Previous Biological Treatment Research Articles

Long-term persistence with secukinumab in patients with moderate-to-severe psoriasis

ObjectiveThe aim of this study was to evaluate the real-world persistence, effectiveness, and safety of secukinumab in adult patients with moderate-to-severe psoriasis in two different hospitals. MethodsRetrospective cohort study that used registries and medical records from 2 different hospitals (February 2015–March 2024). Adults with moderate-to-severe psoriasis who initiated secukinumab treatment were identified and followed-up until March 2024, or disenrollment. Baseline demographic and clinical characteristics studied included sex, age at diagnosis, weight, prior failed treatments, duration of treatment and psoriasis area severity index (PASI) score. Adherence was measured using medication possession ratio (MPR); patients with MPR ≥ 80% were considered adherent. Persistence, effectiveness, safety, and dosage regimen of secukinumab were collected. Kaplan–Meier analysis was used to estimate secukinumab persistence using 1-year intervals. ResultsA total of 88 patients with moderate-to-severe psoriasis were included, of whom 45 (51.1%) had not received prior biological treatment. Baseline PASI score was 15.0 ± 2.9 and patients received 1.4 ± 0.8 prior biological treatments. The most common previous biological treatments included anti-TNFα (60.5%) and ustekinumab (20.9%). 34 (38.6%) patients discontinued secukinumab treatment due to the following reasons.19 (21.5%) due to a lack of effectiveness, 8 (9.2%), due to achieve only a partial response, and 7 (7.9%) due to adverse effects. Secukinumab persistence was 61.5 ± [21.7] months for all patients. When performing a subgroup analysis, non-naïve patients obtained a persistence of 61.5 ± [12.4] months followed by 54.1 ± [14.8] months for naïve patients (p = .804). Secukinumab persistence at 1 year, 2 years, and 3 years was 72.7%, 51.1%, and 39.8%, respectively. ConclusionsSecukinumab demonstrated persistence in more than 70% of patients with moderate to severe psoriasis after the first year of treatment.

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

Tezepelumab: a promising therapy for severe uncontrolled asthma

Asthma is a complex inflammatory airway disease affecting a significant global population, spanning from childhood through adulthood. Despite advances in treatment modalities, a significant subset of patients, approximately 10%, grapple with severe asthma, characterized by increased healthcare utilization and diminished quality of life. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), offers promising therapeutic potential. TSLP is a protein released by a variety of cells, with a predominance of epithelial cells, in reaction to plenty of stimuli, such examples as viruses, aeroallergens, and others. Its action is upstream and pertains to initiating numerous subsequent innate and adaptive immune reactions, contributing to the continuation of asthma pathophysiological processes. Tezepelumab’s unique efficacy spans diverse severe asthma phenotypes, significantly reducing exacerbation rates across eosinophilic and non-eosinophilic subtypes. Its favorable safety profile and clinically meaningful improvements in asthma control, accompanied by reductions in cytokine levels and baseline biomarkers, underscore its broad impact on asthma inflammation. Its efficacy, irrespective of type 2 (T2) endotype, reinforces the idea that TSLP blockade broadly inhibits pathways crucial to asthma pathophysiology, rather than narrowly focusing on individual downstream factors, as previous biological treatments have. This review discusses the rationale for TSLP blockade and the efficacy of tezepelumab in severe asthma using data from key trials.

Progression of Quality of Life in Patients with Plaque Psoriasis Who Achieved Three or More Years of Complete Skin Clearance with Guselkumab Treatment: a Post hoc Analysis of the VOYAGE 1 Clinical Trial.

The interleukin-23p19 subunit inhibitor, guselkumab, has demonstrated improvements in clinical and patient-reported outcome (PRO) measures in patients with moderate-to-severe psoriasis. Understanding the relationship among clinical response, PRO measures and baseline characteristics could help clinicians individualize treatment plans. The objective of this analysis was to examine changes in signs, symptoms and quality-of-life (QoL) PRO measures in patients who maintained complete skin clearance through ≥ 3years in the phase 3 VOYAGE 1 trial. A descriptive post hoc analysis of data from VOYAGE 1 was conducted to compare baseline characteristics of patients who maintained complete skin clearance (Psoriasis Area and Severity Index [PASI] = 0 for ≥ 156 consecutive weeks) versus patients who did not. Mean scores for individual domains of the Dermatology Life Quality Index (DLQI) and Psoriasis Symptom and Sign Diary (PSSD) were evaluated in patients who maintained complete skin clearance, and baseline characteristics of patients who achieved PRO scores of DLQI = 0/1 and PSSD = 0 were compared with those who did not. Of the 329 patients included in this post hoc analysis, 73 (22.2%) maintained PASI = 0 for ≥ 156weeks. This group had a numerically lower proportion of patients at baseline with obesity, depression or previous biologic treatment and a higher proportion who had never smoked. Patients who maintained PASI = 0 generally achieved positive DLQI and PSSD outcomes, though some impact of residual disease was observed, largely related to the DLQI "Symptoms and feelings" sub-scale and PSSD components "Dryness," "Redness" and "Itch." Patients reporting continued disease impact (despite sustaining PASI = 0) had greater disease severity at baseline versus those achieving DLQI = 0/1 and PSSD = 0. Clinical measures alone do not capture the full patient experience. While both QoL and clinical symptoms are responsive to highly effective treatment, a subset of patients with complete clinical response is still impacted by their psoriasis. Further investigation into this population is warranted. ClinicalTrials.gov, NCT02207231.

Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis

BackgroundTreatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement.ObjectiveThis study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response.MethodsA total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively.ResultsThe following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670–0.773) and validation cohort (AUC, 0.715; 95% CI 0.665–0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications.ConclusionsThis study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility.Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256.

Effect of Treatment With Biologic Agents on the Novel Inflammatory Biomarkers Systemic Immune Inflammation Index and Systemic Inflammation Response Index for Psoriasis.

Psoriasis is a chronic cutaneous disorder with underlying systemic inflammation. The systemic immune inflammation (SII) and systemic inflammation response indexes (SIRI) are novel biomarkers that indicate systemic inflammation. We aimed to evaluate the effect of biological agent treatment on SII and SIRI in psoriasis patients. Between April 2019 and October 2022, SII and SIRI were retrospectively evaluated in patients with psoriasis before and three months after the initiation of biological agents. This study included 220 patients, 101 females and 119 males. SIRI was significantly higher in male patients compared to females (P < 0.001). Although not statistically significant, SII and SIRI were higher in obese patients, patients with severe psoriasis, longer disease duration, nail involvement and patients who received previous biological agent treatment. SII was also higher in patients with hypertension, diabetes, hepatic steatosis, depression and coronary artery disease (P = 0.801, P = 0.752, P = 0.706, P = 0.079, P = 0.861, respectively), whereas SIRI was higher in patients with diabetes and depression (P = 0.263, P = 0.777, respectively). Both SII and SIRI statistically significantly decreased after treatment with adalimumab, infliximab, ixekizumab, secukinumab, ustekinumab and risankizumab. SII and SIRI may indicate the severity of psoriasis as well as SII may be associated with psoriatic arthritis, hypertension, hepatic steatosis and coronary artery disease in patients with psoriasis. There is no consensus on the biomarkers that can be used to create an optimized treatment strategy in psoriasis. Therefore, SII and SIRI may be helpful in making the choice of treatment and in the follow-up of patients with psoriasis treated with biological agents.

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study

ABSTRACT Background Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. Research design and methods This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. Results We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. Conclusion This real-world study shows that UST effectively and safely treats patients with UC.

P387 Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn’s disease: multicentric retrospective analysis of 211 patients

Abstract Background Surgical management for patients with inflammatory ileocecal Crohn’s disease (CD) could be a reasonable alternative to second-line medical treatment. Methods A retrospective analysis of patients intervened for primary ileocecal CD with uncomplicated (inflammatory) phenotype at four referral hospitals during 2012-2021 was performed. The objective was to assess short and long-term outcomes of patients operated on for inflammatory, ileocecal CD. Patients operated on due to inflammatory ileocecal CD (last 50 cm of the terminal ileum and cecum), were considered eligible to participate in this study. Operations performed during a 9-year period (2012-2021) were considered for the study. Patients who were operated for CD for advanced structural bowel damage (fibrotic strictures or penetrating phenotype), those who had had previous abdominal CD-related procedures, and patients who had disease activity in other anatomical regions at the time of surgery, were excluded from the study. Results 211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The mean length of stay for patients was 5 days, with only 24 patients (11%) requiring a prolonged hospitalization. The complication rate was 23.7% (50 patients), but most complications were minor (Clavien-Dindo &amp;lt; IIIa), with only 11 patients (5%) presenting with major complications. Leak rate for patients who received a primary anastomosis was 2.9%. The median length of the resected bowel was 25 cm (7-92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17-70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p=0.001) was associated with a higher risk of overall recurrence. Conclusion In this study, surgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates. Further studies need to validate the present results.

P945 Crohn´s disease response to ustekinumab measured by bowel ultrasound

Abstract Background After the STRIDE-II update for patients with Crohn’s disease (CD) one of the new possible adjunct treatment goals was transmural healing, yet its assessment is still not fully cost/risk-benefit proven. A valuable tool to assess this adjunct goal is bowel ultrasound. For this reason, our aim was to evaluate the bowel ultrasonographic response to ustekinumab at one year. Methods Retrospective, observational, single center study was designed. All adult patients with CD who were treated with ustekinumab and had a bowel ultrasound just before the induction dose with ustekinumab and who repeated the bowel ultrasound one year after it were included. Examination was done by ultrasound machine (Hitachi Avius) with low frequency curved-array (1-5 MHz) and high-frequency linear-array (5-13 MHz) transducers. The measured bowel ultrasonographic variables were: wall thickness, Doppler activity (Limberg index) and fatty striation. Ultrasonographic response was defined as a reduction in wall thickness of at least 25%, 2mm or 1mm plus 1 Doppler sign. Remission was defined as wall thickness less than 3mm plus absent Doppler sign. Patient demographics and disease characteristics were also collected: age, sex, extension of CD, previous biologic treatments and ustekinumab trough levels. Demographic and clinical characteristics were compared using χ2 analysis (or Fisher’s exact test), Student’s t test or Spearman correlation. All statistical analyses were performed using the STATA Statistical Software. Results A total of 41 patients (56.1% female) with a mean age of 57.9 years (SD ±2.7) were included. 63.4% had ileal disease and 36.6% ileocolonic involvement. Ustekinumab was first line of biologic treatment in 7.3%, second line in 61.0%, third line in 29.3% and fourth line in 2.4% of patients. 63.4% of patients were on ustekinumab 90mg subcutaneous every 4 weeks at one year with a median trough level of 8.6 (range 7.9-10.6). The median wall thickness measured by bowel ultrasound before induction was 5.5 mm (range 5.0-6.4) and after one year it was 5.0 mm (4.1-5.7) (p=0.47) Figure 1. Before treatment Limberg index was 3 in 26.8% and after treatment it was 3 in 4.9% (p=0.052). Fatty striation was present in 90.2% of patients at the beginning of treatment and in 63.4% at one year (p=0.013). Ultrasound response was achieved in 36.6% of patients while transmural remission was achieved in 12.2% of patients in the first year. No association between ustekinumab trough levels and response/remission were found (p=0.70/p=0.83) Conclusion Treatment with USK was related with an ultrasonographic response in one third of patients with refractory CD at one year. No association between ustekinumab trough levels and ultrasonographic response/remission were found

P184 Challenging Barriers in Inflammatory Bowel Disease: First Observational Analysis of Double Biological Therapy in Mexico

Abstract Background Inflammatory bowel disease is a chronic inflammation of the GI tract, despite advances in treatment with biologic therapy, some patients may develop an inadequate response, known as refractory IBD (rIBD).Given this reality, the approach of double biological therapy (DBT) has emerged to effectively address and improve control of inflammation, providing them with an additional therapeutic option Methods Pilot prospective observational study evaluateing response to DBT in patients with refractory IBD Results A total of 7 patients with rIBD who received DBT were included, the average age was 29 ± 9, all female. The average duration of illness before starting dual therapy was 8 ± 2years. Patients had received an average of 2 previous biological treatments, 4 (57%) had a history of surgery related to IBD, 5 (71%) and 2(29%) had a history of stenosis and fistulas respectively and 100% used steroids and immunomodulators before starting DBT. Four DBT combinations were evaluated: CERTOLIZUMAB+VEDOLIZUMAB (group 1), USTEKINUMAB+VEDOLIZUMAB (group 2), INFLIXIMAB+USTEKINUMAB (group 3) and INFLIXIMAB+VEDOLIZUMAB (group 4).Group 1 included 1 patient with improvement in clinical activity, with a decrease in endoscopic activity from i4 to i2 by Rutgeerts criteria and Nancy index 1.Group 2 included 4 patients showed improvement in clinical and endoscopic activity, there was a reduction in clinical activity by CDAI from 225 to 66, and improvement in endoscopic activity from L1 B2 to L1 B1, i0 L2 B3P to i0 L1 B1 and i3 L3 B2 to i2 L3 B1 with different activity rates, Nancy's histology that varied from 0 to 3.Group 3 included 1 patient showed a reduction in clinical activity by CDAI from 210 to 166, endoscopic activity also decreased from i0 L2B3P to i0 L1 B1 with Nancy index of 2.Group 4 includes 1 with a decrease in clinical activity by Truelove-Witts from 2 to 2, endoscopic activity also decreased from 8 to 5 accordingto UCEIS with Nancy index of 1.In all groups, a reduction in the use of steroids was observed and no cases of infections associated with dual biological therapy were reported Conclusion This prospective observational pilot study represents the first analysis in Mexico and, to our knowledge, in Latin America, on the use of DBT in patients with rIBD who showed clinical, endoscopic and histopathological improvement in the majority of cases. It is important to recognize the limitations of this study, such as its pilot design and sample size. This pioneering study in refractory IBD presents encouraging results that suggest clinical and endoscopic benefits in the treated patients. These results justify the conduct of larger studies to strengthen the evidence and provide a solid basis for thepotential use of this therapy in clinical practice

P494 Efficacy and safety of Upadacitinib in moderate to severe paediatric Crohn’s disease and ulcerative colitis in a tertiary Paediatric IBD (PIBD) centre – A case series

Abstract Background Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis. Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD. We present our experience in this case series of patients ≤ 18 years on Upadacitinib. Methods We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered. Results 12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8-16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38-1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections. Abbreviations CD, Crohn's disease; UC, ulcerative colitis; IBD-U; inflammatory bowel disease unclassified; Upa, upadacitinib; AEs; adverse events Conclusion The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings. Table 1. Patient Characteristics

P764 Darvastrocel in Treatment of 152 Patients with Perianal Crohn's Disease - Observational Study

Abstract Background Complex perianal fistulas significantly affect quality of life and treatment costs in patient with Crohn's disease (CD). Application of adult allogeneic expanded adipose-derived mesenchymal stem cells (Darvastrocel, Takeda Pharmaceuticals) represents novel treatment modality for this challenging condition. The aim of this study was to examine the long-term effects of Darvastrocel (DVS) in patients with complex perianal fistula associated with Crohn’s disease. Methods The study was conducted at two Czech medical facilities (NH Hospital, Horovice and ISCARE, Prague). All consecutive CD patients with complex perianal fistula (up to 2 internal and 3 external openings) treated by the same team with DVS between August 2019 and July 2023 were enrolled into the study and followed prospectively. All fistulas persist despite previous biologic and surgical treatment. The technique of DVS application was based on the ADMIRE CD study protocol and was in accordance with SPC. Fistula tract was curetted, internal opening closed and leak test performed under GA. DVS was applied below the internal opening and along the fistula tract subsequently. Perianal area was then assessed at week 3, month 3 and 6 and then every year postoperatively. Results In total, 152 patients (53.9% male, 46.1% female) with median age of 36.6 (20-72) years were enrolled (tab. 1). Primary success rate detected within the period of 19.8 (4.2-50.2) months after application was 80.3% (122 patients). Fistula recurred in 9 patients (at the site of original fistula in 6 and in a new location in 3 cases), resulting in a sustained healing rate of 74.3% (113 patients) observed within average of 27.2 months. The Perianal Crohn's Disease Index was significantly lower 3, 6, and 12 months after application in the healed compared to failed group - 1 (0-9), 0 (0-8) and 0 (0-9) vs. 7 (1-13, 8 (0-12) and 6 (0-12), p&amp;lt;0.005. Postoperatively, 48 patients (31.6%) were prescribed antibiotics due to inflammatory changes in perianal area. Out of 122 healed patients 31 (25.4%) received antibiotics for 17 (5-37) days, while 17 (56,6%) patients with treatment failure were treated for 16 (7-70) days. Conclusion This real-life study showed that Darvastrocel is highly effective in treatment of complex perianal Crohn’s disease resistant to conservative and surgical management. Moreover, for some patients (anal stricture, chronic changes in anorectum) this may be the only available therapeutic option. Intermittent antibiotic treatment did not affect long-term outcomes. We consider clinical response (crucial for the patient's quality of life) sufficient for predicting sustained long term remission.

P786 Evaluation of the efficacy and safety of the use of subcutaneous infliximab in the treatment of inflammatory bowel disease in naïve patients

Abstract Background The use of intravenous (IV) infliximab in inflammatory bowel disease (IBD) is an established treatment with a demonstrated safety and efficacy profile. Subcutaneous (SC) infliximab is currently available, showing comparable results in disease maintenance, but lacking studies in naïve patients. This study aims to determine whether initial treatment with SC infliximab is as effective and safe in real clinical practice. Methods This is a single-center observational study that included patients with clinically active IBD who directly initiated SC infliximab after IV induction (IV 5 mg/kg 0-2 weeks and SC 120 mg/2 weeks at week 6). The primary objective of the study was to evaluate the response to SC treatment at 3 and 9 months in patients naïve for infliximab. Secondary objectives included the need for intensification, rescue treatments (corticosteroids, change of biologic or surgery), the occurrence of adverse effects and pharmacokinetic aspects (blood levels, development of antibodies to infliximab or ATIs). Clinical activity was assessed using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and Partial Mayo Score (PMS) for ulcerative colitis (UC). In addition, biochemical parameters (hemoglobin, albumin, C-reactive protein, and fecal calprotectin) were monitored. Results A total of 19 patients were included, 14 with CD and 5 with UC (Table 1). Among them, 16/19 had not received previous biological treatment and 3/19 had received another anti-TNF other than infliximab. They were followed at 3 (18/19) and 9 months (18/19) (Figure 1). Significant improvement (p&amp;lt;0.05) was observed in the parameters of clinical activity (6/18 persisting with mild-moderate activity at 9 months) and biochemical activity (fecal calprotectin). Infliximab levels were adequate at 3 (median 12; range 3.2-39) and 9 months (median 15.9; range 0.3-51). In total, 31.6% of patients (6/19) discontinued treatment: 1/19 due to mild acute urticaria at baseline, 2/19 due to the development of ATIs (one also developed lung abscesses requiring hospitalization) and 3/19 due to loss of secondary response requiring a change of biologic. Of the latter, one also needed treatment with oral corticosteroids. In none of the patients was the treatment intensified or surgery required. Conclusion Treatment with SC infliximab in naïve patients seems to be an effective and safe alternative with results comparable to IV infliximab in real clinical practice. In our 9-month study, clinical scores and fecal calprotectin improved significantly, with low immunogenicity rates. Only 31.6% of patients discontinued treatment due to adverse effects or loss of response. Table 1. Baseline characteristics of patients

Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn's disease: Multicentric retrospective analysis of 211 patients

BackgroundSurgical management for patients with inflammatory ileocecal Crohn's disease (CD) could be a reasonable alternative to second-line medical treatment. AimTo assess short and long-term outcomes of patients operated on for inflammatory, ileocecal Crohn's disease. MethodsA retrospective analysis of patients intervened at four referral hospitals during 2012–2021 was performed. Results211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The median length of the resected bowel was 25 cm (7–92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17–70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p = 0.001) was associated with a higher risk of overall recurrence. ConclusionSurgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis. This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting. This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events. Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001). This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

Persistence and effectiveness of guselkumab treatment in patients with moderate-to-severe plaque psoriasis in a non-interventional real-world setting: The SPRING study.

Guselkumab is a monoclonal antibody that blocks the IL-23 pathway with proven efficacy and tolerability in the treatment of moderate-to-severe plaque psoriasis. To assess the persistence, effectiveness and safety of guselkumab in patients with moderate-to-severe psoriasis in real clinical practice in Spain. SPRING was a Phase IV, retrospective and non-interventional study analysing patients with moderate-to-severe plaque psoriasis who had initiated guselkumab under clinical practice conditions at least 12 months before inclusion in the study. The primary endpoint was persistence (non-persistence: discontinuation or interruption ≥90 days). Effectiveness was assessed using the Psoriasis Area Severity Index (PASI) and Investigator Global Assessment (IGA). Dermatology Life Quality Index (DLQI) and safety were also evaluated. A total of 284 patients were included between September 2020 and June 2021. The 1-year probability of persistence was 89.6% (86.1%-93.3%). The 1-year probability of persistence was also calculated according to prior biologic treatment, being 90.3% for biologic-naïve patients and 89.5% for patients who received one or more biologic therapies before guselkumab. Additionally, patients were also classified based on the frequency of the administration of guselkumab treatment; the 1-year probability of persistence was 91.9% in patients receiving guselkumab according to the Summary of Product Characteristics and 89.3% in patients with lengthened intervals of administration. After 1 year, PASI 90 was achieved by 56.4% of patients, IGA 0/1 response and BSA <3% were achieved by 65.5% and 77.8% of patients, respectively, and 65.8% achieved a minimal clinically significant difference (>4-point reduction) in the DLQI score at 1 year. Twenty-six adverse reactions (4 of them serious) were reported in 16 patients. This study suggests that guselkumab has high persistence in real clinical practice in Spain, independently of the previous biologic treatments and changes in the frequency of treatment. Effectiveness and safety are consistent with previously published data.

Early Discontinuation of Apremilast in Patients with Psoriasis and Gastrointestinal Comorbidities: Rates and Associated Risk Factors.

Apremilast, the first oral targeted treatment for moderate to severe psoriasis, is associated with diarrhea, nausea, and vomiting, which have contributed to treatment discontinuation. This study describes early apremilast discontinuation rates in patients with psoriasis, including a cohort with gastrointestinal (GI) comorbidities, and associated characteristics. This retrospective cohort study used IBM® (now Merative™) MarketScan® commercial and Medicare claims data to identify adults with psoriasis who filled their first apremilast prescription between September1, 2014 and March31, 2020. Discontinuation was defined as a gap of > 30days after exhausting the days' supply of a prescription fill. The GI comorbidity cohort included patients with ≥ 1 claim for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or other GI comorbidity during the study period. Discontinuation rates were high, regardless of previous biologic treatment or GI comorbidities. Among all patients, 25.5% discontinued within 60days and 56.4% discontinued within 180days. Patients who discontinued were more likely to be younger, female, and have IBD, Crohn's disease, or a mental health disorder. At 180days, patients who used biologics previously were more likely to discontinue than biologic-naive patients. Patients with IBD discontinued at a greater rate than those without IBD at 60days (30.3% vs 24.4%; P = 0.018) and 180days (63.6% vs 57.2%; P = 0.026). Differences in discontinuation rates were minimal between GI comorbidity groups; patients with IBS discontinued at numerically higher rates than those without IBS. High rates of early discontinuation were observed for patients with and without GI comorbidities. Early discontinuation, whether attributable to poor tolerability or effectiveness, suggests the need for additional oral treatment options.

Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation.

Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles. The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition. The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥ 18 years and had moderate to severe plaque psoriasis. The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index(PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings.

Quality of Life Benefit and Clinical Predictors of Complete Skin Clearance in Psoriasis: A Multicenter, Prospective, Real-World Study

Background: Newer biologics, such as interleukin (IL)-17 inhibitors, make it possible to achieve complete skin clearance (CSC) in patients with moderate-to-severe psoriasis. However, the clinical meaningfulness and predictive factors of CSC in daily practice have not yet been fully investigated. Objective: The study was conducted to, first, assess the impact of CSC on quality of life (QoL) improvements compared with treatment responses without clearance and, second, identify clinical parameters as predictors of CSC response in psoriasis patients treated with ixekizumab. Methods: Patients attending 26 dermatology centers across China were recruited into this real-world setting between August 2020 and May 2022. Prospective cohort study in which response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI). The absolute DLQI score and DLQI (0) response at week 12 were compared between groups achieving various levels of skin clearance. A stepwise logistic regression analysis was applied to identify which baseline clinical characteristics were predictive factors for CSC. Results: After 12 weeks of treatment, 226 of 511 (44.2%) patients achieved CSC, defined as 100% improvement in PASI score (PASI-100). A significantly higher proportion of patients with CSC versus almost clear skin (PASI 90-99) achieved DLQI score of 0, corresponding to the experience of no impairment on QoL (54.4% vs. 37.7%, p = 0.001). Females patients were more likely than males to achieve CSC response (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.24–2.70), while previous biologic treatment (OR = 0.43; 95% CI: 0.24–0.81) and joint affected (OR = 0.61; 95% CI: 0.42–0.89) were significantly associated with less CSC response. Conclusions: This study highlights the fact that clinical parameters are important in determining CSC response in psoriasis. In daily practice, achieving CSC represents a clinically meaningful treatment goal, especially from the patient perspective.