Previous Treatment Failure Research Articles

Avatrombopag in immune thrombocytopenia: A real-world study of the Spanish ITP Group (GEPTI).

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

ATH434, a promising iron-targeting compound for treating iron regulation disorders.

Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10-31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd's of 1-4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46-9.59µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.

Real-World Effectiveness and Use of Dupilumab in Eosinophilic Esophagitis.

Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness. We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response. Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy. Endoscopic assessment was lacking in 25.9%, but those with follow-up showed high histologic remission (92.3% first-line and 85% previous treatment failure). Dupilumab demonstrates effectiveness across EoE severity, including milder disease without previous treatment failure. Improving follow-up and assessing cost-effectiveness will help clarify its role in the treatment algorithm.

Repeat uterine artery embolization for uterine leiomyomas: Indications, strategies, and outcomes – A case report

Uterine leiomyoma is a frequent cause of abnormal uterine bleeding, especially among African Americans. It is also associated with dysmenorrhea, pelvic pain, infertility, and complicated pregnancies. While hysterectomy and myomectomy are more common forms of treatment for uterine leiomyoma in the United States, uterine artery embolization (UAE) offers a uterus-preserving alternative, with lower rates of major complications, although with an increased risk of reintervention. This case study presents a 45-year-old African American female with persistent abnormal uterine bleeding post-initial UAE, underscoring the importance of strategic techniques during repeat embolization to ensure efficacy. The patient underwent a successful repeat UAE procedure, demonstrating its safety and effectiveness in treating abnormal uterine bleeding while preserving fertility. In this case, the presence of collateral vessels may have contributed to the previous treatment failure. Specific procedural techniques are discussed, and long-term monitoring is recommended for optimal outcomes.

Optimization of Minocycline-Containing Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Real-World Evidence Study.

The optimal dosage of minocycline remains unclear for Helicobacter pylori (H. pylori) eradication. We aimed to evaluate the efficacy and safety of four different regimens with minocycline and metronidazole compared to classical bismuth quadruple therapy for H. pylori rescue treatment. From March 2021 to March 2024, refractory H. pylori-infected patients with at least two previous treatment failures who received 14-day therapy with b.i.d. proton pump inhibitor 20 mg and bismuth 220 mg, plus tetracycline 400 mg q.i.d and metronidazole 400 mg q.i.d (BQT), or minocycline 50 mg q.i.d and metronidazole 400 mg q.i.d (PBMn4M4), or minocycline 50 mg t.i.d and metronidazole 400 mg t.i.d (PBMn3M3), or minocycline 50 mg b.i.d and metronidazole 400 mg q.i.d (PBMn2M4), or minocycline 50 mg b.i.d and metronidazole 400 mg t.i.d (PBMn2M3) were included in this retrospective study. H. pylori eradication was assessed by 13C-urea breath test at least 6 weeks after treatment. All adverse effects during treatment were recorded. Totally, 823 patients were enrolled: 251 with BQT, 97 with PBMn4M4, 191 with PBMn3M3, 108 with PBMn2M4, and 176 with PBMn2M3. The eradication rates of BQT, PBMn4M4, PBMn3M3, PBMn2M4, and PBMn2M3 were 89.2%, 87.6%, 91.6%, 88.0%, and 91.5%, respectively, by intention-to-treat analysis; 96.1%, 97.7%, 97.8%, 96.9%, and 97.6%, respectively, by modified intention-to-treat analysis; 97.1%, 97.5%, 97.7%, 96.8%, and 97.6%, respectively, by per-protocol analysis. Metronidazole resistance did not affect the efficacy of all groups. PBMn2M3 group achieved the greatest compliance and the fewest moderate and severe adverse events. The novel bismuth-containing quadruple therapy with a low dose of minocycline and metronidazole is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment with superior safety and compliance. ClinicalTrials.gov identifier: NCT06332599.

Comparative evaluation of postoperative pain and periapical healing after root canal treatment using three different endodontic sealers: A randomized controlled clinical trial.

A randomized controlled clinical trial to evaluate postoperative pain and investigate periapical healing after root canal treatment using eugenol, resin-based, and calcium silicate-based sealers (CSBSs) sealers. Sixty-three individuals diagnosed with apical periodontitis confirmed using cold test and electronic pulp tester, periapical pathology with periapical index score of 2 or more, previous endodontic treatment failure exhibiting a visual analog scale pain score of 3 or above, were enrolled in this investigation. The patients were randomly allocated into three groups and following biomechanical preparation, the canals were obturated using Meta CeraSeal, AH plus, and eugenol-based sealers. Postprocedural pain intensity was assessed at 24 h, 48 h, and 7 days, while periapical healing was evaluated at 3- and 6-month follow-ups. Statistical analysis was done using the Chi-square and Friedman's test. The mean of periapical lesions for Meta CeraSeal (4.7, 1.6), AH Plus (4.68, 3.19), 24 and eugenol-based (2.66, 1.75) at 3 months and 6 months, respectively. The mean & std. deviation of pain scores at 24 h for Meta CeraSeal (0.62 ± 1.857), AH Plus (1.62 ± 1.962), and eugenol-based (0.48 ± 1.250). At 48 h for Meta CeraSeal (0.33 ± 1.528), AH Plus (1.33 ± 1.798). On the 7th day, Meta CeraSeal (0.24 ± 1.091) and AH Plus (0.71 ± 1.384) for eugenol-based at 48 h, and on the 7th day, none of the patients had pain. Evaluation of the apical sealer puff displayed no suggestive variations (P = 0.634). Notably, no analgesics were taken. No suggestive dissimilarity was noted between eugenol, resin-based, and CSBSs sealers.

Outpatient ATG-free hematopoietic transplantation for aplastic anemia in limited-resource environments offers excellent results: Data from a single LATAM center

ObjectiveTo document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen. Material and methodsPatients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome. ResultsForty-one transplants were performed. Time between diagnosis and transplant was five months (1–104). Median age was 37 (range, 4–61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (p = 0.035) and EFS (p = 0.026). Previous treatment failure and age were not associated with lower OS (p = 0.115, p = 0.069) or EFS (p = 0.088, p = 0.5, respectively). ConclusionsHLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.

Efficacy of spironolactone in treating hidradenitis suppurativa in women of childbearing age: a single-center retrospective analysis.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent nodules that affect areas with a high density of apocrine sweat glands, such as the axillae and groin. Androgens are implicated in the pathophysiology of HS. Therefore, spironolactone, an antiandrogen therapy, is recommended. However, data on its use in women of childbearing age are limited, especially since its antiandrogenic effects may affect menstruation, fertility, and pubertal development. To evaluate the efficacy and safety of spironolactone in the treatment of hidradenitis suppurativa in women of childbearing age and to identify factors associated with treatment response. A retrospective analysis was conducted on female patients aged 12 to 50 with HS treated with spironolactone at Michigan Medicine dermatology clinics from 2000 to 2021. The patients' demographic data, HS characteristics, and spironolactone responses were examined. Statistical assessments were performed to determine the efficacy indicators. Of the 157 patients reviewed, 31 showed an improvement in treatment. Variables such as axillary involvement, previous treatment failures, and use of intralesional steroids were linked to a lack of improvement in spironolactone. Through adjusted multiple logistic regression analysis, a significant association was observed between improvement status and Hurley stage 3 (odds ratio = 0.15 [95% CI: 0.02-0.79], P = .036), suggesting that patients with Hurley stage 3 were 85% less likely to exhibit improvement in spironolactone therapy. The study's retrospective nature and reliance on single-center data can limit generalizability. The sample size is limited and therefore affects the study's statistical power. Thus, spironolactone may offer therapeutic benefits for HS in women of childbearing age. However, patients with severe disease (Hurley stage 3) had reduced response rates. Further prospective studies are recommended to validate these findings and determine the most suitable patient profile for spironolactone therapy for HS.

IMM2510, an anti-PD-L1/VEGF bispecific antibody fusion protein, in patients with advanced solid tumors: A phase I dose-escalation study.

e14506 Background: IMM2510 is a novel bispecific antibody fusion protein targeting PD-L1 and VEGF. The preclinical study demonstrated that IMM2510 induced significantly stronger anti-tumor activity than either monotherapy or combination of PD-L1 inhibitor and anti-VEGF antibody through blocking the PD-1/PD-L1 pathway and thus activate T cells and reducing VEGF-mediated tumor angiogenesis as well as an enhanced ADCC effect. We previously disclosed the preliminary clinical data of IMM2510, and here we further report safety and efficacy results of IMM2510 in the phase I dose escalation study. Methods: A phase I, multicenter, open-label, dose-escalation study, was designed to evaluate the safety, efficacy, recommended phase II dose (RP2D), and pharmacokinetics (PK) of IMM2510 in patients (pts) with advanced solid tumors. The study was designed with an accelerated titration followed by a standard 3+3 design. IMM2510 (0.007, 0.03, 0.1, 0.3, 1.0, 3.0, 6.0, 10.0, 20.0 mg/kg) was administered intravenously Q2W as monotherapy. Results: As of Dec 21, 2023, 33 pts had received IMM2510 at 9 dose levels (0.007-20.0 mg/kg), the median age was 57 years (range 36-74), the median prior line of therapy was 3 (range 1-13), and 27.3% pts received prior anti PD-1/PD-L1 inhibitor therapies. Treatment-related adverse events (TRAEs) occurred in 32 pts (97.0%). Most TRAEs were grade 1 or 2. The most common TRAEs (≥ 20%) of all grades were infusion related reaction (IRR) (72.7%), platelet count decreased (39.4%), anemia (33.3%) and diarrhea (21.2%). Grade ≥3 TRAEs occurred in 11 pts (33.3%). Grade ≥3 TRAEs (≥5%) were IRR (9.1%), platelet count decreased (6.1%), lymphocyte count decreased (6.1%) and diarrhea (6.1%). TRAEs leading to treatment discontinuation occurred in 3 pts (9.1%) which were IRR, hypersensitivity and pyrexia, respectively. No DLT occurred. In 25 response evaluable pts, 3 pts had confirmed PR: 1 pt with sq-NSCLC (onco-driver gene negative, previous IO treatment failure) at 3 mg/kg with tumor shrinkage 46% and still on the treatment with treatment duration over 20 months; 1 pt with sq-NSCLC at 10 mg/kg with tumor shrinkage about 32% along with treatment duration 9.4 months; 1 pt with thymus adeno-squamous carcinoma (PD-L1 CPS 80) at 20 mg/kg with tumor shrinkage over 53% and still remains on the treatment along with treatment duration 8.1 months. In addition, 7 pts with BOR SD and 4 of them had over 15% decreased tumor burden (1 cervical cancer at 3 mg/kg, 2 non-sq NSCLC at 10 and 20 mg/kg respectively, 1 ovarian cancer at 20 mg/kg). The half-life of IMM2510 in 20.0mg/kg dose group was around 6.8 days. The RP2D was determined to be 20.0 mg/kg. Conclusions: IMM2510 is well tolerated in general and preliminary anti-tumor activity in solid tumors is encouraging. The phase Ib/II is ongoing to enroll patients. Clinical trial information: NCT05972460 .

Treatment failure is a key factor in the development of Helicobacter pylori resistance.

Helicobacter pylori eradication failure influences its antibiotic resistance. This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach towardantidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 μM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 μM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

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.

Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials

IntroductionMigraine headache is a significant health problem affecting patients’ psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have...

Comparative effectiveness of baricitinib and alternative biological DMARDs in a Swiss cohort study of patients with RA

ObjectivesThis observational study compares the effectiveness of baricitinib (BARI), a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), with alternative biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA), from a prospective,...

Electrochemotherapy in Aggressive Hemangioma of the Spine: A Case Series and Narrative Literature Review.

(1) Background: this case series and literature review aims to evaluate the efficacy and safety of electrochemotherapy in the management of aggressive spinal hemangiomas, presenting two distinct cases. (2) Methods: we present two cases of spinal aggressive hemangioma which were refractory to conventional treatments and underwent electrochemotherapy. Case 1 involves a 50-year-old female who presented with an aggressive spinal hemangioma of L1, who previously underwent various treatments including surgery, radio-chemotherapy, and arterial embolization. Case 2 describes a 16-year-old female with a T12 vertebral hemangioma, previously treated with surgery and stabilization, who faced limitations in treatment options due to her young age and the location of the hemangioma. (3) Results: in Case 1, electrochemotherapy with bleomycin was administered following the failure of previous treatments and resulted in the reduction of the lesion size and improvement in clinical symptoms. In Case 2, electrochemotherapy was chosen due to the risks associated with other treatments and was completed without any adverse events. Both cases demonstrated the potential of electrochemotherapy as a viable treatment option for spinal hemangiomas, especially in complex or recurrent cases. (4) Conclusions: electrochemotherapy with bleomycin is a promising treatment for aggressive spinal hemangiomas when conventional therapies are not feasible or have failed. Further research is needed to establish definitive protocols and long-term outcomes of electrochemotherapy in spinal hemangioma management.

Approaches to the Treatment of Patients with Myelofibrosis and Polycythemia Vera with Constitutional Symptoms in Real-World Clinical Practice in the Russian Federation: Intermediate Results of a Multi-Center Observational Prospective Clinical Study

Aim. To describe the methods of drug therapy implemented for the disease control in patients with polycythemia vera (PV) and myelofibrosis (MF) as well as to analyze manifestations and severity of the disease symptoms in real-world clinical practice.&#x0D; Materials &amp; Methods. The analysis focused on the data of 1229 patients. In 629 (51.18 %) patients, PV was diagnosed, MF was identified in 521 (42.39 %) patients. The diagnosis of 79 (6.43 %) patients was not reported. Early stage of primary MF (PMF) was detected in 182 (34.93 %) patients, PMF fibrosis stage was identified in 251 (48.18 %) patients, post-polycythemic MF was registered in 61 (11.71 %) patients, and 13 (2.5 %) patients showed post-thrombocythemic MF. In 14 (2.69 %) patients, MF type was not reported. By the time of diagnosis, the median age of PV patients was 56 years (range 17–86 years), and that of MF patients was 55 years (range 16–83 years) (p = 0.022). The proportion of women among PV patients was 57 %, among MF patients it was 65 % (p = 0.0065).&#x0D; Results. The assessment of thrombotic complication risk in PV showed that 51.01 % (n = 302) of patients belong to the low-risk, 39.86 % (n = 236) belong to the intermediate-risk, and only 9.12 % (n = 54) of patients belong to the high-risk groups. Distribution of MF patients between risk groups demonstrates favorable prognosis for most patients. The group of low and intermediate-1 risks includes 56.43 % (n = 294) patients according to the prognostic scoring system IPSS and 68.52 % (n = 357) according to the prognostic scoring system DIPSS. In the vast majority of cases, patients received hydroxycarbamide therapy: 81.81 % (n = 832) in the total cohort, 83.33 % (n = 465) in the PV group, and 79.96 % (n = 367) in the MF group. Interferon-α was administered to 19.71 % (n = 110) of PV patients and 29.85 % (n = 137) of MF patients. Ruxolitinib was assigned to 3.14 % (n = 19) of PV patients and 21.35 % (n = 98) of MF patients.&#x0D; Conclusion. Regular monitoring of the PV and MF course and treatment efficacy can provide recommendations for adequate change of therapy in case of the failure of previous treatment. It should be emphasized that the timely switch to the second-line therapy results in reduced disability and mortality among PV and MF patients with myeloproliferative neoplasms.

Indications and technique of open vascular surgical revascularization of visceral arteries in mesenteric ischemia

Open revascularization for mesenteric ischemia has retained asignificant value despite the increasing importance and use of endovascular techniques. Surgical procedures such as retrograde embolectomy, thromboendarterectomy and visceral bypass are indispensable components of the therapeutic armamentarium, particularly in cases of multisegmental vascular involvement, failure of previous endovascular treatment and concomitant presence of peritonitis, shock or multiorgan failure. In this context, preoperative multiphase computed tomography (CT) angiography is essential for the planning and outcome of visceral revascularization. This article summarizes the indications, technique, and results of the most important open surgical procedures.

539 - Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult atopic dermatitis patients in Japan treated with dupilumab: Real-world insights one year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study –demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-­inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; &amp;gt;21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab ­treatment.

DLPL Sphincter Saving Laser Surgery for Complex Anal Fistula - A Gold Standard Procedure. Study of 40 Cases

Introduction: Complex anal fistula (CAF) is a complex condition to treat because of the possibility of recurrence and impoverished continence. DLPL (Distal laser proximal ligation), is a novel approach to treating difficult anal fistula that involves suturing the proximal portion of the fistula tract close to the internal opening and using a diode laser to close the distal part of the fistula tract. This study aimed to evaluate the clinical efficacy and safety of DLPL Sphincter Saving Laser Surgery for Complex Anal Fistula. Aim of the study: The aim of this study was to evaluate the clinical efficacy and safety of DLPL Sphincter Saving Laser Surgery for Complex Anal Fistula - A Gold Standard Procedure in a study of 40 cases. Methods: This study was a prospective observational study that investigated the outcomes of DLPL (Distal Laser Proximal Ligation) for patients with complex anal fistula. The patients met clinical diagnosis of complex anal fistula according to the Parks classification, age of 10 years or more, and failure of previous conservative or surgical treatments. The patients were followed up at 3 and 6 months after the surgery, and assessed using fistulogram, endo anal ultrasound, MRI. Result: The study enrolled 40 patients (35 males and 5 females) with mean age being 31.25 years. 31 (77.50%) patients had non-specified histopathology. 2 (5.00%) patients had Chron’s disease, 2 (5.00%) patients had F.B Granuloma, and 5 (12.50%) patients had Tuberculosis. The patients were assessed using fistulogram, endo anal ultrasound, MRI. After 6 months, the patients were followed up and 38 (95.00%) patients had no recurrence, only 2 (5.00%) patients had recurrence. Conclusion: The results showed high success rate and low complication rate of DLPL for complex anal fistula. Therefore, this study concluded that DLPL is a safe and effective sphincter-saving technique for complex anal fistula, and that it may be considered as a gold standard procedure for this challenging c

P1049 Effectiveness and safety of subcutaneous infliximab in Crohn’s disease patients with immunogenic failure of intravenous infliximab

Abstract Background Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous compared to intravenous infliximab. However, it is unknown whether re-exposure of patients with immunogenic failure of IFX to its subcutaneous formulation is safe and effective. Here, we analysed the safety and effectiveness of subcutaneous IFX (CT-P13) in patients with Crohn’s disease (CD) and history of secondary loss of response of intravenous IFX due to anti-drug antibodies (ADA). Methods In a retrospective analysis conducted at medical centers in Germany (Dresden) and the Czech Republic (Prague), patients with clinical (Harvey-Bradshaw Index ≥ 5) and/or biochemical (faecal calprotectin &amp;gt;250 µg/g) active CD and previous treatment failure in the context of IFX immunogenicity underwent re-exposure to subcutaneous IFX. Treatment was initiated with either 4 subcutaneous injections 120 mg CT-P13 weekly followed by biweekly injections, or directly with 120 mg CT-P13 subcutaneous biweekly. Harvey-Bradshaw Index, faecal calprotectin, IFX serum concentration and ADA were assessed until month 12. Results Twenty CD patients were included (table 1). The majority of patients (90 %) had previous treatment with ≥ 3 biologics. 75% and 50 % of patients continued IFX treatment until month 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients (10%) discontinued IFX due to delayed hypersensitivity. Lack of treatment effectiveness led to infliximab withdrawal in 7 cases (35%) and one patient (5%) was lost to follow up after month 6. IFX serum concentrations increased from baseline (median 0 µl/ml ± 0 interquartile range/IQR) until month 12 (median 22.8 µl/ml, 10.0 IQR), while ADA levels decreased (50.6 AU/ml, 48.3 IQR and 0.0 AU/ml, 0 IQR at baseline and month 12, respectively). Clinical remission at month 12 was observed in 27% and biochemical remission in 38% of patients with active Crohn's disease at baseline. 67 % of patients with clinical inactive Crohn's disease at baseline remained in clinical remission until month 12. Conclusion Subcutaneous infliximab after previous failure and immunogenicity of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.