increased prevalence worldwide. Although the clinical characteristics are different, multiple associations are observed between the two conditions. The literature describes numerous directions regarding management focused on either psoriasis or vitiligo, seen as two separate entities. For this reason, current studies related to this association are converging towards new horizons that allow the use of a single therapy, personalized and equally focused on both conditions. The aim of this paper is to formulate an overview of the current knowledge regarding psoriasis and vitiligo and to determine a possible relation between them. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic inflammatory disease manifesting as erythematous and desquamative dermatoses. This study estimated the cost per responder (CPR) for the treatment of moderate-to-severe plaque psoriasis with biologic therapies approved by the Colombian regulatory agency. This secondary study used a modeling based CPR estimation to evaluate psoriasis therapies in Colombia. We calculated CPR of achieving Psoriasis Area and Severity Index (PASI) scores of 75, 90, and 100 for biological treatments based on the number needed to treat (NNT), reported in previously published network meta-analyses. We calculated CPR for the first year and for the maintenance period. We ranked alternatives using the estimated CPR from each literature source using the Borda count method. Adalimumab, infliximab and etanercept were the least expensive alternatives. Ixekizumab, guselkumab and secukinumab were the treatments with the lowest NNT for PASI 75, 90, and 100. For both first year and maintenance periods, adalimumab, infliximab, guselkumab and ixekizumab had the lowest CPR. Sensitivity analyzes showed consistent results. The application of CPR analysis of biologics to treat plaque psoriasis demonstrated that adalimumab, infliximab, guselkumab, and ixekizumab had the lowest CPR in the first year of treatment and during the maintenance period. [ABSTRACT FROM AUTHOR]

Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/- mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis. Six drug trials have reported encouraging results, with an improvement in multiple clinical and serological outcome measures. The possibility of combining B-cell depletion and anti-BLyS treatment has also been successfully explored. [ABSTRACT FROM AUTHOR]

A triad of symptoms characterises Felty's syndrome: seropositive rheumatoid arthritis (RA), splenomegaly and neutropenia. The treatment of Felty's syndrome is based on using classic synthetic and biological disease-modifying anti-rheumatic drugs (DMARDs). In this article, we present a case of a patient with Felty's syndrome who was treated with biologic treatment. A systematic search of the literature on the electronic medical database was conducted. The drugs from the DMARD group, despite reducing the activity of the disease, may cause significant clinical complications. It is important to know about the diagnosis, differentiation and treatment of neutropenia and the prevention of febrile neutropenia. The article discusses the current therapeutic possibilities using both classical and biologic DMARDs. [ABSTRACT FROM AUTHOR]

(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79–9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine–acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine–acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Despite years of experience with biological disease modifying anti-rheumatic drugs (bDMARD) in rheumatoid arthritis (RA), little is known about differences in infectious risk among bDMARDs. The aim of this study was to assess the incidence and type of infections in RA patients on bDMARDs and to determine possible predictors. Methods: A retrospective multicenter cohort study that included patients registered in the Rheumatic Diseases Portuguese Registry (Reuma.pt) with RA, and exposed to at least one bDMARD until April 2021. RA patients under bDMARD and with at least one episode of severe infection (SI), defined as infection that requires hospitalization, use of parenteral antibiotics or that resulted in death, were compared to patients with no report of SI. Demographic and clinical data at baseline and at the time of each SI were collected to establish comparisons between different groups of bDMARDs. Comparisons between different bDMARDs were assessed and logistic regression was performed to identify predictors of SI. Results: We included 3394 patients, 2833 (83.5%) female, with a mean age at RA diagnosis of 45.5±13.7 years. SI was diagnosed in 142 of the 3394 patients evaluated (4.2%), totaling 151 episodes of SI. At baseline, patients with SI had a significantly higher proportion of prior orthopedic surgery, asthma, interstitial lung disease, chronic kidney disease and corticosteroid use, higher mean age and longer median disease duration at first bDMARD. Nine patients died (6.0%). Ninety-two SI (60.9%) occurred with the first bDMARD, the majority leading to discontinuation of the bDMARD within 6 months (n=75, 49.7%), while 65 (43.0%) restarted the same bDMARD and 11 (7.3%) switched to another bDMARD (6 of them to a different mechanism of action). In the multivariable analysis, we found that chronic kidney disease, asthma, infliximab, corticosteroid use, interstitial lung disease, previous orthopedic surgery, higher Health Assessment Questionnaire and DAS284V-ESR are independent predictors of SI. Conclusion: This study described the incidence and types of SI among Portuguese RA patients on biologics, identifying several predictors of SI, both globally and with different bDMARDs. Physicians should be aware of the real-word infectious risk in RA patients on bDMARDs when making treatment decisions. [ABSTRACT FROM AUTHOR]

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 109/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. Methodology: Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population‐based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. Results: There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non‐significant increase in risk of ALT flare among the HBV‐exposed group (27.6% vs. 23.7%, p =.055). In multivariable analysis, using prednisolone‐equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti‐CD20 when compared to other biological agents (36.1% vs. 14.5%, p <.01), but was not significantly different among anti‐tumour necrosis factor, anti‐cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti‐integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p =.82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti‐CD20. Conclusions: Our study further supports the current suggestion of prophylactic anti‐viral before starting anti‐CD20 in HBV‐exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) is the most frequently encountered autoimmune rheumatic disease in children. To our knowledge, this is the first study aimed to estimate the frequency of Toxoplasma gondii (T. gondii) and Toxocara seropositivity in JIA and assess its relation to the disease activity, IL-10 levels, and type of the received therapies. This study was conducted on 43 JIA patients and 50 cases as a control group. All participants were evaluated by disease activity score (JADAS-27), and the presence of specific IgG and IgM antibodies against T. gondii and IgG against Toxocara species using an enzyme-linked immunosorbent assay. IL-10 serum levels were measured using an ELISA kit. The results show that JIA patients have significantly higher seropositivity for anti-T. gondii IgG compared to control subjects (p = 0.02) and a non-significant difference for Toxocara seropositivity (p = 0.41). All participants were negative for IgM anti-Toxoplasma gondii. Demographic parameters did not significantly affect these seroprevalence frequencies (p > 0.05). IL-10 was significantly higher among JIA patients compared to controls (p = 0.007) and seropositive anti-T. gondii JIA exhibited significantly higher IL-10 levels compared to seronegative ones (p = 0.03). Seropositive anti-T. gondii IgG JIA patients had a significantly higher disease activity score (JADAS-27) than seronegative anti-T. gondii IgG cases (p = 0.02). There was a significant positive correlation between anti-T. gondii IgG and JADAS-27 score (p = 0.009). A significant association was detected between T. gondii infection and DMARDs including the biological therapies (p

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long-term efficacy of most approaches is poor. Cell-based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low-risk, low-cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell-based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren’s syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts’ input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Summary: Background: Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population. Methods: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236. Findings: The systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints. Interpretation: In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies. Funding: None.

Objectives PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial. Methods Adult patients with active PsA (n  = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment–PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo. Results At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P  < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P  < 0.01). Conclusion Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03675308 [ABSTRACT FROM AUTHOR]

Depression is an independent mood disorder and one of the most common comorbidities of rheumatoid arthritis (RA). Growing evidence suggests that there is two-way regulation between RA and depression, resulting in a vicious cycle of RA, depression, poor outcomes, and disease burden. The rising prevalence of RA-associated depression warrants a re-examination of the relationships between them. Here we provide an overview of the etiology and pathological mechanisms of RA-associated depression, and recent advances in treatment with biologics, which will facilitate the development of new and effective prevention and treatment strategies. [ABSTRACT FROM AUTHOR]