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Background: In contrast to previous network meta-analysis using classical frequentist methods, we evaluated the efficacy and safety of six frequently-used biologics through a Bayesian method. Methods: Web of Science, Scopus, CENTRAL, ClinicalTrials.gov and ICTRP were searched to collect randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn's disease, comparing Infliximab, Adalimumab, Certolizumab pegol, Ustekinumab, Risankizumab, or Vedolizumab, relative to placebo or an active comparator for induction of clinical response (two different definitions) and maintenance of clinical remission. A random-effects model was performed with rankings according to the surface under cumulative ranking curve (SUCRA) probability. Finally, we completed sensitivity and consistency analyses, and evaluated the certainty of evidence through GRADE working group guidance. Results: We identified 22 and 20 RCTs for induction and maintenance therapy, respectively. Infliximab combined with azathioprine was most effective for inducing clinical response in TNF (tumor necrosis factor) antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab (SUCRA 86.19) and Risankizumab (SUCRA 62.56) have the largest SUCRA in induction of clinical response. Risankizumab has the lowest risk of adverse events (SUCRA 84.81), serious adverse events (SUCRA 94.23), and serious infections (SUCRA 79.73) in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab rank highest for maintaining clinical remission. Conclusion: This analysis suggests that Infliximab in combination with azathioprine may be preferred biologic agents for induction therapy in TNF antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab and Risankizumab may be preferred biologic agents for induction therapy. Risankizumab potentially has the lowest safety risk worth exploring in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab have maintenance efficacy benefits for responders to induction therapy. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=458609, Identifier CRD42023458609. [ABSTRACT FROM AUTHOR]

Background: Autoimmune disorders have primary manifestations such as joint pain and bowel inflammation but can also have secondary manifestations such as non-infectious uveitis (NIU). A regulatory health authority raised concerns after receiving spontaneous reports for NIU following exposure to Remicade®, a biologic therapy with multiple indications for which alternative therapies are available. In assessment of this clinical question, we applied validity diagnostics to support observational data causal inferences. Methods: We assessed the risk of NIU among patients exposed to Remicade® compared to alternative biologics. Five databases, four study populations, and four analysis methodologies were used to estimate 80 potential treatment effects, with 20 pre-specified as primary. The study populations included inflammatory bowel conditions Crohn's disease or ulcerative colitis (IBD), ankylosing spondylitis (AS), psoriatic conditions plaque psoriasis or psoriatic arthritis (PsO/PsA), and rheumatoid arthritis (RA). We conducted four analysis strategies intended to address limitations of causal estimation using observational data and applied four diagnostics with pre-specified quantitative rules to evaluate threats to validity from observed and unobserved confounding. We also qualitatively assessed post-propensity score matching representativeness, and bias susceptibility from outcome misclassification. We fit Cox proportional-hazards models, conditioned on propensity score-matched sets, to estimate the on-treatment risk of NIU among Remicade® initiators versus alternatives. Estimates from analyses that passed four validity tests were assessed. Results: Of the 80 total analyses and the 20 analyses pre-specified as primary, 24% and 20% passed diagnostics, respectively. Among patients with IBD, we observed no evidence of increased risk for NIU relative to other similarly indicated biologics (pooled hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.38–1.40). For patients with RA, we observed no increased risk relative to similarly indicated biologics, although results were imprecise (HR: 1.23, 95% CI 0.14–10.47). Conclusions: We applied validity diagnostics on a heterogenous, observational setting to answer a specific research question. The results indicated that safety effect estimates from many analyses would be inappropriate to interpret as causal, given the data available and methods employed. Validity diagnostics should always be used to determine if the design and analysis are of sufficient quality to support causal inferences. The clinical implications of our findings on IBD suggests that, if an increased risk exists, it is unlikely to be greater than 40% given the 1.40 upper bound of the pooled HR confidence interval. [ABSTRACT FROM AUTHOR]

Background: Autoimmune disorders have primary manifestations such as joint pain and bowel inflammation but can also have secondary manifestations such as non-infectious uveitis (NIU). A regulatory health authority raised concerns after receiving spontaneous reports for NIU following exposure to Remicade®, a biologic therapy with multiple indications for which alternative therapies are available. In assessment of this clinical question, we applied validity diagnostics to support observational data causal inferences. Methods: We assessed the risk of NIU among patients exposed to Remicade® compared to alternative biologics. Five databases, four study populations, and four analysis methodologies were used to estimate 80 potential treatment effects, with 20 pre-specified as primary. The study populations included inflammatory bowel conditions Crohn's disease or ulcerative colitis (IBD), ankylosing spondylitis (AS), psoriatic conditions plaque psoriasis or psoriatic arthritis (PsO/PsA), and rheumatoid arthritis (RA). We conducted four analysis strategies intended to address limitations of causal estimation using observational data and applied four diagnostics with pre-specified quantitative rules to evaluate threats to validity from observed and unobserved confounding. We also qualitatively assessed post-propensity score matching representativeness, and bias susceptibility from outcome misclassification. We fit Cox proportional-hazards models, conditioned on propensity score-matched sets, to estimate the on-treatment risk of NIU among Remicade® initiators versus alternatives. Estimates from analyses that passed four validity tests were assessed. Results: Of the 80 total analyses and the 20 analyses pre-specified as primary, 24% and 20% passed diagnostics, respectively. Among patients with IBD, we observed no evidence of increased risk for NIU relative to other similarly indicated biologics (pooled hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.38–1.40). For patients with RA, we observed no increased risk relative to similarly indicated biologics, although results were imprecise (HR: 1.23, 95% CI 0.14–10.47). Conclusions: We applied validity diagnostics on a heterogenous, observational setting to answer a specific research question. The results indicated that safety effect estimates from many analyses would be inappropriate to interpret as causal, given the data available and methods employed. Validity diagnostics should always be used to determine if the design and analysis are of sufficient quality to support causal inferences. The clinical implications of our findings on IBD suggests that, if an increased risk exists, it is unlikely to be greater than 40% given the 1.40 upper bound of the pooled HR confidence interval. [ABSTRACT FROM AUTHOR]

To compare the effectiveness of retreatment of rheumatoid arthritis (RA) patients with rituximab (RTX) following the treat-to-target retreatment (TTr) or fixed interval retreatment (FIr) strategy. RA patients starting RTX treatment between January 2008 and June 2016, and receiving at least three infusion cycles were grouped by strategy (TTr, FIr or both). Primary outcome (between strategy difference in DAS28-CRP (Disease Activity Score in 28 joints calculated with C-reactive protein)) and secondary outcomes (flares, use of co-medication and mean yearly dose of RTX) were analyzed by group using linear mixed models to account for different strategies within patients. A total of 213 patients, 59 TTr (of whom 32 switched from TTr to FIr) and 186 FIr were included. No between-group difference in mean DAS28-CRP was found (0.10 DAS28-CRP point (95% CI − 0.07 to 0.26)). The TTr strategy did not result in more flares (IRR 1.13, 95%CI 0.87 to 1.47), conventional synthetic disease-modifying antirheumatic drug use (difference − 11.7%, 95%CI − 26.3% to 2.9%), or lower mean yearly RTX dose (difference 172 mg/yr, 95%CI − 355 to 11.7 mg/yr). RTX retreatment with either a TTr or FIr strategy does not seem to lead to better disease control and/or less drug use when used in a DAS28-CRP treat-to-target context. Choice of either strategy can, therefore, be made based on patient and physician preferences and logistical context. [ABSTRACT FROM AUTHOR]

Introduction: Behçet's syndrome (BS) is a chronic multisystem disease that mainly occurs along the ancient Silk Road. Uveitis is a major manifestation of BS with potentially a high visual morbidity. Early diagnosis of BS uveitis (BSU) based on characteristic ocular findings can be helpful in appropriate management of the patients. Areas covered: A comprehensive literature review was conducted in PubMed database. New advances in the diagnosis and management of BSU were reviewed. Expert opinion: The diagnosis of BSU is based on a combination of clinical findings. New sets of diagnostic/classification criteria have been developed including the International Criteria for Behçet Disease and the Standardization of Uveitis Nomenclature (SUN) working group criteria. An algorithm for the diagnosis of BSU based on characteristic ocular findings has been recently proposed to help ophthalmologists in predicting BS diagnosis in patients presenting with isolated uveitis. Treatment of BSU is currently based on the European Alliance of Associations for Rheumatology (EULAR) and the French recommendations. Treatment of anterior uveitis is based on topical corticosteroids with mydriatics unless there are high risk factors for poor visual outcomes. Posterior segment involvement requires the combination of systemic corticosteroids, and immunosuppressive or immunomodulating agents. Anti TNFα or IFN-α2a should be considered in non-responsive patients or in those with acute severe inflammatory attack. [ABSTRACT FROM AUTHOR]

Background/Objectives: Polymyalgia Rheumatica (PMR) is an inflammatory condition that primarily affects individuals aged 50 and older, especially in Western countries. Although glucocorticoids are the cornerstone of PMR treatment, these drugs are associated with side effects, making it advisable to use them for the shortest duration possible. However, tapering or discontinuation of glucocorticoids often leads to disease relapses. In this review, we focus on the traditional management of PMR, as well as the potential for therapies that may reduce glucocorticoid use. Special attention is given to the efficacy of biologic agents in PMR management. Methods: A literature review, primarily based on articles published in PubMed, was conducted. In addition to discussing various glucocorticoids and conventional disease-modifying drugs used for the management of isolated PMR, this review specifically focused on the information reported regarding new therapies, with particular emphasis on biologic agents. Results: Prednisone or prednisolone at a dose ranging between 12.5 and 25 mg/day is the agreed-upon treatment for PMR. Due to the side effects associated with prolonged glucocorticoid use and the high frequency of relapses when glucocorticoids are tapered, glucocorticoid-sparing agents have emerged as tools in the management of PMR. Methotrexate has traditionally been the conventional disease-modifying antirheumatic drug (DMARD) unanimously recommended for use in PMR. Other conventional DMARDs, such as leflunomide, have shown promising results but require further study. The use of biologic agents has marked a significant step forward in the management of PMR. While anti-TNF agents failed to provide beneficial effects in isolated PMR, anti-IL-6 receptor agents, such as tocilizumab and sarilumab, have demonstrated efficacy in reducing relapse frequency, lowering the cumulative glucocorticoid burden, and achieving long-term remission of the disease. Other biologic agents, many of which have been used in giant cell arteritis, as well as Janus kinase (JAK) inhibitors, are currently under investigation. Conclusions: Glucocorticoids are the primary treatment for isolated PMR but are associated with comorbidities, especially in patients with pre-existing conditions or frequent relapses. Glucocorticoid-sparing agents, such as methotrexate and biologics, in particular tocilizumab and sarilumab, offer alternatives, improving symptoms and reducing glucocorticoid use. While biologic agents reduce long-term side effects and help achieve disease remission, their use must consider potential side effects and higher costs compared to traditional therapies. [ABSTRACT FROM AUTHOR]

Children and adolescents suffering from moderate‐to‐severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p‐value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08–8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71–10.02), EASI 50 (OR 8.89; 95% CI 6.18–12.78) and EASI 90 (8.30; 95% CI 4.81–14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34–9.90) or 4 points or more (OR 8.09; 95% CI 5.19–12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58–1.07), and conjunctivitis (OR 2.08; 95% CI 1.00–4.33). In this meta‐analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population. [ABSTRACT FROM AUTHOR]

Managing psoriasis (PsO) and its comorbidities, particularly psoriatic arthritis, often involves using interleukin (IL)-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. This study evaluates the risk of developing psoriatic arthritis in patients treated with IL-23 inhibitors compared to IL-12/23 inhibitors. This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with PsO. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of psoriatic arthritis (PsA), analyzed using a Cox regression hazard model and Kaplan-Meier estimates. The study included matched cohorts of patients treated with IL-23 inhibitors (n = 2273) and IL-12/23 inhibitors (n = 2995). Cox regression analysis revealed no significant difference in the cumulative incidence of PsA between the IL-23i and IL-12/23i cohorts (P =.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic PsO in both cohorts over the study period. Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. No significant difference but a numerically lower risk of psoriatic arthritis in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors was found, underscoring their comparable efficacy in PsO management and follow-up. [ABSTRACT FROM AUTHOR]

Elderly-onset rheumatoid arthritis (EORA) is a distinct subtype of rheumatoid arthritis characterized by heightened treatment challenges due to immune aging and the complexity of comorbidities. This review systematically summarizes the definition, clinical features, epidemiological trends, therapeutic challenges, and the potential applications of biologic agents in EORA. It primarily focuses on the efficacy, safety, and individualized treatment strategies associated with various biologic agents. Studies indicate that biologics, such as TNF-α inhibitors, IL-6 inhibitors, and JAK inhibitors, can significantly reduce inflammation and improve joint function in EORA patients. However, their long-term use is closely linked to increased risks of infections, thrombosis, and malignancies, underscoring the importance of personalized treatment approaches and dynamic monitoring. Moreover, the advent of novel biologic agents, including IL-17 and IL-23 inhibitors, as well as second-generation JAK inhibitors, offers additional therapeutic options for refractory patients and demonstrates substantial potential in optimizing both efficacy and safety. With the rapid progress of precision medicine and artificial intelligence (AI) technologies, gene profiling, biomarker analysis, and AI-assisted decision-making are gradually steering EORA treatment towards more personalized and precise strategies. However, the high cost of treatment and the limited accessibility of these technologies remain significant barriers in clinical practice. Future research should focus on validating the long-term safety of novel therapies and refining individualized treatment strategies to enhance patient outcomes and quality of life.

BackgroundIn contrast to previous network meta-analysis using classical frequentist methods, we evaluated the efficacy and safety of six frequently-used biologics through a Bayesian method.MethodsWeb of Science, Scopus, CENTRAL, ClinicalTrials.gov and ICTRP were searched to collect randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn’s disease, comparing Infliximab, Adalimumab, Certolizumab pegol, Ustekinumab, Risankizumab, or Vedolizumab, relative to placebo or an active comparator for induction of clinical response (two different definitions) and maintenance of clinical remission. A random-effects model was performed with rankings according to the surface under cumulative ranking curve (SUCRA) probability. Finally, we completed sensitivity and consistency analyses, and evaluated the certainty of evidence through GRADE working group guidance.ResultsWe identified 22 and 20 RCTs for induction and maintenance therapy, respectively. Infliximab combined with azathioprine was most effective for inducing clinical response in TNF (tumor necrosis factor) antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab (SUCRA 86.19) and Risankizumab (SUCRA 62.56) have the largest SUCRA in induction of clinical response. Risankizumab has the lowest risk of adverse events (SUCRA 84.81), serious adverse events (SUCRA 94.23), and serious infections (SUCRA 79.73) in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab rank highest for maintaining clinical remission.ConclusionThis analysis suggests that Infliximab in combination with azathioprine may be preferred biologic agents for induction therapy in TNF antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab and Risankizumab may be preferred biologic agents for induction therapy. Risankizumab potentially has the lowest safety risk worth exploring in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab have maintenance efficacy benefits for responders to induction therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=458609, Identifier CRD42023458609.

Machine learning (ML) has been applied to predict the efficacy of biologic agents in ulcerative colitis (UC). ML can offer precision, personalization, efficiency, and automation. Moreover, it can improve decision support in predicting clinical outcomes. However, it faces challenges related to data quality and quantity, overfitting, generalization, and interpretability. This paper comments on two recent ML models that predict the efficacy of vedolizumab and ustekinumab in UC. Models that consider multiple pathways, multiple ethnicities, and combinations of real-world and clinical trial data are required for optimal shared decision-making and precision medicine. This paper also highlights the potential of combining ML with computational models to enhance clinical outcomes and personalized healthcare. Key Insights: (1) ML offers precision, personalization, efficiency, and decision support for predicting the efficacy of biologic agents in UC. (2) Challenging aspects in ML prediction include data quality, overfitting, and interpretability. (3) Multiple pathways, multiple ethnicities, and combinations of real-world and clinical trial data should be considered in predictive models for optimal decision-making. (4) Combining ML with computational models may improve clinical outcomes and personalized healthcare. [ABSTRACT FROM AUTHOR]

Introduction: The advent of disease‐modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings. Methods: To contextualize such issues, the present study compared anti‐amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis. Results: The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states. Discussion: These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti‐amyloid biologic agents for the prevention of cognitive loss. While the era of disease‐modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD. Highlights: Anti‐amyloid therapy costs are comparable to other commonly used biologics.Anti‐amyloid therapy efficacy is comparable to other commonly used biologics.Anti‐amyloid therapy safety is compatible with other commonly used biologics. [ABSTRACT FROM AUTHOR]

IntroductionPlaque psoriasis is a persistent skin disorder that necessitates efficient management. This study investigates the therapeutic effectiveness and timeline for skin lesion resolution in plaque psoriasis patients treated with combined biologic agents compared to standard therapies.MethodsConducted retrospectively between March 2020 and March 2023, the study included 162 patients with moderate to severe plaque psoriasis. Participants were divided into two groups: the Control Group, which received standard treatments, and the Combined Biologic Agent Group, which received additional biologic therapy with secukinumab. Participants in the Control Group received standard treatments, while those in the Combined Biologic Agent Group received standard treatments plus secukinumab.ResultsThe results showed that the Combined Biologic Agent Group experienced a significantly faster onset of therapeutic effects, with an average time of 3.04 ± 2.25 days compared to 6.12 ± 2.06 days in the Control Group. Additionally, skin lesion resolution occurred more rapidly in the biologic agent group (7.04 ± 2.13 days) than in the control group (14.56 ± 4.73 days). By week 24, the Psoriasis Area and Severity Index (PASI) scores demonstrated a more substantial reduction in the biologic agent group, decreasing from 26.98 ± 11.28 to 2.48 ± 3.01, whereas the control group showed a reduction from 25.82 ± 10.47 to 10.40 ± 7.63. The overall effectiveness rate was higher in the biologic agent group, with no cases of ineffectiveness, compared to a 20.99% ineffectiveness rate in the control group. Furthermore, there was no recurrence of the disease in the biologic agent group, while the control group experienced an 11.11% recurrence rate. Both groups had a similar incidence of adverse reactions, indicating that the addition of biologic agents does not significantly increase the risk of adverse events.DiscussionThese findings suggest that combined biologic agent therapy offers a more effective and faster treatment option for plaque psoriasis without compromising safety. However, larger-scale clinical trials are necessary to validate these results and establish the long-term benefits and safety of this treatment approach in diverse patient populations.

Systemic sclerosis (SSc), as an immune-mediated chronic connective tissue disease, is mainly characterized by fibrosis of multiple organs, including the skin and lungs. It is a rare disease, with a high incidence and mortality among rheumatic immune diseases. At present, there is no effective drug for the treatment of SSC. In recent years, it has been found that the interactions between T/B lymphocytes, fibroblasts, endothelial cells, and various pro-inflammatory and fibrotic signaling molecules play a crucial role in the occurrence and development of SSc. On this basis, a series of targeted drugs are currently being tested. CD20 monoclonal antibodies (Rituximab), IL-6 receptor antagonists (Tocilizumab), and multi-target tyrosine kinase inhibitors (Nintedanib) have been approved for the treatment of SSc or SSc-ILD by FDA. In addition, other targeted drugs such as Janus kinase inhibitors and various interleukin inhibitors have shown preliminary therapeutic potentials through clinical trials. This article reviews the research progress in targeted therapies for SSc by synthesizing the latest evidence from four aspects: targeting B lymphocytes, T lymphocytes, vascular endothelial cells, and pro-inflammatory and fibrotic signaling molecules.

Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride:urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: Tocilizumab may be the most efficient remission-inducing and relapse-lowering biological agent for patients with GCA, and TNF inhibitors pose the highest risk of infection among the biologics studied.

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this group, and no studies have examined the vaccination status of patients’ close contacts. Objectives: To assess vaccination rates among patients on biologics and their household contacts, identifying reasons for inadequate vaccination and examining factors influencing vaccination status and attitudes is crucial. Methods: A cross-sectional study was conducted from September 2022 to February 2023 at the two hospitals in Heraklion, Crete, including adult and pediatric patients on biologics. Data were collected through medical records and interviews and analyzed using Microsoft Excel 2016 and MedCalc2006. Results: Among the 446 adults, vaccination rates were as follows: 83% for COVID-19, 73.8% for influenza, 64.5% for the pneumococcal conjugate vaccine, 29.6% for the pneumococcal polysaccharide vaccine, and 4% for Tdap. Among the 26 children included, those with basic immunization schedule coverage exceeded 96%, but rates for the vaccines usually administered at adolescence were lower (Tdap: 47.8%, HPV: 42.1%, MenACWY: 66.7%). COVID-19 vaccination was at 38.5%. Regarding the additional vaccines recommended due to treatment-induced immunosuppression, 69.2% of pediatric patients received the annual influenza vaccine, while only 19.2% received the pneumococcal polysaccharide vaccine. Household contacts demonstrated low vaccination rates (p < 0.007) and older age (by 1 year, p < 0.001) were associated with favorable attitudes and higher coverage in adults, while in pediatric patients, no statistically significant associations were found. A lack of physician recommendation was the primary reported reason for not being vaccinated. Conclusions: Significant vaccination gaps exist among patients on biologics and their close contacts, largely due to inadequate physician recommendations. Raising awareness and strengthening healthcare provider roles are essential to improve coverage in this high-risk group.

Background: Corticosteroids are recommended only for induction of remission in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to evaluate the change in pharmacologic treatment use, particularly systemic corticosteroids, over approximately 30 years, and the impact of biologics on IBD treatment since their appearance in the 2000s. Methods: This retrospective study conducted in Japan used data from the Phoenix cohort database (January 1990 to March 2021). Patients with disease onset at age ≥ 10 years who received treatment for UC or CD between January 1990 and March 2021 were included. Outcome measures were change in IBD treatments used, total cumulative corticosteroid doses, initial corticosteroid dose, duration of corticosteroid treatment, and surgery rate. Results: A total of 1066 and 579 patients with UC and CD, respectively, were included. In UC, the rate of corticosteroid use as initial treatment was relatively stable regardless of the year of disease onset; however, in CD, its rate decreased in patients who had disease onset after 2006 (before 2006: 14.3–27.8% vs. after 2006: 6.6–10.5%). Compared with patients with disease onset before biologics became available, cumulative corticosteroid doses in both UC and CD, and the surgery rate in CD only, were lower in those with disease onset after biologics became available. Conclusions: Since biologics became available, corticosteroid use appears to have decreased, with more appropriate use. Furthermore, use of biologics may reduce surgery rates, particularly in patients with CD. UMIN Clinical Trials Registry; UMIN000035384. [ABSTRACT FROM AUTHOR]

Background: The risk of developing non-melanoma skin cancers (NMSCs) in patients with psoriasis is highly debated, and, to date, there is no unambiguous consensus opinion. Psoriasis is known to be related to an increased likelihood of other comorbidities such as psoriatic arthritis, obesity, metabolic syndrome, depression, and cardiovascular disease. Regarding cancer risk, previous studies have reported a greater tendency for the development of cutaneous T-lymphomas and colon, breast, kidney, and lung cancers. Furthermore, data from network meta-analyses have shown that patients with psoriasis have a higher risk of developing squamous cell carcinomas (SCCs) and/or basal cell carcinomas (BCCs). Multiple factors may contribute to the development of NMSCs in psoriatic patients, ranging from immunosuppression induced by biologic agents to previous phototherapy. However, the extent to which each factor may impact this risk has not been entirely assessed. The aim of this study was to evaluate the risk of developing NMSCs in patients with psoriasis observed for at least 5 years, by directly comparing patients only treated with phototherapy and patients treated with anti-tumor necrosis factor α (TNFα) agents, naive to other systemic treatments or phototherapy. Methods: We conducted a single-center retrospective study at Siena University Hospital, Italy, on 200 adult patients with psoriasis divided into two groups: (i) group 1, including 100 patients treated with narrow-band UVB phototherapy (nb-UVB), and (ii) group 2, including 100 patients treated with anti-TNFα. The patients included in group 2 had to be naive to cDMARDs and biologics and treated with anti-TNFα continuously for 5 years without loss of efficacy. All patients were observed for 5 years and underwent annual dermatologic examinations to assess for the occurrence of BCC or SCC. Results: A total of 34 out of 100 patients treated with phototherapy had one BCC or one SCC and 10 out of 34 developed two skin cancers. In particular, five had both types (one BCC and one SCC), and five had two BCCs. Conclusions: The results of our study highlight how the risk of developing NMSCs is greater in patients undergoing phototherapy compared to those treated with anti-TNFα. It also draws attention to the consideration that patients with scalp psoriasis might need closer follow-up as they could be more at risk of developing NMSCs. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc), as an immune-mediated chronic connective tissue disease, is mainly characterized by fibrosis of multiple organs, including the skin and lungs. It is a rare disease, with a high incidence and mortality among rheumatic immune diseases. At present, there is no effective drug for the treatment of SSC. In recent years, it has been found that the interactions between T/B lymphocytes, fibroblasts, endothelial cells, and various pro-inffammatory and fibrotic signaling molecules play a crucial role in the occurrence and development of SSc. On this basis, a series of targeted drugs are currently being tested. CD20 monoclonal antibodies ( Rit- uximab), IL-6 receptor antagonists (Tocilizumab), and multi-target tyrosine kinase inhibitors ( Nintedanib) have been approved for the treatment of SSc or SSc-ILD by FDA. In addition, other targeted drugs such as Janus kinase inhibitors and various interleukin inhibitors have shown preliminary therapeutic potentials through clinical trials. This article reviews the research progress in targeted therapies for SSc by synthesizing the latest evidence from four aspects: targeting B lymphocytes, T lymphocytes, vascular endothelial cells, and pro-inffammatory and fibrotic signaling molecules. [ABSTRACT FROM AUTHOR]

This article presents a post hoc analysis of the RELight study, which investigated the clinical benefit of switching from omalizumab to mepolizumab in patients with severe asthma. The study found that patients who switched to mepolizumab experienced a reduction in asthma exacerbations, improved asthma control, and a decrease in oral corticosteroid intake. These improvements were observed regardless of whether the patients had previously received omalizumab treatment. The findings suggest that switching therapies may be beneficial for patients with severe asthma who do not achieve optimal disease control. [Extracted from the article]

Biologic agents are increasingly being used to treat adult patients with systemic lupus erythematosus (SLE). However, the available data on biologic agents' use in childhood-onset SLE (cSLE) remains limited. To collate available evidence related to the efficacy and safety of using biologic agents in cSLE. The study followed the PRISMA checklist for reporting the data and conducted a thorough search using PubMed, Cochrane Library, and Scopus from January 2005 to August 2023. Only articles meeting specific criteria were included, focusing on cSLE, the use of biologic agents, and having outcome measures at six- and 12-month follow-ups for safety and efficacy. Case reports were excluded, and four independent reviewers screened the articles for accuracy, with a fifth reviewer resolving any discrepancies that arose to achieve a consensus. The final selection included 18 studies with a total of 593 patients treated with biologic agents for severe and/ or refractory cSLE. The most common indication for using biologic agents was lupus nephritis. Rituximab was used in 12 studies, while belimumab was used in six studies. The studies evaluated the efficacy of biologic agents based on SLE disease activity scores, laboratory parameter improvements, and reduced corticosteroid dosage. Positive outcomes were reported, with improvements in renal, hematologic, and immunologic parameters along with mild adverse effects, mostly related to mild infections and infusion reactions. Belimumab and rituximab have shown promise as potential treatments for severe and refractory cSLE cases, leading to decreased disease activity and complete or partial remission in many patients with an acceptable safety profile. However, further research is needed to better understand their benefits and potential risks in these patients. Key Points • This review emphasizes the lack of sufficient randomized controlled trials exploring the use of biologics in childhood systemic lupus erythematosus (cSLE). • Treatment plans for cSLE are being derived from those used for adult systemic lupus erythematosus. • According to current evidence, belimumab and rituximab can be potential treatment options for refractory and severe cases of cSLE. • Additional studies are required to reach more definitive conclusions. [ABSTRACT FROM AUTHOR]

Abstract Introduction The advent of disease‐modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings. Methods To contextualize such issues, the present study compared anti‐amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis. Results The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states. Discussion These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti‐amyloid biologic agents for the prevention of cognitive loss. While the era of disease‐modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD. Highlights Anti‐amyloid therapy costs are comparable to other commonly used biologics. Anti‐amyloid therapy efficacy is comparable to other commonly used biologics. Anti‐amyloid therapy safety is compatible with other commonly used biologics.

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Objective: To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. Methods: Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. Result: A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12 ± 14.70 (17 ∼ 85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self‐evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF‐ α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non‐affordable price. Conclusions: In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). Methods: Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. Results: At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. Conclusions: We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies. [ABSTRACT FROM AUTHOR]

Objective To investigate the 12-month renal remission in patients with lupus nephritis (LN) and the predictive factors. Methods The remission of patients with LN using biologic agents was analyzed by a prospective cohort study that included 57 patients with LN and positive urine protein, who were divided into hormone + immunosuppression group (n=39) and hormone + immunosuppression + biologics group (n=18) . Patients in hormone + immunosuppression group received standard therapy and those in hormone + immunosuppression + biologics group received standard therapy and belimumab. Long-term follow-up was assigned to collect and analyze data on renal response and clinical characteristics. Results Renal complete remission was achieved in 41 out of 57 patients (71.93%) and partial remission was achieved in 16 patients (28.07%) . Complete remission was achieved in 29 out of 39 patients in the hormone + immunosuppression group (mean time to complete remission was 7.846 months, 95%CI: 6.626-9.066 months) and in 12 out of 18 patients in the hormone + immunosuppression + biologics group (mean time to complete remission was 4.167 months, 95%CI: 3.461-4.872 months) .Conclusion Patients using both hormones, immune agents and biologics achieve complete remission more quickly than those using only hormones and immune agents. [ABSTRACT FROM AUTHOR]

Objective: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. Data source: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: ([“tuberculosis”] AND ([“children”] OR [“adolescent”]) AND [“rheumatic diseases”] AND ([“tumor necrosis factor-alpha”] OR [“etanercept”] OR [“adalimumab”] OR [“infliximab”] OR [“biological drugs”] OR [“rituximab”] OR [“belimumab”] OR [“tocilizumab”] OR [“canakinumab”] OR [“golimumab”] OR [“secukinumab”] OR [“ustekinumab”] OR [“tofacitinib”] OR [“baricitinib”] OR [“anakinra”] OR [“rilonacept”] OR [“abatacept”]), between January 2010 and October 2021. Data synthesis: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. Conclusions: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). Methods The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case–control study nestled within the cohort were identified. Results In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1–132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P  = 0.033, OR = 0.15; P  = 0.012, OR = 0.15; and P  = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P  = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). Conclusion Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable. [ABSTRACT FROM AUTHOR]

Two fundamental pathologic processes are central to the spectrum of chronic inflammation mechanisms: autoimmunity and autoinflammation. Autoimmunity and autoinflammation are mutually potent pathologic processes; their development is considered within the framework of the “immunoinflammatory” continuum, reflecting the close relationship between innate and acquired types of immune response. Autoimmunity is the leading mechanism of pathogenesis of a large group of chronic inflammatory human diseases, defined as autoimmune diseases, the frequency of which in the population exceeds 10%. Advances in molecular biology, pharmacogenetics and bioinformatics have created prerequisites for individualization of therapy of autoimmune rheumatic diseases within the concept of personalized medicine. The study of immunopathogenesis mechanisms, improvement of diagnostics, deciphering the nature of molecular taxonomy, development of approaches to prevention and personalized therapy of human autoimmune diseases is among the priority directions of medicine of the 21st century.

Objectives: Despite extensive research, there is currently no specific biomarker that reliably and universally indicates treatment response in psoriasis. Multiple studies have evaluated systemic inflammation markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic immune response index (SIRI) in psoriasis patients. However, there are limited studies investigating changes in these markers with biologic therapy. The goal of this study was to investigate the impact of biologic therapy on parameters including NLR, PLR, MLR, SII, and SIRI in patients with psoriasis. Methods: In this cohort study, we retrospectively evaluated 108 psoriasis patients who were on biological treatment, including interleukin (IL)17, IL23, and IL12/23 inhibitors, for a minimum of 12 weeks. We analyzed Psoriasis Area Severity Index (PASI) scores, complete blood count parameters, and C-reactive protein (CRP) levels both before and after 12 weeks of treatment. Results: The NLR, PLR, MLR, SII, SIRI, and CRP values all demonstrated a significant decrease, regardless of the specific type of biologic agent (p=0.001, 0.007, 0.011, <0.001, <0.001 and <0.001, respectively). Furthermore, we observed a statistically significant but low correlation between the reduction in PASI scores and PLR, SII, and SIRI values (p=0.036, r=0.202; p=0.042, r=0.196; p=0.023, r=0.219, respectively). Conclusion: The NLR, MLR, especially PLR, SII, and SIRI might be used as simple, convenient, and inexpensive laboratory markers to monitor the degree of inflammation and response to treatment after biologic therapy in daily practice. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common, chronic, inflammatory skin disorder affecting almost 2-3% of the population. Studies on the epidemiological data and the course of the disease have generally been published in pediatric and middle-aged patients, where the disease is more common. This study aimed to provide more insight into the disease and treatment characteristics of psoriasis patients over 65. Materials and Methods: In this retrospective, cross-sectional, single-center, hospital-based study, patients over 65 who visited our department between 01.06.2017 and 01.06.2020 were included. Results: Ninety six patients with psoriasis were admitted to our outpatient clinic during the study period. The mean age of the patients was 69.92±4.73 years. Women and men were equally affected. Almost 9.4% of the patients had psoriatic arthritis. The patients’ mean Psoriasis Area Severity Index score was 8.39±7.11, and the disease duration was 13.76±12.71 years. Nail involvement was detected in 43.8% of the patients. Family history was positive in 19.8% of the patients. Smoking was positive in 28.1% of the patients, and regular alcohol use was positive in 6.3%. Conclusion: The clinical course of psoriasis is usually milder in elderly onset patients. Further studies are warranted to determine the best management of psoriasis in elderly patients. Drug interactions and metabolism should be carefully managed in these patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies. Recent Findings: Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700–800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. Summary: The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a systemic disease encompassing autoimmunity, vasculopathy, and fibrosis. SSc is still burdened by high mortality and morbidity rates. Recent advances in understanding the pathogenesis of SSc have identified novel potential therapeutic targets. Several clinical trials have been subsequently designed to evaluate the efficacy of a number of new drugs. The aim of this review is to provide clinicians with useful information about these novel molecules. In this narrative review, we summarize the available evidence regarding the most promising targeted therapies currently under investigation for the treatment of SSc. These medications include kinase inhibitors, B-cell depleting agents, and interleukin inhibitors. Over the next five years, several new, targeted drugs will be introduced in clinical practice for the treatment of SSc. Such pharmacological agents will expand the existing pharmacopoeia and enable a more personalized and effective approach to patients with SSc. Thus, it will not only possible to target a specific disease domain, but also different stages of the disease. [ABSTRACT FROM AUTHOR]

Abstract Introduction Patients with psoriasis are at risk of depression, anxiety and adjustment disorder (DAAD). Randomized control trials reported improvement in depression and anxiety symptoms among patients with psoriasis receiving tumour necrosis factor inhibitors and ustekinumab (TNFi/UST) versus placebo and conventional systemic agents (CSA). The risk of DAAD among TNFi/UST versus CSA users was not assessed in real‐world settings. Objective To compare DAAD incidence among patients with psoriasis using CSA and subsequently received (vs. not) TNFi/UST. Methods We conducted a retrospective cohort study using the province of Quebec health administrative databases (1997–2015). Among adult patients with a diagnosis of psoriasis and initiating a CSA, we included those who later initiated a TNFi/UST, as a switch or add‐on, at the date of their first prescription fill (index‐date). We also included TNFi/UST nonusers at a date chosen to match the time between the first CSA and the index date of a random TNFi/UST user. TNFi/UST nonusers were classified into current or previous CSA users according to their last CSA received in the 90 days before or after their index date. Marginal structural Cox regression models weighted by the inverse probability of exposure compared the risk of DAAD between TNFi/UST, current and previous CSA users. Additional analyses were conducted by age group and sex. Results Our cohort included 1333 patients with psoriasis: 183 TNFi/UST users, 625 current CSA users and 525 previous CSA users. TNFi/UST users were at a lower risk of DAAD versus previous CSA users (hazard ratio 0.48, 95% confidence intervals: 0.28–0.94). The reduction in risk among TNFi/UST users was not statistically significant versus current CSA users. Similar results were observed across different age groups and sex. Conclusion Among patients with psoriasis receiving CSA, those who were subsequently dispensed TNFi/UST were at a lower risk of DAAD compared to those who did not receive these agents.

Abstract Background The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. Result There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. Conclusion This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.

Abstract Generalized pustular psoriasis (GPP) is a rare, chronic, and severe inflammatory skin disorder characterized by sudden eruption of sterile pustules, often accompanied by systemic inflammation. GPP flares can be life-threatening if untreated, owing to potential serious complications such as sepsis and cardiovascular failure. Diagnosis and clinical measurement of disease severity in GPP are often difficult. Lack of standardized criteria in the international guidelines and the heterogeneity of cutaneous and extracutaneous symptoms make the diagnosis of GPP difficult. Clinical criteria for description and diagnosis of pustular conditions, including GPP, are variable and there is no specific agreement on commonly sustained concepts. Differentiation of GPP from other similar conditions/diseases is important and requires careful assessments. The evidence that supports current topical or systemic therapies is largely based on case reports and small studies. Some biologic agents that target key cytokines involved in the activation of inflammatory pathways have been used as treatments for GPP. Recently, spesolimab, an IL-36R antagonist, has been approved in the USA and Japan for the treatment of GPP flares in adults, but there are no currently approved treatments for GPP in Europe. The IL-36 pathway has recently emerged as a central axis driving the pathogenic inflammatory mechanisms of GPP. Biologic agents that inhibit the IL-36 pathway have shown efficacy and safety in patients with GPP, addressing a generally considered unmet medical need.

Background and Aims: Anti-tumor necrosis factor agents (anti-TNFs) have become one of the primary medical therapies for Crohn’s disease (CD). We analyzed perceptions of infliximab and adalimumab in a large online community to better understand the information patients receive. Methods: Reddit, a vast online community, has several inflammatory bowel disease communities, the largest being /r/CrohnsDisease (rCD), with over 41,000 members. To better understand patient perceptions of biologics, we searched rCD for posts related to “infliximab,” “adalimumab,” and their relevant trade names. The top 20 yearly posts were extracted from 2011 to 2015 and 2011 to 2017, respectively. Manifest coding was performed. Codes were reassessed every 20 posts, resulting in 6 main sentiments. Total codes and per-comment codes were calculated for each sentiment. Percentages for each category were calculated by dividing by the total number of coded sentiments that year. Trends in rates of each sentiment were assessed using Spearman’s correlation coefficients. Results: 4486 comments were analyzed, and 4684 sentiments met our criteria. Negative sentiments decreased for both anti-TNFs over time (infliximab: rho = −0.90, P = .04, adalimumab: rho = −0.79, P = .04). In our primary analysis, adalimumab injection-related posts increased from 2012 to 2017 (rho = 0.83, P = .04). Positive sentiments and sentiments regarding drug costs, loss of efficacy, and diet remained stable. For infliximab and adalimumab, comment volume increased significantly over time (rho 0.90; P = .04, rho 0.89, P = .01). Conclusion: Our analysis of a large online community suggests a growing acceptance of biologic therapies among patients with CD over time. These data provide additional insight into the multifaceted framework shaping patients’ perceptions of anti-TNFs.

Psoriasis is a debilitating inflammatory condition that affects physiological and psychological states of millions around the world. Conventional biologic and nonbiologic therapies are fraught with profound adverse side effect profiles, frequent injection requirements, suboptimal outcomes, and other detriments. An enhanced understanding of the role of cytokines in psoriasis, particularly interleukins 12, 17, and 23, has afforded improved therapeutic strategies. Herein, we described the role of cytokines in psoriasis as well as current and prospective therapeutic approaches to treat this debilitating disease.

Chronic Urticaria (CU) is a skin disorder characterized by wheal and flare with a duration of more than 6 weeks affecting 1%-2% of the population (more common in women). Thirty to 35% of cases of CU have angioedema [1]. The etiology of chronic spontaneous urticarial is not usually clear, 40%-50% are idiopathic and 30%-40% are autoimmune [2, 3]. Quality of life in CU is usually disturbed which has a direct relation with severity [4].

Non-infectious uveitis (NIU) is a disorder with various etiologies and is characterized by eye inflammation, mainly affecting people of working age. An accurate diagnosis of NIU is crucial for appropriate therapy. The aim of therapy is to improve vision, relieve ocular inflammation, prevent relapse, and avoid treatment side effects. At present, corticosteroids are the mainstay of topical or systemic therapy. However, repeated injections are required for the treatment of chronic NIU. Recently, new drug delivery systems that may ensure intraocular delivery of therapeutic drug levels have been highlighted. Furthermore, with the development of immunosuppressants and biologics, specific therapies can be selected based on the needs of each patient. Immunosuppressants used in the treatment of NIU include calcineurin inhibitors and antimetabolites. However, systemic immunosuppressive therapy itself is associated with adverse effects due to the inhibition of immune function. In patients with refractory NIU or those who cannot tolerate corticosteroids and immunosuppressors, biologics have emerged as alternative treatments. Thus, to improve the prognosis of patients with NIU, NIU should be managed with different drugs according to the response to treatment and possible side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases that affect the gut and extraintestinal organs. Preliminary evidence has shown that patients with CD or UC are at increased risk of developing intestinal and extraintestinal cancers, therefore, there is an ever-growing concern about the safety of immunomodulators and biologics for these patients. The aim of this review is to summarize the evidence regarding the association between Inflammatory Bowel Disease (IBD) and extraintestinal cancers, and the safety and management of immunomodulators and biologics for patients with IBD and previous or current extraintestinal cancer. Background: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. Aims: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. Results: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. Conclusions: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists. [ABSTRACT FROM AUTHOR]