Use Of Biologic Therapies Research Articles

Past, Present and Future Treatment of Alopecia Areata

Alopecia Areata (AA) is a complex autoimmune condition causing hair loss. In this article, we review the range of published conventional and unconventional treatments. While we explored the effectiveness of commonly used treatments such as topical and intralesional corticosteroids, we have focused on more advanced treatment methods such as the use of phototherapy and biological therapy. Furthermore, we explored published work for the role of unconventional treatments such as garlic, herbal lotions, essential oils and onion juice on AA. While various treatment options exist for AA, their effectiveness and long-term benefits require further research. Biological therapies, particularly JAK inhibitors, offer the most promising possibilities for well-tolerated and effective treatment. More studies are needed to optimize treatment strategies and personalize care based on individual needs and disease severity. Sources were gathered from the Cochrane database and PubMed using the following keywords: alopecia, alopecia areata, hair loss, treatments, systematic reviews and clinical trials

Biologic Therapies across Nasal Polyp Subtypes.

Chronic rhinosinusitis with nasal polyposis is a common inflammatory condition, with subtypes like aspirin-exacerbated respiratory disease, allergic fungal rhinosinusitis, and central compartment atopic disease sharing a common type 2 inflammatory pathway. Respiratory biologic therapies have been developed that target type 2 inflammation. In this article, we discuss the use of respiratory biologic therapies for nasal polyposis in general, as well as within the various subtypes of nasal polyps. Further, we discuss future roles of novel biologic therapies targeting type 2 inflammation in nasal polyposis.

Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the "Silent Zone" to Achieving "Quiet Asthma".

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed "Quiet Asthma".

Blood eosinophilia in patients with severe bronchial asthma and chronic polypous rhinosinusitis treated with dupilumab: A review

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

Management of patients with chronic rhinosinusitis with nasal polyps (CRSwNP): Results from a survey among allergists and clinical immunologists of the North-west and Center Italy Inter-Regional Sections of SIAAIC and otorhinolaryngologists of National IAR

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with chronic inflammation of the paranasal sinuses. In Italy, CRSwNP is managed by allergists/immunologists (AIs) and otorhinolaryngologists (ENTs). Two inter-Regional Sections of SIAAIC (Società Italiana di Allergologia, Asma ed Immunologia Clinica) and the National IAR (Italian Academy of Rhinology), interviewed their respective specialists involved in the management of CRSwNP about screening protocols, comorbidity evaluation, therapeutic management, and outcomes to assess possible differences between these two groups of specialists.The survey “CRSwNP Management: the point of view of the Otorhinolaryngologist and the Allergist-Immunologist” composed of 23 questions, was conducted in 2022 through two inter-regional SIAAIC (North-west and Center Italy) sections and National IAR newsletters.111 AIs and 83 ENTs participated. Both specialists agree on some points, such as the need to ascertain nasal comorbidity in asthmatic subjects, usefulness of combining more than a single parameter to assess disease severity in affected patients, need for a multidisciplinary approach and collaboration with general practitioners. The two groups of specialists give different opinions on a few points, such as the use of oral corticosteroids and investigation for their possible side effects, timing of use of biological therapy, and the goals after its introduction.

Adalimumab in the management of psoriasis and psoriatic arthritis: Results from a Delphi investigation.

Psoriasis (PsO) and psoriatic arthritis (PsA) are often undertreated and require a multidisciplinary approach. In recent years, patent expiration has allowed the introduction of tumor necrosis factor inhibitor (anti-TNF) biosimilars, which have stimulated a significant increase in the use of biological therapies. This article reports the findings of a multidisciplinary approach to achieve a consensus on the use of adalimumab in patients with PsO or PsA. A voting panel of 36 Italian dermatologists and rheumatologists were chosen by eight Italian clinicians (the Board), to provide a consensus on the real-world management of PsO and PsA with adalimumab using the Delphi Method, comprising three survey rounds. Twelve statements were defined by the Board and submitted to the panel (rating scale 1-7). Clinicians reached a wide consensus on the effectiveness (score 6-7: 67%) and long-term efficacy (6-7: 100%) of adalimumab in all clinical forms of PsO and PsA, including pediatric patients (6-7: 85%). Considering cost-effectiveness and safety, adalimumab is suggested as a first-line treatment in patients with enthesitis, predominant peripheral arthritis, axial involvement or associated inflammatory bowel disease (IBD) or uveitis. Adalimumab can be also considered after failure of etanercept (6-7: 94%). Results from this Delphi study clearly show an overall consensus on the use of adalimumab in the management of PsO and PsA, particularly as first-choice for specific subpopulations (uveitis, IBD, hidradenitis suppurativa). Considering the cost-effectiveness of biosimilars within Italy, adalimumab may represent an effective and safe first-line treatment for patients with moderate-to-severe PsO or PsA, and a valid choice for switching after failure.

Patient Perspectives of Bowel Urgency and Bowel Urgency-Related Accidents in Ulcerative Colitis and Crohn's Disease.

Bowel urgency is bothersome in patients with ulcerative colitis (UC) or Crohn's disease (CD) and impacts their well-being but remains underappreciated in clinical trials and during patient-healthcare provider interactions. This study explored the experiences of bowel urgency and bowel urgency-related accidents to identify the concepts most relevant and important to patients. Adults with a diagnosis of moderate-to-severe UC or CD for ≥6 months and experience of bowel urgency in the past 6 months were included. Qualitative, semi-structured interviews were conducted via telephonic/Web-enabled teleconference. Interview transcripts were coded and analyzed in ATLAS.ti 9 using a systematic thematic analysis. In total, 30 participants with UC or CD (n = 15 each) (mean age 52 and 50 years, respectively) participated in the interviews. The majority of participants were receiving biologic and/or conventional therapy (80% and 87%, respectively). Most participants with UC (87%) and all with CD experienced bowel urgency-related accidents. The most frequently reported symptoms co-occurring with bowel urgency were abdominal pain, fatigue, and abdominal cramping. Abdominal pain and abdominal cramping were the most bothersome co-occurring symptoms of bowel urgency and bowel urgency-related accidents. In both groups, participants reported decreased frequency of bowel urgency and not wanting to experience bowel urgency-related accidents at all as a meaningful improvement. Participants with UC or CD expressed bowel urgency and bowel urgency-related accidents to be bothersome and impactful on their daily lives despite use of biologic and/or conventional therapy. These findings underscore the need for development of patient-reported outcome measures to assess bowel urgency in clinical settings.

Use of dual biologic therapy targeting the Th2 and Th17 axes simultaneously to treat patients with atopic dermatitis and concomitant psoriasis, psoriatic arthritis, or inflammatory bowel disease

Use of dual biologic therapy targeting the Th2 and Th17 axes simultaneously to treat patients with atopic dermatitis and concomitant psoriasis, psoriatic arthritis, or inflammatory bowel disease

Efficacy of Biologics in the Treatment of Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

This is the first systematic review and meta-analysis that aims to address the scarcity of research on the use of biological therapy in primary sclerosing cholangitis-inflammatory bowel disease (PSC-IBD) and the historical inadequacy of therapeutic options. Its purpose is to investigate this matter comprehensively and furnish guidance for clinical practice. Utilizing Embase, PubMed, Medline, and clinicaltrials.gov studies investigating the roles of biologics and antibiotics in PSC-IBD were identified. The systematic literature review encompassed articles published from inception through September 2023. Two independent reviewers assessed the articles, and methodological quality was gauged using Review Manager 5.4.2. Nine studies were included in the systematic review and meta-analysis. However, only four met the criteria for inclusion in the meta-analysis due to variability and availability of data; the remaining studies underwent descriptive analysis. Notably, infliximab, adalimumab, vedolizumab, and tofacitinib showed ineffectiveness in reducing cholestatic markers. This review underscores the limited impact of biological and small-molecule therapies on disease progression in PSC-IBD patients, signifying the need for further exploration and development of treatment modalities in this domain.

Safety and efficacy of biologic immunosuppressive treatment in juvenile idiopathic arthritis associated with inborn errors of immunity.

This study aims to describe clinical features, therapeutic outcomes, and safety profiles in patients affected by juvenile idiopathic arthritis (JIA) and inborn errors of immunity (IEI) treated with biological Disease-modifying antirheumatic drugs (DMARDs). We enrolled three patients who were followed in the Pediatric Rheumatology Unit at Meyer Children's Hospital in Florence; these patients were affected by JIA, according to ILAR criteria, and IEI, according to the IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Among them, two patients had 22q11.2 deletion syndrome (22q11.2DS) and one patient had X-linked agammaglobulinemia (XLA). Case 1: A 6-year and 2-month-old boy was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 2 years. He was treated with non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate, along with oral glucocorticoids but with no benefits. Treatment with etanercept allowed him to achieve remission after 10 months. Case 2: A 6-year and 2-month-old girl was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 3 years and 11 months. She was treated with NSAIDs, joint injections, and methotrexate but without clinical response. Treatment with Adalimumab allowed her to achieve remission after 6 months. Case 3: A 12-year and 2-month-old boy was affected by XLA, associated with polyarticular JIA, at the age of 9 years and 11 months. He was treated with NSAIDs, methotrexate, joint injections, and oral glucocorticoids with no benefits. He failed to respond to anti-TNF-alpha, tocilizumab, and abatacept. Currently, he is undergoing therapy with sirolimus plus abatacept, which allowed him to achieve remission after 4 months. Results suggest that the use of immunosuppressive biological therapies can control disease activity in these patients. No adverse drug-related reactions were observed during the follow-up.

The use of biologic therapy in patients with ankylosing spondylitis and coxitis: dynamics of clinical and laboratory parameters and structural progression

Hip joint inflammation (coxitis) occurs in almost half of patients with ankylosing spondylitis (AS) and often leads to early disability. A therapy for this condition has not yet been developed, although it is one of the indications for the initiation of biologic therapy in national recommendations. The review presents data from recent clinical trials on the use of biologics, focusing on the Russian national multicenter study of GO-COX in patients with AS with coxitis.Tumour necrosis factor-α inhibitors have been shown to be effective against inflammatory affection of the hip joint in patients with AS, and their administration over a two-year period inhibits the progression of coxitis.

Major cardiovascular events under biologic psoriasis therapies: a 19-year real-world analysis of FAERS data.

Over the years when biologic psoriasis therapies (TNF inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, and IL-17 inhibitors) have been used in psoriasis patients, reports of major cardiovascular events (MACEs) have emerged. This study aims to investigate the association between MACEs and biologic psoriasis therapies by using information reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS data (January 2004 to December 2022) were reviewed. For each drug-event pair, the proportional reporting ratio (PRR) and the multi-item gamma Poisson shrinker (MGPS) algorithms were used to identify drug-adverse event associations. We filtered the query for indication and identified 173,330 reports with psoriasis indication in FAERS throughout the analyzed time frame. MACEs occurred in 4,206 patients treated with biologics. All the four biological classes had an elevated and similar reporting rates for MACEs relative to other alternative psoriasis treatments (PRR from 2.10 to 4.26; EB05 from 1.15 to 2.45). The descending order of association was IL-12/23 inhibitors>IL-17 inhibitors>IL-23 inhibitors>TNF inhibitors. The signal strength for myocardial infarction (PRR, 2.86; χ2, 296.27; EBGM 05, 1.13) was stronger than that for stroke, cardiac fatality, and death. All the biological classes demonstrated a little higher EBGM 05 score≥1 for the MACEs in patients aged 45-64 years. The time-to-onset of MACEs was calculated with a median of 228 days. Analysis of adverse event reports in the FAERS reflects the potential risk of MACEs associated with the real-world use of biological therapies in comparison to other alternative psoriasis treatments. Future long-term and well-designed studies are needed to further our knowledge regarding the cardiovascular safety profile of these agents.

498 - Real-world use and effectiveness of upadacitinib in adults and adolescents with atopic dermatitis: preliminary analysis of the real-world multicountry AD-VISE study

Abstract Introduction &amp; Objectives Upadacitinib (UPA) 15 and 30 mg once daily is approved for moderate to severe atopic dermatitis (AD) in several jurisdictions, including the European Union, Japan, Canada, and the United States, with indication/posology differences. Clinical studies have documented the safety and efficacy of UPA; however, real-world data on UPA are limited. The AD-VISE study objective is to characterize the real-world utilization patterns and effectiveness of UPA 15 and 30 mg in adults and adolescents with AD in clinical practice. Materials &amp; Methods AD-VISE is an ongoing observational, prospective, multicountry study to assess the use of UPA in routine clinical practice for 2 years. Adult and adolescent patients (pts) receiving UPA for AD are being enrolled. Primary effectiveness outcome measures included validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0/1 at month 4. Other outcome measures included Eczema Area and Severity Index (EASI), Worst Pruritus Numeric Rating Scale (WP-NRS), and Dermatology Life Quality Index (DLQI). This interim analysis (data cutoff February 27, 2023) reports baseline data and 2- and 4-month effectiveness data. Effectiveness analyses included pts that were enrolled at least 4 months by the data cutoff date or discontinued from the study; non-responder imputation with multiple imputation (NRI-MI) was used. Results Baseline analyses included 267 pts, of whom 21 (7.9%) were adolescents; effectiveness analyses included 209 patients (NRI-MI). Overall, 155 (58.1%) pts started on UPA 15 mg and 112 (41.9%) started on UPA 30 mg. Most pts in this analysis were from Canada (56.2%), followed by Russia (10.9%) and Australia (8.6%). Mean (SD) UPA exposure was 218.8 (±117.6) days; 5.6% of pts discontinued UPA and 3.7% discontinued the study. The most common reason for starting on UPA 15 mg was attempting lowest possible effective dose (42.9%) and on 30 mg, high disease burden/severity of skin symptoms (35.2%). More pts starting UPA 30 mg vs 15 mg were between 18 to &amp;lt;65 years old (96.4% vs 76.1%), male (61.6% vs 51.0%), had severe AD (vIGA-AD score 4: 53.6% vs 46.3%), had prurigo nodules (30.6% vs 18.4%), asthma (45.5% vs 24.5%), and prior biologic systemic therapy use (16.1% vs 10.3%) . More than half of the pts (51.2%) achieved vIGA-AD 0/1 at month 2, and this proportion increased to 61.3% at month 4. Similarly, rate of achieving EASI 90 (month 2: 46.9%; month 4: 57.2%) and DLQI 0/1 (month 2: 35.1%; month 4: 41.3%) increased, whereas rates were maintained for ≥4-point WP-NRS improvement (month 2: 68.1%; month 4: 69.3%). Similar results were observed with other endpoints. Conclusion Initial findings from the AD-VISE study, the largest study to report multicountry real-world data on UPA treatment patterns and effectiveness in AD, suggest that most pts achieved clear/almost clear skin and clinically meaningful itch improvement by month 4. Because this is a real-world observational study, it was expected that physicians start with UPA dose per local label. The main reason for starting UPA 30 mg was high disease burden/severity of skin symptoms, whereas 15 mg was started to attempt the lowest possible effective dose. More pts starting UPA 30 mg vs 15 mg were adults, male, and had prior biologic systemic therapy use.

Modern practical management of acute severe colitis.

Acute severe ulcerative colitis (ASUC) is one of life-threatening complications that occur in one-fifth of ulcerative colitis (UC) patients with significant morbidity and an estimated mortality rate up to 1%. There are no validated clinical scoring systems for ASUC. Intravenous corticosteroids remain the cornerstone for the management of ASUC patients However, one-third of patients are steroid refractory and require colectomy in the pre-biologic era or salvage therapy in the post-biologic era. The currently available predictors of non-response to steroids and salvages therapy are sub-optimal. Furthermore, there is a need for the development of clear outcome measures for ASUC patients. Although infliximab and cyclosporin are both effective as salvage therapy, they still carry a rate of treatment failure. Hence, there is an unmet need to explore alternative therapeutic options before colectomy particularly in prior infliximab-exposed patients. This may include the introduction of small molecules with rapid onset of action as a salvage or sequential therapy and the use of slow-onset other biological therapy after "bridging" with cyclosporine. In this article, we explore the current best evidence-based practice and detail the gaps in knowledge in the management of ASUC.

PREVALENCE OF FRAILTY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. A PILOT STUDY

Abstract Frailty is a multidimensional syndrome that leads to greater vulnerability to stress, increasing the risk of adverse health outcomes. It is a dynamic process, with transitions between being robust, pre-fragile and fragile over time, suggesting that it is modifiable. Inflammatory bowel disease (IBD) results in altered immune function with amplified inflammation. When severe, it manifests with features associated with frailty, such as weight loss, fatigue, and sarcopenia. The first studies on frailty in IBD were carried out in a surgical context. Subsequent studies have associated frailty with increased risk of mortality as an independent factor in IBD patients. Of the available evidence, all are retrospective -except one- and the majority measures frailty with associated ICD-10 diagnoses, which can underestimate its prevalence in younger patients. There is no consensus in the literature on the best tool to measure frailty, however, this pilot study will objectively evaluate, using a risk score, the prevalence of this syndrome, which will allow, in the future, to carry out prospective studies that characterize frailty in IBD, understand the dynamic and longitudinal relationship between frailty and disease activity and, if appropriate, design and test interventions to alleviate this syndrome and its consequences in this population. This was a descriptive study, with the objective to determine the prevalence of frailty in IBD patients in a teaching hospital in Chile. We also compared the characteristics of frail vs non-frail IBD patients. Frailty was measured using SHARE-FI tool, which is a validated score to measure frailty in primary care, even in patients under 65 years of age. 64 patients were recruited, 28 had ulcerative colitis, 33 had Crohn’s disease and 3 had indeterminate colitis. 62.5% were female, with an average age of 42,3 ± 13,65 years. Average years since diagnosis were 11,6 ± 9,89. The prevalence of frailty was 40,62%. No association was observed between the presence of frailty and the type of IBD, IBD activity indices, use of corticosteroids, use of biologic therapy, surgeries associated with IBD, IBD flare-ups with hospitalization within the last year, calprotectin levels, vitamin D levels. The odds of the presence of frailty in women are 4,2 times greater than in men, being women a possible risk factor for frailty. The frailty group had worse quality life measured with the IBD Questionnaire 9 (OR 0,86 [IC95% 0,79-0,94). In conclusion, the prevalence of frailty in IBD was 40,62%. Contrary to what might be assumed, frailty turned out to be a condition independent of the type of IBD, time of evolution, activity and treatment, mostly associated with female sex and a worse quality of life. New studies are required to determine factors predisposing to frailty in IBD patients and prevent its appearance in order to improve their prognosis.

RETROSPECTIVE, SINGLE-CENTER, REAL-WORLD ANALYSIS OF BIOLOGIC AND IMMUNOMODULATOR THERAPY DISCONTINUATION IN ELDERLY IBD PATIENTS

Abstract BACKGROUND The population of elderly inflammatory bowel disease (IBD) patients is increasing each year, however use of immunomodulators and biologic therapy in this population remains low. Clinical IBD drug trials limit enrollment of elderly patients. This leads to poor understanding of medication adverse effects and long-term outcomes in this population. Medication sustainability reflects drug efficacy and safety of drugs, which lead to better adherence. The primary aim of this study was to compare the discontinuation rates of various IBD therapies in a cohort of elderly patients and provide some guidance on positioning therapies within this population. METHODS This was a single-center retrospective study conducted at an academic institution. Elderly IBD patients 60 years or older followed between 2016-2022 were included in the study. Patients had to be on either immunomodulator and/or biologic therapy. Chart review was performed to extract demographic data, duration of IBD therapy, and reasons for discontinuation. A Kaplan-Meier survival curve was generated per IBD therapy to depict drug sustainability stratified by reason for discontinuation. Statistical analysis was performed to assess for significant differences across survival curves. RESULTS A total of 224 elderly IBD patients were included in the study analysis. The cohort was comprised of 97 (43.3%) patients with ulcerative colitis (UC) and 127 (56.7%) patients with Crohn’s disease (CD). For both CD and UC, there were no significant differences in biologic drug discontinuation rates due to inadequate disease control (p=0.26 for CD; p=0.74 for UC). There was a significantly increased risk of elderly IBD patients stopping anti-TNF therapy due to medication adverse event compared to those on anti-integrin therapy (p=0.002) and immunomodulator therapy (p=0.003). CONCLUSIONS While the number of biologics used to treat IBD has increased in the last few decades, there is a paucity of studies examining real world sustainability of biologics particularly in elderly patients. With regards to effectiveness, our study showed that there was no significant difference among the three classes of biologics being discontinued due to poorly controlled disease. However, results of our study suggest that anti-TNF therapy is less sustainable in elderly IBD patients compared to other biologics and immunomodulator therapy due to patient experienced adverse events. Our results are pertinent to clinical practice as prescribing biologics other than anti-TNF therapy may increase an elderly patient’s therapy longevity and lead to optimized clinical outcomes. Figure 1 shows time to biologic discontinuation due uncontrolled disease by IBD subtype. For both Crohn’s disease and ulcerative colitis, there was no significant difference in drug survival per biologic with regards to discontinuation due to inadequately controlled disease. Figure 2 shows time to therapy discontinuation due to patient experienced adverse events. This included infections, infusion reactions, systemic reactions, laboratory abnormalities, financial burden, and non-compliance. There was a significantly increased risk of elderly IBD patients stopping anti-TNF over time due to adverse events compared to those on anti-integrin and immunomodulator therapy.

P1108 Factors Associated with Delayed Diagnosis of Inflammatory Bowel Disease and Risk of Complications: Analysis of the Brazilian National Registry

Abstract Background The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) has established a national registry of inflammatory bowel disease (IBD). Timely diagnosis and treatment of the disease are crucial to mitigate the risk of complications in this patient population. Therefore, this study aimed to assess the variables associated with delayed diagnosis and the frequency of complications in IBD patients in Brazil. Methods A cohort study was conducted from August 2020 to August 2023. Data were obtained from medical records and patient consultations using the REDCap platform, with approvals from the ethics boards of participating institutions. Patients were categorized based on the time from symptom onset to diagnosis: &amp;lt; 1 year, 1 to 1 year 11 months, and ≥ 2 years. Socioeconomic and clinical data, such as disease extension, use of biological therapy, and complications like the need for surgery or hospitalization, were evaluated. Results The study included 2,436 patients, with 1,147 diagnosed with ulcerative colitis (UC) and 1,289 with Crohn's disease (CD). Of these, 62% were managed in public centers, and 38% in the private system. The age at diagnosis was 38 ± 15.5 years for UC and 33.7 ± 14.9 years for CD, with females predominating (64.5% for UC and 53.4% for CD). Among UC patients, disease extension included pancolitis (43.5%), left colitis (28.8%), and proctitis (27.7%). The time between symptom onset and diagnosis was longer in CD patients (p&amp;lt;0.001), as follows: &amp;lt; 1 year (UC 58.4% and CD 50.9%), 1 to 1 year 11 months (UC 22.3% and CD 21.1%), and ≥ 2 years (UC 19.3% and CD 28%). The shortest interval in UC patients was observed in private services (p&amp;lt;0.001), Southern and Northeastern regions of Brazil (p&amp;lt;0.001), and in patients without extraintestinal manifestations (EIM) (p=0.003). No differences were noted regarding disease extent, need for surgery, hospitalization, presence of cancer, or use of biological therapy. In CD patients, the shortest interval was observed in private services (p&amp;lt;0.001), the Southern region of Brazil (p&amp;lt;0.001), and was associated with a lower rate of hospitalization due to complications or disease activity (p=0.032). Among those who underwent surgery (35.6%), patients operated on in a public university hospital experienced a greater delay in diagnosis (p=0.014). No differences were observed regarding the presence of perianal disease, need for surgery, cancer, or use of biological therapy. Conclusion The window of opportunity is imperative to reduce complications, especially in CD. Further epidemiological studies are needed to shape national public health policies, emphasizing early diagnosis and appropriate treatment of IBD.

P836 Prospective evaluation of the switch from adalimumab originator to different biosimilars in IBD patients : acceptability and persistance at 1 year

Abstract Background The use of biological therapies represents a major source of direct healthcare costs for inflammatory bowel disease (IBD) in industrialised countries. Several adalimumab (ADA) biosimilars are available for Crohn's disease (CD) and ulcerative colitis (UC) patients. The aims of our study were to assess the acceptance of switching from Humira® to different ADA biosimilars in IBD patients, the biosimilar persistence at 1 year, and the acceptability of the switch. Methods From July 2020 to September 2021, we proposed for consecutive and ambulatory IBD patients on maintenance Humira® to switch to one of the five ADA biosimilars available at the time of the study (Amgevita®, Idacio®, Imraldi®, Hulio®, Hyrimoz®) at Lille University Hospital (France). Patients accepting the switch chose a ADA biosimilar with an IBD nurse and were followed prospectively for 1 year. Biosimilar persistence was assessed at 6 and 12 months using the Kaplan-Meier method. Factors associated with switch acceptance and biosimilar persistence were identified by logistic regression tests (Chi-2). Data on efficacy, safety and rate of return to ADA originator were assessed at 6 and 12 months. At 12 months, acceptability of the switch was assessed by a questionnaire. Results 97 patients (84 CD patients; 13 UC patients) were included in the study. 89/97 patients (91.8%, including 76 CD patients) accepted the switch from ADA originator to a biosimilar. Poor opinion of generic drugs was the only factor associated with refusal to switch. At 12 months, 61 patients (71%) were still on ADA biosimilar and 54 patients (60%) were still treated with the biosimilar initially introduced. During the follow-up, the proportion of patients treated with Hulio® remained stable (around 30%), while the proportion of patients treated with Amgevita®, Idacio®, Imraldi® and Hyrimoz® decreased (from 33.7% to 22.5%, from 20.2% to 5.6%, from 8% to 4.5% and from 10.1% to 5.6%, respectively) (Figure 1). One quarter of patients switched back to ADA originator at 12 months. Thirty-seven patients discontinued the treatment. Among them, 22 patients (59.5%) discontinued due to injection site reactions. Clinical remission rates were stable between the baseline and the 6 and 12 months evaluation (94.4%, 88.8% and 89.2% respectively). The switch from ADA originator to a biosimilar was considered acceptable for 31/38 patients (81.6%) evaluated at 12 months. Conclusion A large proportion of IBD patients (91.8%) accepted the switch from ADA originator to a biosimilar and 60% continued ADA biosimilar at 1 year. The high acceptability of the switch encourages the use of ADA biosimilars in clinical practice.

P581 Age-related patterns in biological therapy use and surgery among patients with IBD: Insights from the Belgian PANTHER cohort

Abstract Background Inflammatory bowel diseases (IBD) are predominantly diagnosed during the second to third life decade. However, the disease may manifest itself at any age and current understanding of differences in clinical presentation and therapy use among age groups is still limited. We aimed to analyse age-related patterns in biological and surgical treatment among patients with IBD. Methods This study utilized data from the PANTHER cohort, a prospective Belgian inception cohort including 473 adult patients with IBD from 3 Belgian referral centres. Patient inclusion took place from 2015 to 2023. Patients were categorized into groups based on the age at diagnosis: 'young adult-onset' (18-39 years), 'adult-onset' (40-59 years), and ‘elderly-onset’ (³60 years). Baseline characteristics and treatments were analysed using Chi square, Mann-Whitney U tests, log-rank tests and/or Cox regression in SPSS. Results Baseline characteristics are shown in Table 1. No significant differences were found between age groups in terms of IBD diagnosis, gender, median follow-up duration, and smoking status. Use of biologics differed significantly across age groups with highest uptake in young-adult onset patients (65.8%, P&amp;lt;0.001). Significant differences were found in selection of first biologic with vedolizumab as most frequently selected option in the elderly compared to anti-TNF in the youngest age group (P=0.002). Time to initiation of a biological was earlier in the youngest cohort (P=0.002, Figure 1). Cox regression analysis revealed that older age at diagnosis (HR 0.987, 95%CI [0.98;0.996], P=0.006), UC (HR 0.495, 95%CI [0.50;0.39], P&amp;lt;0.001) and centre of follow-up (Brussels vs Leuven: HR 0.663, 95%CI [0.4;1], P=0.048) were associated with a lower risk of biological initiation. When analysing CD separately, independent risk factors associated with biological use were perianal disease (HR 2.26, 95%CI [1.6;3.2], P&amp;lt;0.001), L3 (HR 1.85, 95%CI [1.3;2.6], P&amp;lt;0.001,) and L4 (HR 12.7, 95%CI [1.6;98.7], P=0.015,) location (compared to L1 location). In UC patients, E2 (HR 7.9, 95%CI [2.8;22.4], P&amp;lt;0.001) and E3 (HR 6.9, 95%CI [2.4;19.3], P&amp;lt;0.001) were related to earlier use of biologics. During follow-up, 19% of CD and 5.1% of UC patients required IBD-related surgery. Univariate analysis showed a higher need for surgery in younger patients (P=0.042), however, this difference was no longer significant when analysing CD (P=0.272) and UC (P=0.09) patients as separate groups. Conclusion Analysis of the PANTHER Biobank reveals significant age-related variation in the administration of biological therapies among IBD patients.