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Background: Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios. Objective: We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs. Methods: Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs. Results: Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2–3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings. Conclusion: In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Purpose: To document the long-term visual outcomes in patients with Blau syndrome. Methods: A retrospective institutional cohort study was conducted, and 13 patients with genetically confirmed Blau syndrome were included. Demographic and clinical data were collected from standardised medical charts. Baseline was defined as the first detected uveitis and data were recorded onwards at intervals of 1, 3, 5, 10, 15 and 20 years. Results: Anterior uveitis was the most common classification at baseline (57.1%). Among patients with documented uveitis lasting 10 years or more, all of them developed panuveitis. Median logMAR visual acuity at baseline was 0 (range −0.5; 0.7), 0.19 (range 0; 1.5) at year 5, and 0.7 (range 0.1 – no perception of light) at year 20, as recorded in 13, 16, and 10 eyes, respectively. All patients received treatment with topical and oral steroids, and multiple systemic immunosuppressants including biologics. Disease control, defined as having cells <1+ in both eyes and using topical steroid eye drops less than twice daily, was achieved in 14.3% to 37.5% of patients at the different time points. Cataract surgery was performed in 12 eyes of 8 patients, 3 eyes of 3 patients necessitated glaucoma surgery, and 4 eyes of 4 patients required surgery for retinal detachment. Conclusion: Uveitis associated with Blau syndrome commonly leads to severe, chronic panuveitis, requiring long-term systemic immunosuppression. Early diagnosis and timely initiation of biologics may prevent significant visual impairment. [ABSTRACT FROM AUTHOR]

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children. Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children. What is known: • Treatment with anti-TNF inhibitors during pregnancy does not appear to affect serologic response to vaccination in exposed children. • Evidence on the efficacy of vaccination in children exposed to ustekinumab or vedolizumab in utero is almost lacking. What is new: • Our findings suggest that in utero exposure to ustekinumab or vedolizumab does not significantly affect the serological responses to common childhood non-live (tetanus, Haemophilus influenzae B, diphtheria) and live vaccines (measles, mumps, rubella). • No major adverse effects on overall immunological health were observed in children exposed in utero to ustekinumab or vedolizumab. [ABSTRACT FROM AUTHOR]

Guidelines generally recommend a combination of immunological assays and chest X-ray imaging (CXR) when screening for latent tuberculosis infection (LTBI) prior to biologic treatment in inflammatory bowel disease (IBD). To investigate whether CXR identify patients with suspected LTBI/TB who were not identified with QuantiFERON tests (QFT) when screening for LTBI/TB before starting biologic treatment in IBD patients. Single-center, retrospective cohort study of patients with inflammatory bowel disease who had a QFT and a CXR prior to initiation of biologic treatment in a 5-year period (October 1st, 2017 to September 30th, 2022). 520 patients (56% female, mean age 40.1 years) were included. The majority had none or few risk factors for TB (as reflected by the demographic characteristics) but some risk factors for having false negative QFT results (concurrent glucocorticoid treatment and inflammatory activity). QFT results were positive in 8 patients (1.5%), inconclusive in 18 (3.5%) and negative in 494 (95.0%). Only 1 patient (0.19%) had CXR findings suspicious of LTBI. This patient also had a positive QFT and was subsequently diagnosed with active TB. All patients with negative or inconclusive QFT had CXR without any findings suggesting LTBI/TB. One patient developed active TB after having initiated biologic treatment in spite of having negative QFT and a normal CXR at screening. In a population with low risk of TB, the benefits of supplementing the QFT with a CXR are limited and are unlikely to outweigh the cost in both patient test-burden, radioactive exposure, and economic resources. [ABSTRACT FROM AUTHOR]

Background: Trypanophobia or "needle phobia" represents a potential hindrance to the effective management of chronic diseases whenever an injectable therapy might be required, especially in case of frequent administrations. Psoriasis, a chronic dermatologic disease, can be effectively treated with biologic drugs administered subcutaneously. Thankfully, anti‐IL‐23 drugs require few administrations per year and are available in prefilled pens that hide the needle, thus representing a convenient option in patients with trypanophobia. Methods: An observational multicentric study was conducted on patients with moderate‐to‐severe psoriasis who were treated with 75 mg × 2 risankizumab prefilled syringe therapy for more than 6 months and reported a loss of efficacy measured by the Psoriasis Area and Severity Index (PASI) from PASI 90 to PASI 75 attributed to a reduction of adherence due to trypanophobia. The patients were switched to 1 prefilled pen of risankizumab 150 mg and asked to fill out the Self‐Injection Assessment Questionnaire (SIAQ) before and after the injection at week 0 and at the following administration after 12 weeks. Subjects scored each item of the SIAQ on a 5‐point scale, scores were later transformed from 0 (worst experience) to 10 (best experience). Results: Twenty‐two patients were enrolled. The mean SIAQ predose domain scores were 5.5 for feelings about injection, 6.2 for self‐confidence, and 6.4 for satisfaction with self‐injection. After dose scores were higher (> 8.5) for each of the six domains at Week 0 and even higher after 12 weeks (> 9.0). Conclusions: User‐friendly devices, such as prefilled pens, and a lower number of injections improved patient satisfaction in a group of patients with psoriasis on treatment with biologic drugs. We believe that treatment adherence could be positively influenced by such changes in the way of administration of a biologic treatment. [ABSTRACT FROM AUTHOR]

Objectives The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA. Material and methods This was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynu­renine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated. Results The results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynu­renine-to-tryptophan ratio ( p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors ( p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation. Conclusions The RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA – especially for comorbidity of RA and depression.

Abstract Introduction Plaque psoriasis is a common, often debilitating, chronic autoimmune inflammatory skin disease. Moderate-to-severe forms of psoriasis can be treated with biologics such as anti-interleukin and anti-tumor necrosis factor antibodies. We aimed to investigate treatment discontinuation among patients with psoriasis who initiated biologic treatment. Methods We conducted a retrospective, non-interventional cohort study based on anonymized claims data from the German statutory health insurance which covered the years from 2016 to 2021. We included adult patients with psoriasis who initiated biologic treatment in drug-specific cohorts. Over a 365-day follow-up period, we assessed the frequencies and the time until treatment discontinuation for different biologics. Differences in discontinuation rates were compared using a multivariate Cox proportional hazards model. Results A total of 2565 patients with psoriasis who initiated treatment with secukinumab (n = 612), adalimumab (n = 454), guselkumab (n = 354), ixekizumab (n = 259), ustekinumab (n = 241), tildrakizumab (n = 205), brodalumab (n = 166), risankizumab (n = 145), etanercept (n = 91), certolizumab (n = 29), and infliximab (n = 9) were included. A total of 1290 patients (50.29%) discontinued treatment during the follow-up period, ranging from 30.34% (risankizumab) to 69.23% (etanercept). Median time until discontinuation of treatment ranged from 102 days (etanercept) to 208 days (risankizumab). Once the biologic treatment was discontinued, 45.05% of patients restarted the treatment with the same agent, 23.10% of patients switched to another biologic, and 31.86% received no further biologic agent. Compared to patients treated with risankizumab, the treatment discontinuation rate was significantly higher (p

Introduction: The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA. Material and methods: This was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynurenine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated. Results: The results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynurenine- to-tryptophan ratio (p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors (p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation. Conclusions: The RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA - especially for comorbidity of RA and depression. [ABSTRACT FROM AUTHOR]

Objectives Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive SSc compared with CYC. CYC, however, does not provide a long-term benefit in SSc. The combination of MMF and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. Methods Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease >25% or an FVC increase >10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. Results Twenty-one SSc patients in the combination therapy group were compared with 16 in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (P  = 0.7). The hazard ratio for EFS at 24 months favoured the combination group (HR = 0.09, P  = 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. Conclusion MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months. [ABSTRACT FROM AUTHOR]

Introduction: Plaque psoriasis is a common, often debilitating, chronic autoimmune inflammatory skin disease. Moderate-to-severe forms of psoriasis can be treated with biologics such as anti-interleukin and anti-tumor necrosis factor antibodies. We aimed to investigate treatment discontinuation among patients with psoriasis who initiated biologic treatment. Methods: We conducted a retrospective, non-interventional cohort study based on anonymized claims data from the German statutory health insurance which covered the years from 2016 to 2021. We included adult patients with psoriasis who initiated biologic treatment in drug-specific cohorts. Over a 365-day follow-up period, we assessed the frequencies and the time until treatment discontinuation for different biologics. Differences in discontinuation rates were compared using a multivariate Cox proportional hazards model. Results: A total of 2565 patients with psoriasis who initiated treatment with secukinumab (n = 612), adalimumab (n = 454), guselkumab (n = 354), ixekizumab (n = 259), ustekinumab (n = 241), tildrakizumab (n = 205), brodalumab (n = 166), risankizumab (n = 145), etanercept (n = 91), certolizumab (n = 29), and infliximab (n = 9) were included. A total of 1290 patients (50.29%) discontinued treatment during the follow-up period, ranging from 30.34% (risankizumab) to 69.23% (etanercept). Median time until discontinuation of treatment ranged from 102 days (etanercept) to 208 days (risankizumab). Once the biologic treatment was discontinued, 45.05% of patients restarted the treatment with the same agent, 23.10% of patients switched to another biologic, and 31.86% received no further biologic agent. Compared to patients treated with risankizumab, the treatment discontinuation rate was significantly higher (p < 0.05) in patients treated with the other biologics except ustekinumab (p = 0.12). Conclusions: Further research should explore reasons leading to treatment discontinuation in order to support treatment choices for patients with moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. Methods Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. Results Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02–1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05–1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74–0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. Conclusions Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.

Background: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. Methods: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. Results: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02–1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05–1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74–0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. Conclusions: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: Biologic therapies have demonstrated benefits for individuals with severe asthma, including reduced daily symptoms and severe exacerbations. However, data describing patient perspectives on these treatments are limited. This study sought to understand the preferences and priorities of Canadians with severe asthma in the context of novel biologic treatment options. Methods: Semi-structured, qualitative interviews were conducted among Canadians with severe asthma from July to August 2022. Purposeful sampling included individuals with and without biologic therapy experience. All participants described daily life with severe asthma, experiences and priorities related to asthma treatment and their impressions of biologics. Reflexive thematic analysis was used to explore patterns in the data. Results: Among 18 individuals included, 10 were currently taking or had prior experience with biologic treatment for asthma. Those who had never been treated with biologics were unfamiliar with them, considering treatment, or believed that they may not be eligible. Four themes were developed to convey the perspectives of participants on biologics: (1) life-changing benefits, but not for all; (2) navigating barriers to being prescribed and remaining adherent to biologic treatments; (3) treatment administration preferences are not only about convenience; (4) concerns about safety and the unknown as a source of treatment hesitancy. Conclusions: Findings suggest that the clinical benefits of biologics align with patient perceptions of achieving good asthma control. However, treatment gaps persist among individuals who do not experience a meaningful improvement in their asthma symptoms and those who face barriers accessing biologics. People with severe asthma attributed importance to greater availability of at-home treatment options, improved access to financial support to cover treatment costs and support to address safety concerns. This research provides insight into patient-based treatment priorities and preferences for biologics, which may help inform decision-making related to emerging therapies for severe asthma. Plain Language Summary: For people with severe asthma, biologics are a treatment option that can be taken in addition to their regular medication. In this study, we asked 18 Canadians with severe asthma about how having severe asthma affects their lives, their current and previous asthma treatments, and their views on biologics. Ten people in this study were currently taking or had previously taken biologics for severe asthma. We found that biologics can be life changing. Also, people with severe asthma can find it difficult to get on and stay on biologics. They would like financial and educational support when considering biologics and prefer to take biologics at home, if possible. This study helps us understand the priorities and preferences related to biologics of patients with severe asthma. [ABSTRACT FROM AUTHOR]

Evidence of effectiveness and safety in combined therapies is scarce and based on case reports and small case series. We report a case of dual biologic therapy with ustekinumab and dupilumab in a patient with severe Crohn disease and atopic dermatitis. There was no interference between these drugs after a 7‐month follow‐up. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Material and methods Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder (“overt CVD”), any traditional CV risk factor (“atCVrisk”) and no CV risk factor (“vlCVrisk”) groups. Results Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk ( n = 8, 4.2%) or overt CVD ( n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02–1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04–1.18; p < 0.01), but not ever smoking ( p = 0.93), male sex ( p = 0.26), positive RF ( p = 0.24), positive ACPA ( p = 0.90), or baseline disease activity ( p = 0.19), were independent predictor of incident CV risk factors. Conclusions Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse long-term prognosis.

Abstract Background Some patients treated with biologic therapy for psoriasis experience adverse events causing treatment discontinuation. Objectives To identify predictors of adverse events resulting in discontinuation of biologics for psoriasis. Methods This cohort study involved data from the Danish nationwide registry DERMBIO. A classification algorithm based on gradient‐boosted decision trees combined with a mixed‐effects model was applied to data on various drugs to predict treatment discontinuation caused by adverse events and to identify important predictors. Results This study comprised 4876 treatment series, including 3078 (63.1%) that were discontinued. With adverse events causing 19.6% of these, it was the second most frequent reason for discontinuation following ineffectiveness. The proportion of treatments discontinued due to adverse events was 20.0% [16.7%, 23.9%; 95% confidence interval (CI)] among patients that had discontinued their previous treatment series due to adverse events, and 11.6% [10.3%, 13.1%; 95% CI] among treatment series where the previous treatment was discontinued due to other reasons (p

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Generalized pustular psoriasis (GPP) is a form of pustular psoriasis that is distinguished by recurring or persistent outbreaks of non‐acral primary sterile pustules. These eruptions can occur with or without systemic inflammation. Various factors, such as medications, stress and viral infection, have been identified as potential triggers for GPP flares. While several cases have detailed GPP‐like eruptions in the setting of coronavirus disease 2019 (COVID‐19) infection, few have explored the interplay between infection and biologic use in the development of GPP. In this case, we detail the history and management of a 45‐year‐old male patient with a prior history of spondyloarthropathy managed on a tumour necrosis factor‐α inhibitor and recent COVID‐19 infection presenting with a new, spreading pustular rash. [ABSTRACT FROM AUTHOR]

Introduction: Introduction of novel biologic treatments for plaque psoriasis has revolutionized treatment approach and improved outcomes in patients with moderate-to-severe disease. New groups of biologics are even more effective and better tolerated compared to their predecessors. However, none of the currently available biologic drugs is associated with complete skin clearance in all treated patients. Moreover, the requirement to stop therapy in accordance with previous therapeutic program guidelines in Poland may have contributed to a gradual loss of efficacy of biologic drugs. Betamethasone dipropionate (BD) and calcipotriol (CAL) foam is the most widely studied topical drug in the therapy of mild forms of psoriasis. Numerous clinical trials have demonstrated its excellent efficacy not only in reactive therapy but also in preventing recurrences through the implementation of proactive therapeutic regimens. Case reports: We present two cases of patients with severe psoriasis and psoriatic arthritis who were treated with biologic drugs with incomplete remission of skin lesions. Topical therapy with BD/CAL foam was introduced to treat refractory psoriatic lesions, leading to excellent outcomes. Conclusions: The reported cases show that therapy with BD/CAL foam may be an effective adjuvant treatment of psoriasis in cases of incomplete and unsatisfactory response to systemic therapies, including biologics. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Material and methods: Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder (“overt CVD”), any traditional CV risk factor (“atCVrisk”) and no CV risk factor (“vlCVrisk”) groups. Results: Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk (n = 8, 4.2%) or overt CVD (n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02–1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04–1.18; p < 0.01), but not ever smoking (p = 0.93), male sex (p = 0.26), positive RF (p = 0.24), positive ACPA (p = 0.90), or baseline disease activity (p = 0.19), were independent predictor of incident CV risk factors. Conclusions: Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse longterm prognosis. [ABSTRACT FROM AUTHOR]

Objective. The study aimed at characterizing the evolution of RA treatment with b/tsDMARDs in Romania, since the end of the SARS-CoV-2 pandemic and the national approval of JAKi. Methods. Data on RA patients was obtained from the Romanian Registry of Rheumatic Diseases database between January 1st, 2022, and December 31st, 2022, encompassing all Romanian RA patients fulfilling the national criteria for b/ tsDMARD initiation. Results. The RRBR database contained 5396 active RA patients: 83.2% female, 59.9 years mean age, 13 years median disease duration, 86.7% RF positive, 81.7% ACPA positive, with a high prevalence of cardiovascular comorbidities, 89.8% receiving at least one csDMARD, most often methotrexate (48.7%), with 6.3% on glucocorticoids, 78.8% on bDMARDs (especially etanercept - 27.6%, adalimumab - 18.1% and tocilizumab - 14.0%) and 21.2% on JAKi (most often on baricitinib - 11.4%), with a 58.2% DAS28-defined remission rate and a 34.3% SDAI-defined remission rate. Conclusion. The Romanian cohort of RA patients on b/tsDMARDs observed the both classical phenotypic characteristics of RA and local cohort characteristics. JAKi prescription has gained a significant increase. Capturing data on real-world patients filtered by stringent criteria for high disease activity and poor prognosis factors, the RRBR database proves to be an extremely useful insight into the evolution of RA pharmacologic treatment.

CD (cluster of differentiation) 69 and CD25 are considered early and late markers of the activation of lymphocytes, respectively. CD25 is a part of the IL-2 receptor and is present on the surface of immune and non-immune cells, with high amounts on activated lymphocytes and regulatory T cells. CD69 is expressed on various types of white blood cells, including newly activated lymphocytes, lymphocytes infiltrating tissues isolated from subjects with chronic auto-inflammatory diseases, several subtypes of memory T cells and regulatory T cells. Primarily, CD69 was considered to be an early marker of the activation of lymphocytes, but, right now, data derived from in vitro and in vivo studies have revealed the immunomodulatory role of this surface antigen. In 84 patients with psoriasis, of whom 28 were treated with different biologic drugs, as well as in 29 healthy control subjects, the expression of CD25 and CD69 on different subtypes of peripheral blood mononuclear cells (PBMCs) was studied with the use of flow cytometry. Significantly higher levels of CD3/CD69-, CD8/CD69- and CD19/CD69-positive PBMCs as well as within CD3+ cells were present in subjects suffering from psoriasis when compared to healthy controls. In patients with psoriasis who were treated with biologic drugs, the levels of CD3/CD69-, CD4/CD69- and CD19/CD69-positive PBMCs, and CD3/CD69 within CD3+ cells, CD4/CD69 within CD4+ cells, CD4/CD25 within CD4+ cells and CD19/CD69 within CD19+ cells were significantly higher than before therapy. Our results support a role for activation markers, especially CD69, in psoriasis. Further research is warranted to fully clarify their significance in this common dermatosis, especially during biologic treatment. [ABSTRACT FROM AUTHOR]

In the context of COVID-19 pandemic, a consistent medical concern raised among severe asthma patients, though the studies excluded an increased risk of severe disease as well as an increased susceptibility. The aim of the study was to apply the Psychological General Well-Being Index (PGWBI) questionnaire to severe asthmatics during the COVID-19 pandemic and to evaluate the data with a hierarchical cluster analysis. 114 severe asthmatics were asked to respond anonymously to the PGWBI questionnaire. The patients underwent a lung functional test, fractional exhaled nitric oxide (FeNO) measurement, Asthma Control Test (ACT), and Asthma Control Questionnaire (ACQ6). A hierarchical cluster analysis was performed using an agglomerative approach and complete linkage to evaluate the results. The study population predominantly included female (60%), middle-aged patients, with normal lung function parameters, mild signs of airway, and satisfactory asthma control. The PGWBI score (82.46 ± 16.53) of the study population showed a good state of psychological well-being and was similar to that of a representative sample of healthy adult Italian subjects. Thus, Hierarchical cluster analysis identified 3 groups of patients: Cluster 1 (32%), Cluster 2 (64%), and Cluster 3 (4%). Whilst the Cluster 2 patients' PGWBI score fell within the normal range, the Cluster 1 patients had a significantly lower total score (68.57 ± 7.2; p < 0.05), suggesting moderate distress. The Cluster 3 patients presented a total score markedly low. Although the majority of the severe asthma patients studied demonstrated good mental well-being during the COVID-19 pandemic, some did indeed show moderate to severe psychological distress. [ABSTRACT FROM AUTHOR]

Background: Glenohumeral osteoarthritis (GOA) is associated with disabling shoulder pain that affects everyday life. Its management comprises various treatment approaches, both conservative and surgical. Regenerative medicine has gained a major role in the conservative treatment of osteoarthritis. Intra-articular injection of adipose-derived mesenchymal stem cells (ADMSCs) is a widely used regenerative medicine approach. The aim of this retrospective study was to report the safety and clinical outcomes of intra-articular injection of ADMSCs in patients with GOA over 36-months. Methods: This retrospective observational study involved patients with chronic shoulder pain resistant to standard conservative treatment and a diagnosis of concentric GOA, who received an intra-articular injection of autologous micro-fragmented adipose tissue (μFAT). The values of the Constant–Murley score (CMS), the visual analog scale (VAS), and the simple shoulder test (SST), collected at baseline and at 12, 24, and 36 months, were analyzed to assess treatment efficacy. The single assessment numeric evaluation (SANE) was used to rate patient satisfaction. The Friedman test was used to compare observations of CMS, VAS, and SST values repeated on the same subjects. The significance threshold was set at 0.05. Results: The participants were 65 patients with a mean age of 54.19 years and a nearly equal gender distribution. Most had mild concentric GOA classified as Samilson–Prieto grade 1. The mean follow-up duration was 44.25 months. The postoperative clinical scores showed significant improvement. At 36 months, the CMS was 84.60, the VAS score was 3.34, and the SST score was 10.15 (all p < 0.0001). The SANE score at 36 months indicated that 54 patients (83.08%) were completely satisfied with the treatment. Conclusion: ADMSC treatment exerted favorable effects on the clinical outcomes of patients with GOA, providing pain relief and improving shoulder function. Our data support its use as a conservative treatment option for osteoarthritis. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory skin disease which is characterized by painful, recurrent nodules and abscesses. The overall prevalence of HS is estimated to be 11 per 100 000 individuals in the United States and 4% of the world's population. Women are three times more affected than men, especially patients between 18 and 29 years. Similarly to acne vulgaris, HS is primarily associated with follicular occlusion, which results from a number of biological processes, including follicular epithelial hyperplasia and hyperkeratinization. There are numerous available treatment options for cutaneous lesions in the course of HS. A combination of conservative therapy and appropriate surgical treatment conducted by an experienced surgeon ensures the best possible clinical outcomes. Presently, biologic therapy is the most effective pharmacological treatment in patients with a moderate-to-severe course of the disease. Numerous ongoing clinical trials provide hope for greater availability of new biologic therapy methods. [ABSTRACT FROM AUTHOR]

Abstract Microplastics are currently known to be among the most detrimental environmental. The research on ways to counteract these pollutions and the use of microorganisms for the biological decomposition of various plastic polymers have evolved over the recent years. In this regard, the present study collected effluents from the southern Tehran treatment plant and separated and counted the microplastics present in them, it was found that the least number of microplastics was found in the samples of the summer season and the highest number of microplastics was found in the samples of the spring season. In these samples, particles could be identified in three forms: fiber, fragment, and film, which revealed that the most frequently observed microplastics were polypropylene and then polyethylene. These microplastics combine with the microbes in the culture medium. Three microbial colonies that survived were then separated and identified, which revealed that these bacteria included Achromobacter denitrificans (sample B), Bacillus amyloliquefaciens (sample C), and Pseudomonas aestusnigri (sample E). Moreover, the decomposition of polypropylene and polyethylene microplastics exposed to isolates was examined through various methods. Results of cellular gravity examination indicated that the average weight reduction in the PP sample exposed to B and E bacterial isolates was 38.2% and 58.9%, respectively. In the SEM images, the surface of the polymers of these two isolates is more uneven. Moreover, the mean cellular weight reduction for PE-based microplastic exposed to isolate C was 13.3%, the results of FT-IR tests showed that the peaks in the samples exposed to strains B and E were accompanied by changes compared to the control sample (G). The results of the TGA test also confirm the greater effectiveness of the bacterial strain E. It was based on the polymer structure. In the Raman spectrum of sample E, some peaks have been removed and new peaks with other shifts have appeared in their place. Results were confirmed by carbon dioxide emission tests and the produced protein amount.

The management of psoriatic disease in human immunodeficiency virus (HIV)-positive patients is challenging. Psoriasis in HIV-positive patients is often severe, progressive, and resistant to first- and second-line therapies, including topical treatments, phototherapy, highly active antiretroviral therapy (HAART), and oral retinoids. Other systemic agents used to treat psoriasis, such as methotrexate and cyclosporine, are immunosuppressants and thus many dermatologists may not feel comfortable prescribing them to HIV-positive patients who are already immunocompromised. Biologic agents, which target specific aspects of overactive immune pathways in psoriasis, have revolutionized the management of moderate-to-severe psoriasis. However, data is limited regarding their safety and efficacy in HIV-positive patients.ObjectiveReport four cases of HIV-positive patients managed on biologic therapy and summarize the cases of psoriasis in HIV-positive patients managed on biologic therapy that have been published in dermatologic literature to date.MethodsWe searched PubMed and Embase databases using the terms HIV and psoriasis or HIV and psoriatic arthritis combined with one of the eleven biologics currently approved for treating psoriasis.ResultsWe identified 48 cases of anti-psoriasis biologic therapy (including adalimumab, infliximab, etanercept, ustekinumab, and guselkumab) in HIV-positive patients and added four. While data is limited, the evidence available suggests biologic agents are safe and efficacious in moderate-to-severe psoriasis and may even have a favorable effect on CD4 and HIV viral counts when used with concomitant HAART.ConclusionFurther research would be helpful to establish practical guidelines for the use of anti-psoriasis biologic therapy in the HIV population, including that of newer agents.

Background: B cells are central to the pathogenesis of systemic lupus erythematosus (SLE). We aimed to analyze the efficacy and safety of new B cell-targeted drug therapies for SLE. Methods: A systematic review of randomized controlled trials (RCTs) and reference lists of relevant articles published from inception to 2022 were selected from PubMed, Scopus and Web of Science databases. Random effects meta-analyses were performed to estimate an overall effect size for the risk of adverse events (AEs) and serious adverse events (SAEs) with belimumab and tabalumab treatment. Heterogeneity was assessed using the I2 statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test. Results: This study included 13 RCTs, of which three showed high risk of bias. Egger's test showed no asymmetry. The risk of SAEs and AEs was lower in the treatment group with belimumab treatment. The risk of AEs for tabalumab treatment was lower in the treatment group and lower for SAEs. Conclusion: Belimumab and tabalumab therapies are effective and safe in the treatment of SLE, although tabalumab does not show sufficient statistical power. Advances in understanding the underlying mechanisms of SLE will be directed towards correlating clinical manifestations with specific pathogenic pathways and the development of precision medicine. [ABSTRACT FROM AUTHOR]

• HepB-CpG is an immune adjuvanted vaccine that has not been used previously in patients who require chronic use of immunosuppressive medications. • Two groups of medically immunosuppressed patients were given either 2 or 3 doses of the vaccine as per protocol. • Patients taking low potency immunosuppressive drugs had more rapid and higher anti-HBs concentrations generally after 2 doses of the vaccine. • Patients taking moderate potency immunosuppressive drugs had a slower antibody response and generally required 3 doses of the vaccine. • Antibody responses to HepB-CpG were better compared to historical cohorts vaccinated with traditional recombinant HBV vaccine. Immunosuppressed patients are a targeted group for HBV vaccination but suboptimal antibody responses occur when traditional recombinant vaccines are used. We tested an FDA approved immune adjuvanted HBV vaccine (HEPLISAV--B® or HepB-CpG) in medically immune suppressed individuals. HepB-CpG was given to 10 patients taking biologic agents or anti-rejection therapy. Each received vaccine at time 0 and week 4 with a third dose at week 12 if anti-HBs remained less than 10 mIU/mL. Seroprotective anti-HBs developed in 70 % of participants by week 24. Those taking biologic agents responded more rapidly and a third dose was generally needed in those transplanted. By week 24, most taking biologics but only 2 of 6 on anti-rejection treatment had antibody levels exceeding 100 mIU/mL. Seroprotective anti-HBs developed in 70 % with HepB-CpG. Antibody responses were more rapid in those taking biologic agents but a third dose improved antibody responses in transplanted participants. [ABSTRACT FROM AUTHOR]

The programmed death-1 (PD-1) receptor plays a major physiological role in the maintenance of immune tolerance and, by interaction with its ligands (PD-L1 and PD-L2), prevents the development of multiple immune-mediated diseases. There is growing evidence of the PD-1/PD-L1 pathway playing an important role in the pathogenesis of psoriasis. In total, 84 subjects with psoriasis were included in this study, together with 29 healthy subjects as a control group. Twenty-eight of the psoriatic patients were treated with biologic therapy (TNF-alpha, interleukin (IL)-12/23, or IL-17 inhibitors). The amounts of PD-1- and PD-L1-positive T-cells in peripheral blood were evaluated using flow cytometry. Significantly lower levels of peripheral blood mononuclear cells (PBMCs) with the expression of PD-1 and PD-L1 were found in psoriatic patients compared to healthy individuals, i.e., CD3/PD-1-, CD3/PD-L1-, CD4/PD-1-, CD4/PD-L1-, CD8/PD-L1-, CD19/PD-1-, and CD19/PD-L1-positive cells. Biologic treatment resulted in the elevation of CD3/PD-L1- and CD8/PD-L1- and a decrease in CD8/PD-1-positive PBMCs. Our results confirm previous observations of the PD-1/PD-L1 pathway being disrupted in psoriasis, and that these disturbances may play an important role in development of the disease. Biologic drugs may reverse several abnormalities observed within this pathway, which may explain their excellent efficacy in the treatment of psoriasis. Further research should be conducted to fully explain the results obtained. [ABSTRACT FROM AUTHOR]

Objective. The study aimed at characterizing the evolution of RA treatment with b/tsDMARDs in Romania, since the end of the SARS-CoV-2 pandemic and the national approval of JAKi. Methods. Data on RA patients was obtained from the Romanian Registry of Rheumatic Diseases database between January 1st, 2022, and December 31st, 2022, encompassing all Romanian RA patients fulfilling the national criteria for b/ tsDMARD initiation. Results. The RRBR database contained 5396 active RA patients: 83.2% female, 59.9 years mean age, 13 years median disease duration, 86.7% RF positive, 81.7% ACPA positive, with a high prevalence of cardiovascular comorbidities, 89.8% receiving at least one csDMARD, most often methotrexate (48.7%), with 6.3% on glucocorticoids, 78.8% on bDMARDs (especially etanercept - 27.6%, adalimumab - 18.1% and tocilizumab - 14.0%) and 21.2% on JAKi (most often on baricitinib - 11.4%), with a 58.2% DAS28-defined remission rate and a 34.3% SDAI-defined remission rate. Conclusion. The Romanian cohort of RA patients on b/tsDMARDs observed the both classical phenotypic characteristics of RA and local cohort characteristics. JAKi prescription has gained a significant increase. Capturing data on real-world patients filtered by stringent criteria for high disease activity and poor prognosis factors, the RRBR database proves to be an extremely useful insight into the evolution of RA pharmacologic treatment. [ABSTRACT FROM AUTHOR]

Microplastics are currently known to be among the most detrimental environmental. The research on ways to counteract these pollutions and the use of microorganisms for the biological decomposition of various plastic polymers have evolved over the recent years. In this regard, the present study collected effluents from the southern Tehran treatment plant and separated and counted the microplastics present in them, it was found that the least number of microplastics was found in the samples of the summer season and the highest number of microplastics was found in the samples of the spring season. In these samples, particles could be identified in three forms: fiber, fragment, and film, which revealed that the most frequently observed microplastics were polypropylene and then polyethylene. These microplastics combine with the microbes in the culture medium. Three microbial colonies that survived were then separated and identified, which revealed that these bacteria included Achromobacter denitrificans (sample B), Bacillus amyloliquefaciens (sample C), and Pseudomonas aestusnigri (sample E). Moreover, the decomposition of polypropylene and polyethylene microplastics exposed to isolates was examined through various methods. Results of cellular gravity examination indicated that the average weight reduction in the PP sample exposed to B and E bacterial isolates was 38.2% and 58.9%, respectively. In the SEM images, the surface of the polymers of these two isolates is more uneven. Moreover, the mean cellular weight reduction for PE-based microplastic exposed to isolate C was 13.3%, the results of FT-IR tests showed that the peaks in the samples exposed to strains B and E were accompanied by changes compared to the control sample (G). The results of the TGA test also confirm the greater effectiveness of the bacterial strain E. It was based on the polymer structure. In the Raman spectrum of sample E, some peaks have been removed and new peaks with other shifts have appeared in their place. Results were confirmed by carbon dioxide emission tests and the produced protein amount. [ABSTRACT FROM AUTHOR]

The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient's age and duration of psoriasis at several timepoints throughout the observation period. [ABSTRACT FROM AUTHOR]

Background: Real-life studies evaluating the long-term efficacy of guselkumab in moderate-to-severe psoriasis in China are limited and not available. Methods: In this real-life study, we retrospectively examined a total of 27 patients with moderate-to-severe psoriasis treated with guselkumab [100 mg, subcutaneous (s.c.)] with a follow-up period of at least 52 weeks in a real-life setting conducted at the Department of Dermatology, Xiangya Hospital, Central South University and Department of Psoriasis, Dalian Dermatosis Hospital. The primary endpoint of the study was long-term effectiveness [reduction of Psoriasis Area and Severity Index (PASI) score, improvement of Dermatology Life Quality Index (DLQI)], safety, and tolerability of guselkumab. Results: Guselkumab treatment decreased the mean PASI score from 12.46 ± 6.34 at baseline to 4.03 ± 3.25 (P < 0.001) and 0.77 ± 1.25 (P < 0.001) at 12 and 52 weeks. At 12 weeks, PASI 75, 90, and 100 response was achieved in 44.4%, 18.5%, and 11.1% of patients, respectively. At 1 year, PASI 75, 90, and 100 response was achieved in 88%, 72%, and 48% of patients, respectively. At 52 weeks, 96% of patients achieved a PASI score of ≤ 3 and 80% of patients achieved DLQI (0/1). No patients withdrewed from the study due to primary or secondary ineffectiveness or failure to adhere to the medication. During the follow-up period, only two adverse events were reported (tinea capitis and diarrhea). Conclusions: Our findings confirm that guselkumab is an appropriate therapeutic option in routine clinical practice, particularly when treating sophisticated patients with comorbidities or who failed to previous biologic therapy. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease potentially elevates the risk of infections, independently from age, while the disease activity and medical treatment(s) can also increase the risks. Nevertheless, it is necessary to clarify these preconceptions as well during the COVID-19 pandemic. Methods: An observational, questionnaire based study was conducted in Hungary between February and August 2021. 2 questionnaires were completed. The first questionnaire surveyed the impact of the pandemic on patients with biologic treatments and assessed the severity and outcome of the infection, whereas the second one assessed vaccination rate and adverse events. Results: 472 patients participated in the study. 16.9 % of them acquired the infection and 6.3 % needed hospitalization. None of them required ICU care. Male sex elevated the risk of infection (p = 0.008), while glove (p = 0.02) and mask wearing (p = 0.005) was the most effective prevention strategy. Nevertheless, abstaining from community visits or workplace did not have an impact on the infection rate. Smoking, age, and disease type did not elevate the risk. UC patients had poorer condition during the infection (p = 0.003); furthermore, the disease activity could potentially worsen the course of infection (p = 0.072). The different biological treatments were equally safe; no difference was observed in the infection rate, course of COVID-19. Azathioprine and corticosteroids did not elevate the infection rate. 28 patients (35.0 %) suspended the ongoing biologic treatment, but it had no impact on the disease course. However, it resulted in changing the current treatment (p = 0.004). 9.8 % of the respondents were sceptic about being vaccinated, and 90 % got vaccinated. In one case, a serious flare-up occurred. Discussion: Most patients acquired the infection at workplace. Biologic therapies had no effect on the COVID-19 infection, whereas male sex, an active disease, and UC could be larger threat than treatments. Vaccination was proved to be safe, and patient education is important to achieve mass vaccination of the population.

Therapeutic options for psoriasis vulgaris have changed during recent decades with the introduction of biologics. Few nationwide studies are available on psoriasis treatment patterns, and those from Finland predate the use of biologics. The aim of this retrospective, population-based registry study was to identify patients with psoriasis vulgaris and their treatment patterns in the secondary care setting in Finland. The study cohort included 41,456 adults with a diagnosis of psoriasis vulgaris in the public secondary healthcare setting from 2012 through 2018. Data on comorbidities, pharmacotherapy, and phototherapy were collected from nationwide healthcare and drug registries. Patients in the cohort had a wide range of comorbidities, with 14.9% having psoriatic arthritis. Treatment was based largely on topical and conventional systemic medications. Conventional medications were used by 28.9% of patients, and methotrexate was the most common option (20.9%). Biologics were used by 7.3% of patients, mostly as second- and third-line treatment. The use of conventional systemic medications, topical treatments, and phototherapy decreased after the initiation of biologics. This study of psoriasis vulgaris in Finland provides a framework for the development of future care practices.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology‐based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)‐derived exosomes was confirmed by the CCK‐8 assay (p < 0.05) on CHL‐1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 μg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL‐1 cells) treated with CBSC‐derived exosomes, both the cytotoxicity of CHL‐1 cells treated with CBSC‐derived exosomes exhibited a significant time‐dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let‐7 family of miRNAs, including let‐7a‐5p, let‐7b‐5p, let‐7c‐5p, let‐7d‐3p, let‐7d‐5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL‐1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy. [ABSTRACT FROM AUTHOR]

Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. Insurance claims data (11/2016–6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). In all cohorts (mean age 51–53 years; 67–70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53–68% (p <.001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p <.001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p <.001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation. Benralizumab is a biologic approved as an add-on treatment for severe eosinophilic asthma. Previous real-world studies and clinical trials have shown that benralizumab can reduce the rate of asthma exacerbations and systemic corticosteroid use. However, there is little information on the economic value of benralizumab in real-world patient populations. This study showed that patients with severe asthma in the United States had lower rates of asthma exacerbations after starting treatment with benralizumab. The patients also had fewer asthma exacerbation-related hospitalizations, emergency department visits, and outpatient visits as well as lower medical costs related to asthma exacerbations compared with before the treatment. These benefits were observed in patients who had never taken and those who had been previously treated with biologic therapies, and for up to 24 months after starting benralizumab treatment. These results show that the clinical value of benralizumab translates into reduced medical utilization for patients with severe asthma. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis and its treatments may predispose patients to various infections. This is considered one of the most significant complications in patients with psoriasis. Objectives: In the present study, we aimed to determine the prevalence of infection in hospitalized psoriasis patients and its relationship with systemic and biologic treatments. Methods: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran, were studied and cases of infection were recorded. Results: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis were significantly associated with infection in psoriatic patients. Those patients who received prednisolone had a higher risk of infection, and those under treatment with methotrexate or infliximab had a lower risk of infection. Conclusion: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection. This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids was associated with a higher risk of infection, while using methotrexate or infliximab was concomitant with a lower risk of infection.

Aim We aimed at assessing the published literature on different prophylactic screening and vaccination options in inflammatory bowel disease (IBD) patients between 1980 and 2020. Special attention was attributed to latest data assessing covid-19 vaccinations. Methods We have queried PubMed for all available IBD-related entries published during 1980–2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors’ affiliations. Two gastrointestinal specialists decided by consensus on a list of terms to classify entries. The terms belonged to four treatment groups: opportunistic infections, prophylactic screening, prophylactic vaccinations/treatment, and routine vaccines. Annual trends of publications for the years 1980–2020 were plotted for different screening, vaccinations and infection types. Slopes of publication trends were calculated by fitting regression lines to the annual number of publications. Results Overall, 98,339 IBD entries were published between 1980 and 2020. Of those, 7773 entries belonged to the investigated groups. Entries concerning opportunistic infections showed the sharpest rise, with 19 entries and 1980 to 423 entries in 2020 (slope 11.3, p

Data regarding the willingness of patients affected by inborn errors of immunity to accept vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Therefore, this study assessed SARS-CoV-2 vaccination coverage and hesitancy in immunodeficient patients by surveying adults with primary immune deficiencies and autoinflammatory and rheumatic diseases on biologic therapy. The study was conducted from September 20, 2021, to January 22, 2022, when the primary coronavirus disease 2019 (COVID-19) vaccinations were available to all adults in Poland. We included 207 participants consecutively recruited from five referral centers (57% female; median age: 42.6 [range: 18-76, standard deviation ± 14.70] years). Overall, 55% (n = 114), 17% (n = 36), and 28% (n = 57) of the patients had primary immune deficiencies, autoinflammatory diseases, and rheumatic diseases, respectively. Among the entire cohort, 168 patients (81%) were vaccinated, and 82% were willing to receive a booster dose. Patients with autoinflammatory diseases had the highest vaccination rate (94.4%). A strong conviction that it was the correct decision (72%), fear of getting COVID-19 (38%), and expert opinions (34%) influenced the decision to vaccinate. Among the unvaccinated patients, 33.3% had primary or vocational education (p <0.001). Furthermore, only 33% believed they were at risk of a severe course of COVID-19 (p = 0.014), and 10% believed in vaccine efficacy (p <0.001). They also doubted the safety of the vaccine (p <0.001) and feared a postvaccination flare of their disease (p <0.001). Half of the unvaccinated respondents declared that they would consider changing their decision. Vaccination coverage in immunodeficient patients was higher than in the general Polish population. However, the hesitant patients doubted the vaccine's safety, feared a post-vaccination disease flare, and had primary or vocational education. Therefore, vaccination promotion activities should stress personal safety and the low risk of disease flares due to vaccination. Furthermore, all evidence must be communicated in patient-friendly terms. [ABSTRACT FROM AUTHOR]

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Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009–2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009–2011, 2012–2013, 2014–2015, 2016–2018). In the subgroup of patients starting a first b/tsDMARD 2009–2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009–2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group. [ABSTRACT FROM AUTHOR]