Non-biologic Therapy Research Articles

THE BENEFITS OF NON-BIOLOGICAL THERAPY IN CHILDREN WITH AUTISM SPECTRUM DISORDER (ASD)

Introduction – Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders characterized by three main problems, namely the presence of communication disorders, impaired reciprocal social interaction with the surrounding environment, and restricted, repetitive, and stereotyped behavior patterns in the first 3 years of age. In Indonesia, there were around 112,000 ASD sufferers in 2012, while in 2015 it was estimated that 1 in 250 children had ASD, or around 134,000 people. Methods – The author used the literature review method by collecting the results of several kinds of literature on ASD, and non-biological therapy and their benefits in ASD children. The literature on non-biological therapy and its benefits in ASD children is limited to 2011-2021. Results – Autism is a lifelong disorder, so it is important to recognize it as early as possible, and parents need to understand the problem. It's important to remember that the cause of autism is unknown, and no single drug has been found that can cure ASD, but some therapies can suppress ASD symptoms that can help ASD lead a more productive life by reducing symptoms and improving skills. Discuss – There is no definitive therapy that can cure ASD, but therapy is aimed at improving ASD symptoms. Non-biological therapy which includes behavioral therapy (such as TEACCH or ABA) is currently used as first-line therapy for ASD. Conclusion – Symptoms that appear in ASD children vary widely, therefore the therapy given is individual and depends on the circumstances and symptoms that appear. There are many types of non-biological therapies for ASD, such as ABA, TEACCH, PECS, Caregiver-mediated Intervention, Parent-mediated Communication, SIT, and AIT. These therapies have been shown to have benefits in improving ASD symptoms such as communication skills, social interaction, and behavior, where each therapy has different benefits in each type. These therapies are given to everyone as needed. Keywords: non-biological, children, autism.

Current Treatments for Generalized Pustular Psoriasis: A Narrative Summary of a Systematic Literature Search.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

644 - Effectiveness and safety of upadacitinib in adolescent and adult patients with atopic dermatitis: an interim analysis of week 20-32 data from a real-world multicenter retrospective review

Abstract Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), a selective oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), there is still a lack of real-world evidence. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at weeks 20-32. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints evaluated at weeks 20-32 included Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI). Safety was ­determined via incidence of treatment-related adverse events (AEs). Results A total of 131 patients were included in the analysis. Mean age was 44.3 ± 17.5 (range: 12-78) years; 53.4% (70/131) were female. UPA doses were 15 mg (43.5%, 57/131) or 30 mg (56.5%, 74/131) once daily. Previous treatments included: topical therapy (100%, 131/131), phototherapy (29%, 38/131), systemic non-biologic therapy (75.6%, 99/131), and systemic biologic/JAKi therapy (38.9%, 51/131). At weeks 20-32: 85.5% (112/131) of patients achieved IGA 0/1; 84.3% (59/70), 75.7% (53/70), and 62.9% (44/70) of patients achieved EASI improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 12.7 to 0.7 (p=0.0001; mean EASI improvement = 88.8%); 94.3% (66/70), 92.9% (65/70), 90% (63/70), and 77.1% (54/70) of patients achieved absolute EASI scores <7, 5, <3, and <1, respectively; mean BSA was reduced from 16.4% to 0.9% (p=0.0001; mean BSA improvement=92.5%); mean IGAxBSA was reduced from 53.5 to 1.6 (p=0.0001; mean IGAxBSA improvement=95.7%); and mean DLQI/CDLQI was reduced from 13 to 1.2 (p=0.0001; mean DLQI/CDLQI improvement=90.5%), with 84.6% (55/65) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 38.9% (51/131) of cases. Common concomitant therapies included topical corticosteroids (56.5%, 74/131), systemic corticosteroids (5.3%, 7/131), and topical calcineurin inhibitors (3.8%, 5/131). Frequent AEs included: acne (18.3%, 24/131), hypertriglyceridemia (18.3%, 24/131), elevated creatine phosphokinase (12.2%, 16/131), herpes simplex (5.3%, 7/131), and transaminitis (5.3%, 7/131). Five patients (3.8%) discontinued UPA due to treatment-related AEs (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]; venous thromboembolism [n=1]; folliculitis [n=1]). No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 67.4 patient-years of safety follow-up. Conclusions Our real-world study shows that UPA is an effective and safe therapy for AD, with high levels of skin clearance and a favorable safety profile between weeks 20-32. These results indicate that UPA may perform better in the real-world versus clinical trial setting, as compared to the Heads Up and Rising Up studies at week 24, specifically for IGA 0/1 and EASI75/EASI90/EASI100 achievement. This may be explained by less severe baseline disease severity in our study. Limitations of this study include its sample size and retrospective nature.

Pregnancy and Infant Outcomes After Prenatal Exposure to Golimumab in Denmark, Finland, and Sweden 2006-2019.

To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.

HIV infection is associated with a less aggressive phenotype of inflammatory bowel disease. A multicenter study of the ENEIDA registry.

The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce. To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection. Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD. A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009). HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI.

Course of Uveitis in Patients with Ankylosing Spondylitis during the Interleukin17 Inhibitors Therapy.

Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57-secukinumab (SEC), 22-netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065-0.107), during IL17-i therapy- 9.2 per 100 pt-years (95% CI 0.06-0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079-0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028-0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019-022), p= 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18-0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18-0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group.

Cross-sectional burden-of-illness study in atopic dermatitis (MEASURE-AD) in Australia and New Zealand reveals impacts on well-being.

To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review.

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

Adalimumab (ADA) in Pediatric Non-infectious Uveitis: An Observational Study.

Pediatric uveitis is a rare but sight-threatening condition. Prompt and adequate treatment is crucial to preserve vision and avoid long-term complications. In cases that are resistant to corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis (anti-TNF) biologic agents are usually added. In this study, we report our experience with adalimumab (ADA) anti-TNF use in this group of patients. This is a retrospective observational study conducted in a tertiary pediatric uveitis clinic, in Manchester Royal Eye Hospital. All patients were pediatric patients (aged 2-18 years old) under follow-up during the period of six months. The patients' data were analyzed according to the diagnosis, age of onset of uveitis, systemic medications used before and concomitantly withADA, duration of uveitis before starting ADA, its effect, and time to notice the therapeutic effect in controlling inflammation. Finally, cases were reviewed for the development of anti-drug antibodies. Forty-two patients were included in the study. Idiopathic uveitis was diagnosed in 47.6% of patients and 40.5% of patients were associated with juvenile idiopathic arthritis (JIA). Most (97.6%) of patients were using topical steroids before starting ADA and 95.2% continued using steroids after established ADA use, but systemic steroid use was reduced from 33.3% to 14.3%. The most common non-biologic DMARD used before ADA was methotrexate (MTX) (90.5%). One-third of the patients started ADA between 6 and 12 months after the diagnosis of uveitis, while this percentage dropped to 9.5% the year after diagnosis. Seventy-eight percent of patients acquired complete clinical control of inflammation on ADA use. Almost 78.6% of patients showed a full response in less than six months. In eight patients who were not controlled or were transiently controlled on ADA, three patients had positive anti-drug antibodies. In one patient, antidrug antibodies were identified after 12 years of ADA use, and in another, after 4 years. Adalimumab is an effective, well-tolerated drug in children with uveitis refractory to non-biologic DMARD therapy. DMARDs were usually used alongside ADA in this cohort and few patients had confirmed ADA antibodies.

COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation.

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel disease

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases). Methods We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis. Results Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p&amp;lt;0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P&amp;lt;0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P&amp;lt;0.001) were associated with a higher risk of CDI. Conclusion The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.

Intensified anti-TNF treatment downregulates the phenotype in ulcerative colitis: a 13-year prospective follow-up study

BackgroundModerate to severe ulcerative colitis (UC) is generally treated with a step-up algorithm from 5-aminosalicylic acid (5-ASA) to biological agents. There is no general recommendation if or when to de-escalate or discontinue biological therapy. In this study, we performed biological therapy with anti-tumor necrosis factor (TNF) treatment to endoscopic remission followed by discontinuation of therapy. This is a 13- year follow-up study performed for this treatment algorithm.AimThis study aimed to assess whether the treatment algorithm outlined above influences the UC phenotype toward a milder form and identify potential biomarkers for altering the disease phenotype.MethodsPatients with moderate to severe UC were enrolled from 2004 to 2015 and followed up until 2023 to evaluate disease outcomes. Patients were categorized into subgroups based on the highest treatment level required to attain remission: non-biological therapy, biological therapy, or colectomy. Mucosal TNF mRNA expression levels were measured using real-time PCR.ResultsOut of the 116 patients from the original cohort, 71 individuals who had previously undergone anti-TNF treatment to endoscopic remission and subsequently discontinued anti-TNF therapy were included in the present study. Disease outcomes were registered until 2023. By the end of the observation period, 62% of participants were in remission without biological treatment. Among the 71 patients, 39% never experienced a relapse, 23% relapsed but successfully attained remission with untargeted treatment, 18% relapsed and subsequently received a new sequence of biological therapy, and 20% had colectomy. Normalized mucosal TNF mRNA expression was identified as a significant predictor for clinical outcomes.ConclusionMost UC patients transitioned to a milder disease phenotype without requiring biological therapy. Treating to normalize mucosal TNF expression emerges as a potential biomarker, predicting the downregulation of disease severity.

From pathogenesis to current treatment of the cutaneous psoriasis - a literature review

Introduction:&#x0D; Psoriasis is a chronic inflammatory autoimmune disease that can be divided into several subtypes based on the areas of the body occupied by the lesions and the severity of the disease. The overall prevalence of psoriasis ranges from 0 to 11,8%. The disease occurs with equal frequency in both sexes. PsO cannot be completely cured, so many patients experience stigma and have diminished self-esteem due to the characteristic appearance of the lesions.&#x0D; &#x0D; Aim of the study:&#x0D; The purpose of the study is to summarize the available knowledge about classification and options for psoriasis treatment. The options in diagnosis and treatment, including the latest methods, were described and summarized.&#x0D; &#x0D; Materials and methods:&#x0D; Literature available in the PubMed database was reviewed using the following keywords: “Psoriasis”, “Nail Psoriasis”, “Psoriasis Vulgaris”, “Psoriasis Treatment”, “New Psoriasis Treatment”, “Psoriasis Classification”, “Biologic Therapy for Psoriasis”, “Systemic Therapy for psoriasis”.&#x0D; &#x0D; Conclusions: &#x0D; Psoriasis is a genetic skin condition mediated by the immune system. The underlying mechanisms entail intricate interactions between the innate and adaptive immune system. There are various indices for assessing the severity of psoriasis, the most commonly used of which is PASI(Psoriasis Area and Severity Index). Retinoids, cyclosporine and methotrexate are the non-biologic therapies most frequently employed for moderate to severe psoriasis treatment, while topical therapy, which includes mainly corticosteroids and vitamin D analogues, is a successful approach for effectively managing mild psoriasis.

Comorbidity Burden and Treatment Patterns of Psoriasis in Vietnam: Real-World Data from the EXPAND Study.

Psoriasis is a multi-faceted, immune-mediated inflammatory disease associated with a wide range of comorbidities. Real-world data on treatment patterns, comorbidities, and economic burden in patients with psoriasis are needed for comprehensive patient care in Vietnam. A retrospective chart review study was conducted using secondary data extracted from patients' medical records of two hospitals in Vietnam, with the aim of identifying adult patients with a confirmed diagnosis of psoriasis. The index date was defined as the date of first diagnosis between 1 January 2020 and 31 October 2021. Sociodemographic factors, disease characteristics, comorbidities, medication usage, drug survival, and medication costs were analyzed. A total of 661 patients were identified (mean ± standard deviation [SD] age 43.5 ± 14.8years). The most prevalent comorbidity was dyslipidemia (49.6% of patients), followed by hypertension (23.4%), and psoriatic arthritis (10.4%). In total, 44% of patients received biologic therapies. Overall, 66.7% and 54.3% of patients receiving biologic and non-biologic therapies, respectively, had ≥ 1 comorbidity. Only 23.2% of patients with psoriasis-related comorbidities stopped therapy with biologics. Biologics had a longer retention time (17.0months) than non-biologics (6.0months) in patients with comorbidities. Patients with comorbidities had significantly higher total annual healthcare costs than those without comorbidities (in US dollars: USD901 vs. USD304; p < 0.001), mainly due to the relatively higher costs associated with the use of biologics. Patients with psoriasis in Vietnam experience a high disease and economic burden due to comorbidities. Evidence from this real-world study supports the need for routine monitoring of and an appropriate treatment course for psoriasis-related comorbidities.

Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study.

The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs. Information on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID. The median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient. The treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

A systematic review and meta-analysis of investigating the mutual impact of COVID-19 and psoriasis: Focusing on COVID-19 course in psoriasis and the opinion on biologics in this setting.

This systematic review and meta-analysis aims to investigate the mutual impact of COVID-19 and psoriasis to inform clinical practice and future research. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis protocol for systematic reviews and searched PubMed, Web of Science, Scopus, and Google Scholar until May 1, 2022. Eligibility criteria included full-text articles in English reporting COVID-19 treatment outcomes in psoriasis patients. Studies on animals, letters to editors, non-English studies, and studies with no access to full articles were excluded. Search results were screened and data were extracted by two groups of reviewers with any discrepancies resolved by the senior author. The risk of bias was assessed using ROBINS-I for nonrandomized studies. The hospitalization rate, Intensive Care Unit(ICU) admission rate, case fatality rate, odds ratios of COVID-19 infection and hospitalization rate in psoriasis patients were extracted and analyzed using random effects analysis to calculate pooled prevalence and odds ratios, as well as to explore heterogeneity. We found 1980 records from four databases and included 20 studies after screening and removing duplicates. These studies evaluated 185,000 psoriasis patients and included eight retrospective cohort studies, one case-control study, three cross-sectional studies, and eight case series studies. The impact of the COVID-19 pandemic on psoriasis treatment and the outcome of COVID-19 infection in psoriasis patients receiving different forms of treatment were evaluated. The pooled data from included studies showed that the incidence rate of COVID-19 infection among psoriasis patients was 0.03% (confidence interval [CI]: 0.01-0.06), with a pooled odds ratio of 1.97 (CI: 0.69-5.60) compared to the general population. The hospitalization rate, ICU admission rate, and case fatality rate for psoriasis patients with COVID-19 were 0.17 (CI: 0.10-0.31), 0.06 (CI: 0.06-0.46), and 0.02 (CI: 0.01-0.04), respectively. Additionally, psoriasis patients receiving systemic nonbiologic therapy had a pooled odds ratio of 2.32 (CI: 1.18-4.57) for hospitalization compared to those using biologic agents. Studies have shown that biologic therapy for psoriasis did not increase the risk of hospitalization due to COVID-19 infection and may have even offered some protection. Treatment adherence was higher in psoriasis patients receiving biologic therapies than those receiving conventional therapies. These findings suggest that psoriasis treatment did not negatively impact COVID-19 infection and that treatment could be continued on a case-by-case basis during the pandemic.

Course of uveitis in patients with ankylosing spondylitis during the interleukin 17 inhibitors therapy

Background. Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (iIL17) on uveitis in AS continue to accumulate. Objective – to evaluate the effect of iIL17 therapy on the course of uveitis in AS. Material and methods. 73 patients (pts) with AS (New York criteria, 1984), who received iIL17 (57 – secukinumab (SEC), 22 – netakimab (NTK)) for at least 1 year were included in the study. The average age of pts at the time of inclusion in the study was 41.93±8.95 years, the average duration of AS was 10.75±6.22 years. There were 40 (56.7%) men and 33 (43.3%) women among the pts. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), inflammatory bowel disease (IBD) in 3 (4.1%); in 6 (8.2%) the disease started before the age of 16; 19 (26%) pts had at least 1 episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during iIL17 using. Result. The incidence rate of uveitis before the start of bDMARDs therapy for all pts was 8.3 per 100 pt-years (95% CI: 0.065–0.107), during iIL17 therapy – 9.2 per 100 pt-years (95% CI: 0.06–0.15; p=0.72). The incidence rate of uveitis among pts used SEC was 10.1 per 100 patient-years (95% CI: 0.079–0.13) before the start of bDMARDs therapy, during SEC using – 9.4 per 100 pt-years (95% CI: 0.05–0.15; p=0.74). The incidence rate of uveitis among pts used NTK was 4.8 per 100 pt-years (95% CI: 0.028–0.08) before the start of bDMARDs therapy, during the NTK using – 7.1 per 100 pt-years (95% CI: 0.019–0,22; p=0.3). For patients with a history of uveitis, the incidence rate of uveitis before the start of therapy with bDMARDs was 22.5 per 100 pt-years (95% CI: 0.18–0.28), during iIL17 therapy – 29.1 per 100 pt-years (95% CI: 0.18–0.43; p=0.29). Occurrences of uveitis were observed in 4 of 57 pts (7%) during the using of SEC, and in 1 of 25 pts (4%) – during the NTK therapy. 1 case of new-onset uveitis was recorded during the using of SEC. Conclusion. There were no significant differences in the incidence rates of uveitis during iIL17 using compared with non-biological therapy. iIL17 have not demonstrated a significant effect on the course of uveitis in AS in the study group.

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis.

Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments. Online databases were searched for RCTs published through October 2021. Eligible studies were head-to-head comparisons between systemic therapies and/or placebo reporting 50%, 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) from baseline in adults with moderate to severe plaque psoriasis. Comparisons included tumor necrosis factor inhibitors, interleukin (IL)-17, IL-23, and IL 12/23 inhibitors, and systemic nonbiologics. A multinomial Bayesian NMA was used to derive estimates of the relative efficacy of deucravacitinib and other systemic therapies. Response probabilities for each treatment and corresponding 95% credible intervals (CrIs) for achieving a PASI response were calculated over short-, mid-, and long-term follow-up (weeks10-16, 24-28, and 44-60). The NMA included 47 RCTs. Deucravacitinib showed the highest PASI75 response rates among nonbiologic systemic therapies across time points. Deucravacitinib PASI75 response rate (95%CrI) over short-term follow-up was 54.1% (46.5-61.6), within the range of first-generation biologics (etanercept, 39.7% [31.6-48.3]; infliximab, 79.0% [74.0-83.5]). At mid-term follow-up, deucravacitinib PASI75 increased to 63.3% (58.0-68.4). At long-term follow-up, deucravacitinib PASI75 was 65.9% (58.0-73.4), comparable to first-generation biologics adalimumab (62.8%; 55.3-69.6) and ustekinumab (68.0%; 64.6-71.5). Patients receiving deucravacitinib were more likely to achieve PASI75 response versus apremilast and methotrexate across all time points. The long-term PASI75 response rate for deucravacitinib was similar to those of adalimumab and ustekinumab. The approval of deucravacitinib offers patients the choice of an oral therapy with long-term efficacy similar to that of some biologics.

Skin Clearance is Associated with Reduced Treatment Failure in Patients with Psoriasis: Real-World Evidence from the CorEvitas Psoriasis Registry.

Complete and near-complete skin clearance have become achievable treatment goals for patients with psoriasis receiving systemic biologic therapies. However, there is limited real-world evidence regarding the impact of the degree of skin clearance on biologic treatment patterns among these patients. This longitudinal cohort study assessed the relationship between degree of skin clearance following initiation of a systemic biologic therapy and treatment failure among patients from the CorEvitas Psoriasis Registry (April 2015-August 2021). Patients had Psoriasis Area and Severity Index (PASI) score > 5 at systemic biologic therapy initiation and ≥ 1 follow-up visit(s) within 15months of initiation. Treatment failure (discontinuation due to poor response/adverse event; addition of non-biologic therapy) and degree of skin clearance (measured by PASI) were assessed following biologic initiation. Proportional hazards regression was used to estimate the association between PASI response level and treatment failure over follow-up. This study included 2701 patient initiations from 2516 unique patients with 3846 total visits over follow-up. Over half of the patient initiations (n = 1412; 52.3%) were among patients with PASI >10. Treatment failure occurred in 1.3% of visits at which PASI100 was achieved, while those achieving PASI90 - < 100 and PASI75 - < 90 had treatment failure rates of 3.4% and 3.5%, respectively. After adjustment for confounders, the risk of treatment failure was two to three times higher in the PASI90- < 100 (hazard ratio [HR] = 2.61; 95% confidence interval [CI] 1.35, 5.02; p = 0.004) and PASI75 < 90 (HR = 2.97; CI 1.58, 5.58; p = 0.001) groups compared to the PASI100 group. The risk of treatment failure was more than 20 times higher in the < PASI75 group versus the PASI100 group (HR = 22.26; CI 13.32, 37.21; p < 0.001). The results suggest that patients are more likely to remain on a systemic biologic therapy if they achieve near-complete or complete skin clearance, supporting the continued need to target skin clearance as a treatment goal in psoriasis. ClinicalTrials.gov identifier, NCT02707341.

Research progress of non-biological artificial liver support system therapy for paitents with liver failure

Liver failure progresses quickly with high mortality. Non-biological artificial liver support system therapy is one of the important treatments for patients with liver failure. The basic techniques of non-biological artificial liver support system therapy include plasma exchange, plasma adsorption and continuous renal replacement therapy. In this paper, the effect and choice of these basic techniques, the treatment timing, the possible patients who may benefit, and the existing problems are summarized and discussed. We hope to provide a reference for the rational use of non-biological artificial liver support system therapy in clinical practice.