Subcutaneous Form Research Articles

P0825 Combination of advanced therapies in anal fistulas of Crohn’s disease: efficacy, tolerance and predictive factors

Abstract Background The aim of CombioLAP study was to evaluate the efficacy and tolerance of a combination of advanced therapies (combiotherapy) in fistulizing anoperineal lesions (APL). Methods We conducted a retrospective study on patients treated for at least 6 months with a combiotherapy for fistulizing APL. The primary outcome was the complete clinical remission (defined as a closure of all fistulae external openings without any discharge or pain on pressure). The secondary outcomes were to describe in detail: - type of combiotherapies - complete radiological remission (defined by a MAGNIFI CD score < 6) - tolerance and perception of treatment - factors associated with clinical failure Results We included 33 patients (57.6% men, mean age 38.3 ± 13.1 years) of whom 27.3% were active smokers and 48.5% had extra-digestive manifestations. The mean time for the progression of APL was 7.8 ± 6.2 years. Half of the patients had more than one external fistula opening. Patients had undergone a mean of 5.3 ± 3.4 proctological surgeries; 53.7% of them had already had at least one fistula obturation surgery; 84.9% were in partial response or had failed at least two lines of advanced therapies. After a median follow-up of 27.4 months [19.1-44.0] under combiotherapy, 48.5% of patients were in complete clinical remission (53.3% with associated obturation surgery). Combiotherapy contained infliximab in 88% of cases (optimized in 82% of cases and in subcutaneous form in 52% of cases) with ustekinumab in 84% of cases (optimized in 92% of cases). An immunosuppressant was additionally associated in 21.2% of patients and long-term antibiotic therapy in 24.2% of patients (2 for refractory APL and 6 for associated hidradenitis suppurativa). Complete radiological remission was observed in 28.6% of patients. Treatment tolerance was defined as good to very good in 90.1% of cases. Minor adverse effects were reported in 5 patients (15.2%). No infectious or neoplastic adverse effects were reported. Improvement under treatment was considered obvious by patients in 57.6% of cases and partial in 39.4% of cases. Associated anal ulcerations (OD [95% CI] 0.18 [0.04-0.94], p=0.042) and long-term antibiotic therapy (OD [95% CI] 0.10 [0.01-0.90], p=0.040) were predictive factors of clinical failure. Conclusion In refractory fistulizing APL, the most used combiotherapy was infliximab associated with ustekunimab in optimized doses, allowing complete clinical remission in 48.5% of cases and complete radiological remission in 28.6% of cases. The safety profile was good and furthermore there was good perception of treatment by most patients. Associated anal ulcerations and long-term antibiotic therapy were poor prognostic factors.

Comparison of Long-Term Antibody Titers in Calves Treated with Different Conjunctival and Subcutaneous Brucella abortus S19 Vaccines.

Brucellosis is still the most common zoonosis worldwide despite advanced technology and animal husbandry. Since there is still no effective Brucella vaccine for humans, it is crucial to control the disease in ruminants through eradication and vaccination. Although some countries around the world have achieved this circumstance, every country aims to become free of Brucellosis through vaccination, animal movements, and various eradication measures. For this purpose, the Brucella abortus S19 strain has been used safely for about 100 years. However, due to the O-polysaccharide (OPS) antigen in its structure, the antibody response created by the vaccine causes confusion in serological tests. For this purpose, researchers have provided both mucosal immunity and short-term antibody response by using the B. abortus S19 vaccine in conjunctival form instead of subcutaneous form. This study aimed to determine how long the post-vaccination titer levels persisted in animals vaccinated with vaccines from 3 different companies and different routes. In this study, a total of 115 calves aged 3 to 4.5 months were created in five groups, with 23 animals in each group: group 1 (vaccine brand A), group 2 (vaccine brand B), and group 3 (vaccine brand C) received the two-dose conjunctival vaccine, group 4 received the single-dose subcutaneous vaccine (vaccine brand C), and group 5 received the subcutaneous vaccine (vaccine brand C) plus the booster dose conjunctival vaccine (vaccine brand B). Brucellosis antibody titers were monitored each 21 days until the cattle were 26-28 months old. The collected sera were analyzed using the Rose Bengal Plate Test (RBPT), Serum Agglutination Test (SAT), and Complement Fixation Test (CFT), which are the preferred serological methods for Brucellosis eradication plans worldwide. In the conjunctival vaccination groups, only 3 (13%) of the animals in group 1 developed antibody titers one month after vaccination, and there was no antibody response detected against Brucellosis in group 2 and group 3. In animals that were stimulated conjunctivally, the threshold value of 30 International CFT Units (ICFTUs) (for distinguishing between infective titers and vaccination titers) was observed in one animal each in group 1 and group 2 and 0 animal in group 3. It was found that antibody titers turn to Brucellosis negative in all conjunctival vaccine groups at 7 months after vaccination. In groups 4 and 5, the first-month serological screening detected over 30 ICFTUs in 17 (89.47%) animals and 16 (69.5%) animals, respectively. In group 4, CFT titers were found to fall below 30 on the 17th month and 9.3 on the 22nd month. On the 14th month, the CFT titers of group 5 were found to be below 30, and all animals in this group turned negative after the 19th month. It was found that the single dose B. abortus S19 subcutaneous vaccination in calves caused persistent antibodies in 5% of the population. It is believed that persistent and high antibody titers created by subcutaneous vaccines will cause false positivity and create confusion in Brucellosis eradication programs. Therefore, although there is no clear distinction between vaccinated and infected animals, it has been observed that conjunctival Brucellosis vaccines create more stable antibody titers and decrease rapidly compared to subcutaneous vaccines. Based on the results of this study and the advantages of conjunctival vaccines, more effective eradication programs and antibody monitoring can be carried out in vaccinated herds where Brucellosis outbreaks are observed.

Applications of Semaglutide for Various Diseases

Semaglutide is a gluten-like peptide 1 (GLP-1) agonist which is responsible for improving blood sugar control and losing weight. It is clinically approved by the FDA for treatment of type 2 diabetes mellitus and is designed in subcutaneous or oral dosage form. Some other diseases share common conditions with obesity and diabetes such as a high blood sugar level and insulin resistance. These factors along with some neuron issues are responsible for neurodegenerative diseases. Obesity and diabetes are two common worldwide health issues. A number of trials have been conducted to estimate the prevalence and drug effects. Scientists also study related diseases such as Non-alcoholic fatty liver disease to verify the usefulness of treatments. Semaglutide is one of the drugs being measured whether has a potential effect on these diseases. Some pre-clinical studies have indicated its therapeutic potential in non-alcoholic steatohepatitis and neurodegenerative disorders. Semaglutide has proved to be effective in treating lots of disorders, especially diabetes and obesity. However, for other diseases, it still remains uncertain even if there are some studies already tested the effectiveness. Much more detailed and considerate studies should be conducted to verify the impact. Semaglutide, the GLP-1 receptor agonist, has shown a positive impact in treating different diseases. Researchers have tested hepatoprotective and neuroprotective activity in animal and human trials to get more reliable data. It turns out that semaglutide improves insulin resistance and reduces blood sugar levels. It also protects dopaminergic neurons and reduces aggregated α-synuclein which improves Parkinson’s disease and Alzheimer’s disease conditions.

Comparison of intravenous and subcutaneous administration of ocrelizumab. Time and motion study

Introduction and objective: Ocrelizumab is used in multiple sclerosis treatment and is available in intravenous and subcutaneous forms. In Poland, only the intravenous form is currently reimbursed. The subcutaneous form offers a shorter administration time, potentially benefiting both healthcare providers and patients. This study evaluates the impact of the different forms of ocrelizumab administration on medical facility workflow and costs. Materials and methods: A survey was conducted in six medical centres involving 329 patients treated with ocrelizumab in 2023, with 46 patients receiving the subcutaneous form of the drug. The study assessed the complete drug administration process, including premedication, preparation, administration, and post-administration observation. The comparison between the two forms of ocrelizumab focused on the costs associated with drug administration, the time patients spent at the medical centre, and the efficiency of the drug administration process. Results: The administration costs of the subcutaneous form were significantly lower (96.80 PLN) than the intravenous form (224.32 PLN). The time patients spent at the medical centre was greatly reduced for the subcutaneous form (56 minutes) compared to the intravenous form (242 minutes). Efficiency in drug administration was also higher for the subcutaneous (26.88) than the intravenous form (2.62). Conclusions: The study highlights the substantial benefits of the subcutaneous form of ocrelizumab over the intravenous form. These advantages are noticeable from both the healthcare provider’s and patient’s perspectives, underscoring the potential for improved efficiency and patient experience with the subcutaneous form.

Choice of therapy for HER2-positive metastatic breast cancer in real clinical practice: analysis of physician preferences in Russian Federation

Metastatic breast cancer still remains an incurable disease, requiring lifelong treatment. Introduction of targeted therapy into clinical practice has radically changed treatment approaches of HER2-positive breast cancer, making it possible to significantly increase the life expectancy. The treatment algorithm for HER2-positive metastatic breast cancer appears to be quite clear and is reflected in both international and Russian recommendations. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of Her2-positive breast cancer” was conducted. This publication presents results dedicated to the treatment of metastatic HER2-positive breast cancer. 50 specialists from 43 cities took part in the survey. Only heads of departments or their deputies who were personally involved in determining the treatment for patients were allowed to participate. Expertise of this level allows us to reliably assess the actual clinical practice that has developed in the Russian Federation and determine directions for optimizing therapeutic approaches. Despite ongoing questions about the availability of drugs, doctors primarily focus on the effectiveness of treatment. The main first-line therapy in the Russian Federation is the combination of trastuzumab with pertuzumab. However, experts noted that in conditions of unlimited access to drugs, the number of prescriptions for this regimen in the first line would increase by 13%. Doctors also agree that the use of a subcutaneous form of this combination of drugs would optimize the treatment process. Trastuzumab emtansine remains the standard of second-line therapy and, according to the survey results, almost all patients for whom it is indicated receive this type of therapy. Experts predict more frequent use of trastuzumab emtansine in first-line therapy, given the widespread use of neoadjuvant regimens with pertuzumab. The most significant changes are expected in the third line of therapy with the introduction of the new conjugate – trastuzumab deruxtecan. The survey results demonstrate high awareness and commitment of physicians to modern principles of treatment of HER2-positive mBC.

The Effect of Two Types of Subcutaneous Heparin Injections on Pain, Ecchymosis, Hematoma and Drug Absorption: A Quasi-Experimental Study.

Subcutaneous heparin injections sometimes cause pain, ecchymosis, and hematoma. The prevalence of complications depends on the injection site, technique, and drug absorption. This study investigated the effect of two types of subcutaneous heparin injections on pain, ecchymosis, and hematoma as well as drug absorption rates. The study is a quasi-experimental. The research was conducted between September 2021 and May 2022. The sample consisted of 122 patients treated in the general surgery clinic of a university hospital in the Black Sea region of Türkiye. We used ultrasonography (USG) to measure the subcutaneous tissue thicknesses of the sites before heparin injections. We used the tissue-releasing technique (TRT) to administer heparin injections to 68 participants (Group TRT). We used the tissue-pinching technique (TPT) to administer heparin injections to 54 participants (Group TPT). We administered all injections into the arm or abdomen. We used a "Subcutaneous Injection Form" to collect data. We monitored all participants for the injection site, drug absorption after 1 day, pain, ecchymosis, and hematoma for 3 days. There was no significant difference in the prevalence of pain, ecchymosis, and hematoma between the groups (p > 0.05). Most injections into the arm and abdomen resulted in drug absorption. However, one in ten injections into the arm resulted in the needle reaching the muscle rather than the subcutaneous tissue (11.7%). Abdominal injections caused no complications. The drug was administered in the right place in abdominal injections. The tissue-releasing and TPTs are not superior to each other as far as drug absorption, pain, ecchymosis, and hematoma are concerned. In this study recommend pinching the tissue or using the abdominal region in cases where the subcutaneous tissue thickness is less than 15.96 mm. The nurse should consider Body Mass Index before choosing the right subcutaneous heparin injection site and the correct injection technique.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration.

Compared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination. Our goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide. We collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR). We identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren's contracture (ROR: 46.85) in oral semaglutide. Our study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Oral Insulin Delivery: A Review on Recent Advancements and Novel Strategies.

Due to the lifestyle of people in the community in recent years, the prevalence of diabetes mellitus has increased, so New drugs and related treatments are also being developed. One of the essential treatments for diabetes today is injectable insulin forms, which have their problems and limitations, such as invasive and less admission of patients and high cost of production. According to the mentioned issues, Theoretically, Oral insulin forms can solve many problems of injectable forms. Many efforts have been made to design and introduce Oral delivery systems of insulin, such as lipid-based, synthetic polymer-based, and polysaccharide-based nano/microparticle formulations. The present study reviewed these novel formulations and strategies in the past five years and checked their properties and results. According to peer-reviewed research, insulin-transporting particles may preserve insulin in the acidic and enzymatic medium and decrease peptide degradation; in fact, they could deliver appropriate insulin levels to the intestinal environment and then to blood. Some of the studied systems increase the permeability of insulin to the absorption membrane in cellular models. In most investigations, in vivo results revealed a lower ability of formulations to reduce BGL than subcutaneous form, despite promising results in in vitro and stability testing. Although taking insulin orally currently seems unfeasible, future systems may be able to overcome mentioned obstacles, making oral insulin delivery feasible and producing acceptable bioavailability and treatment effects in comparison to injection forms.

Two-year treatment persistence with subcutaneous abatacept in rheumatoid arthritis: results from the French cohort of the ASCORE study.

While multiple studies have investigated treatment persistence rates with intravenous abatacept, limited information is available about real-world treatment continuation with the subcutaneous form. The international ASCORE study described the characteristics and treatment persistence of real-world patients with rheumatoid arthritis (RA) receiving subcutaneous abatacept. This article presents the findings of the French cohort. This was an observational study in French RA patients who initiated subcutaneous abatacept between August 2014 and January 2017. The primary endpoint was treatment maintenance at 2 years, analysed according to the number of previous biologic therapies. Of 546 evaluable patients, 281 (51.5%) were biologic-naive, 265 (48.5%) had experienced failure with 1 (n=134; 24.5%) or ≥2 (n=131; 24.0%) biologic therapies. At enrolment, patients who had experienced failure with ≥1 biologic therapy had more erosions and a longer duration of RA compared with biologic-naive patients, but had comparable mean disease activity scores. Overall, 43.0% of patients (95% confidence interval 38.6-47.2) were still taking subcutaneous abatacept at 2 years, which was comparable with that in other countries participating in ASCORE. The abatacept persistence rate was higher in biologic-naive patients (48.8%) than in those with 1 (40.9%) or ≥2 (32.8%) biologic therapy failures. The main reason for discontinuing abatacept was lack of efficacy (46.6%). In current practice in France, the rate of subcutaneous abatacept persistence at 2 years was comparable with that of the intravenous form. Treatment persistence was higher when abatacept was used as first-line versus later-line biologic therapy.

Review of clinical pharmacokinetics and pharmacodynamics of clonidine as an adjunct to opioids in palliative care.

Clonidine is an α-adrenoceptor agonist acting on receptors in the brain and peripheral tissues, leading to a reduction in sympathetic outflow and release of certain neurotransmitters. Clonidine has multiple uses across various medical conditions. One of its uses is as adjuvant to anaesthetic and analgesic agents specially opioids, mostly administered through intravenous and epidural routes. The opioids, effective in cancer pain management, are associated with various side effects such as sedation, pruritus, constipation, nausea, respiratory depression, tolerance and dependence. Combination of clonidine with opioids seems to help to achieve better pain management and less need of opioids. Use of clonidine in palliative care has been less common, but it is gradually gaining recognition for its potential benefits in managing symptoms like cancer pain and agitation. This combination approach has been explored in palliative care settings, including cancer pain and agitation, where patients experience complex and refractory symptoms. It seems to be well tolerated and gives better symptom relief. The available literature on clonidine's use in cancer pain and agitation management, especially in subcutaneous form, is limited and outdated. Therefore, the optimal dosing, safety profile and overall effectiveness of subcutaneous clonidine requires further exploration through prospective research studies.

The impact of an ‘evergreening’ strategy nearing patent expiration on the uptake of biosimilars and public healthcare costs: a case study on the introduction of a second administration form of trastuzumab in The Netherlands

In this paper, we explore dynamic market share and public healthcare costs of trastuzumab’s evergreening (subcutaneous) variant during introduction of trastuzumab’s competitive biosimilar variants in the Netherlands. We used a time series design to assess dynamic market share of trastuzumab’s evergreening variant after introducing trastuzumab’s biosimilar variants, focusing on the number of treatments and patients. The public healthcare costs of this evergreening strategy were estimated using administrative claims data. Our results show that the original trastuzumab was completely replaced by the subcutaneous and biosimilar variants. The uptake of the subcutaneous form peaked at 50% market share but after the introduction of biosimilars progressively reduced to a market share of 20%, resulting in a more competitive market structure. The public healthcare costs for trastuzumab significantly decreased after the introduction of the biosimilars. After the introduction of the biosimilars, a substantial price drop is visible, with the subcutaneous version, still under patent, also falling sharply in price but less strongly than the iv/biosimilar version. As the costs are publicly funded, we recommend a more explicit societal debate to consider if the potential benefits of subcutaneous Herceptin® (and other similar medicines) are worth the additional costs, and at which price it should be reimbursed as the part of the benefit package.

Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID.

Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

A case report on bortezomib-induced paralytic ileus

Bortezomib is the first anticancer proteasome inhibitor used in the initial treatment of multiple myeloma in combination with cyclophosphamide and dexamethasone. Subcutaneous and intravenous forms of bortezomib are available. The common adverse drug reactions (ADRs) associated with bortezomib include peripheral neuropathy, fatigue, neuralgia, dizziness, diarrhea, constipation, and abdominal pain. Paralytic ileus is a rare ADR of bortezomib. We report the case of a patient with multiple myeloma who developed paralytic ileus and presented with abdominal distension and constipation; all of which resolved with medical attention once the medication was stopped, indicating a clear causal link.

In vitro evaluation of Sporothrix brasiliensis biotherapic: complete results

Background: Sporothrix brasiliensis is a fungus that affects animals, mainly felines, and humans. The infection can present as subcutaneous or disseminated form in the organism. Rio de Janeiro, Brazil, is a state with high prevalence of cases in felines. Currently, the standard treatment is realized during a long period and using itraconazole, that causes important adverse effects. Objective: The aim of this research was to evaluate in vitro effect of Sporothrix brasiliensis biotherapic in the fungus used to prepare this medicine, also considering the association to itraconazole. Methodology: Yeast cells of S. brasiliensis (ATCC MYA 4823) were cultured in Brain Heart Infusion (BHI) during 3 to 5 days. The biotherapic 30 DH was prepared according to Brazilian Homeopathic Pharmacopoeia, using 5 x 107 yeasts/mL. Two biotherapics were prepared: using inactivated fungus by autoclave (Sb1) and viable yeasts (Sb2). Both biotherapics were evaluated individually and associated to itraconazole. The control groups were: water, diluted water, water 30 DH, and dimethylsulfoxide (vehicle to dissolve itraconazole), and itraconazole. The minimum inhibitory concentration (MIC) experiments were carried out, considering the CLSI (Clinical &amp; Laboratory Standards Institute) guidelines. Results: The treatments using only biotherapic did not reduced the yeast viability, as observed in the controls. However, the higher concentrations of itraconazole and of this drug associated with biotherapic reduced the viability of S. brasiliensis. Then, the observed effect was attributed to itraconazole. Conclusion: As expected, it was not detected the effect of both biotherapic in the viability of microorganism itself, due to the integrality aspects of homeopathy, because the homeopathic medicine emphasizes the whole organism’s response to the symptoms presented. Then, the next step is to evaluate the biotherapic in an in vivo model, that will be a complete organism representing the host to this infection.

Post COVID - 19 Infection Diffuse Patch Granuloma Annulare in a Female Patient with Rheumatoid Arthritis: A Case Report

Introduction: Granuloma Annulare (GA) is a benign, usually self-limited, inflammatory granulomatous skin disorder of unknown etiology and with a diversity of clinical variants. Genetic factors, associations with predisposing diseases along with several triggers such as certain infections and vaccines, have been described, SARS-CoV-2 virus being one of them. Case Presentation: Localized, generalized and subcutaneous forms of GA have been reported following either SARS-CoV-2 infection or vaccination against the virus. Herein we present a case of diffuse patch GA in a middle-aged female patient with medical history of rheumatoid arthritis, one month after catching COVID -19 despite being fully vaccinated against the virus. Discussion: Overall, taking into account the relevant literature, the occurrence of GA after infection with SARS-CoV-2 as well as after vaccination seems to be attributed to the activation of an immunologic reaction rather than to the direct effect of the virus on the skin lesions, with the latest also appearing in the form of diffuse patch rashes. Conclusion: Dermatologists should be aware of such lesions appearing after COVID-19 infection or even vaccination especially in patients with autoimmune diseases.

OP19 Monoclonal Antibodies in Oncology: A Comparative Analysis of Subcutaneous Form Use Between Paris University Hospitals (AP-HP) Versus French Hospitals

OP19 Monoclonal Antibodies in Oncology: A Comparative Analysis of Subcutaneous Form Use Between Paris University Hospitals (AP-HP) Versus French Hospitals

Effects of Intermittent Fasting on Patients with Immune Thrombocytopenia (ITP) Receiving TPO-RA : Multicenter Mixed-Design Study

Introduction The thrombopoietin receptor agonists (TPO-RAs), such as Avatrombopag (AVA), Eltrombopag (ELT), and Romiplostim (ROM), have, in recent years, changed ITP treatment, showing that there is both increased platelet destruction and suboptimal platelet production in ITP. ELT and AVA are oral drugs, while ROM is subcutaneous, and studies have shown that absorption of ELT can be affected by meals. Thus, for optimum absorption, patients are counseled to take it on an empty stomach at least 1 hour before or 2 hours after a meal and at least 2 hours before and 4 hours after calcium-containing meals. However, in Muslim countries where the 16/8 type of intermittent fasting is practiced by religion, the scheduling of drug consumption can be affected. Objective The aim of this study is to evaluate the effect of fasting on patients with ITP receiving different Thrombopoietin receptor agonists (TPO-RAs) brands. Methods A Multicenter, mixed design study was performed in which we interviewed Muslim patients (n = 100) who were 18 years of age or older in Qatar, Kuwait, and Saudi Arabia and fasted Ramadan while receiving TPO-RA treatment between the years of 2015 and 2023. Clinical and biological parameters are recorded using using a standardized patient form. Fasting status was confirmed by a telephone call to each patient. Patients' responses were retrospectively evaluated before, during, and after Ramadan. A statistically significant result was identified with a P-value of &amp;lt; 0.05. Bleeding tendency was also evaluated as either no bleeding, minor cutaneous and mucosal bleeding, or life-threatening bleeding involving major organs (i.e., central nervous system, gastrointestinal, or genitourinary). Results A hundred patients were identified who matched our inclusion criteria for this study. Platelet responses were different among the 3 products, and statistical significance was attributed to the product's compromised efficacy due to disturbed meal schedules and decreased absorption. For patients on AVA, the drug efficacy was not directly affected by meal schedule and absorption but instead was affected by patient compliance. The mean platelet count before Ramadan was estimated at 146.11 ± 111.76, while during Ramadan it dropped to 131.7 ± 107.6. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference 146.11 ± 111.76 vs. 134.17 ± 60.9. For patients on ELT, the mean platelet count before Ramadan was estimated at 120.02 ± 59.7, while during Ramadan it dropped to 100.8 ± 68.16. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference 120.02 ± 59.7 vs. 136.04 ± 74.86. For patients on ROM, the mean platelet count before Ramadan was estimated at 122.68 ± 80.57, while during Ramadan it was 130.94 ± 84.96. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference but an increase in platelet count 122.68 ± 80.57 vs 212.0 ± 113.72. Only 3% (3 patients on ELT) of the patients fasting during Ramadan experienced bleeding episodes. 2 of which experienced minor bleeding (ecchymosis and gingival bleeding), and 1 had major bleeding episodes (Lt. hemorrhagic infarction). 47% of the patients experienced a complete response (PLT&amp;gt;100x10 9) among the three products, and 17% experienced a partial response (PLT 51-100x10 9) 36.6% of the patients on AVA showed a complete response, 46.15% of patients on ELT, and 63.15% of patients on ROM. Conclusion TPO-RAs achieve target platelet counts in adult ITP patients. However, the absorption of ELT is highly affected by food consumption, and thus it is critical to adhere to the instructions given on how the dose should be adjusted and consumed on an empty stomach. AVA absorption didn't show compromise with food consumption, and its efficacy may depend only on patient's compliance. ROM showed better adherence to the medication schedule compared to ELT, contributing to its subcutaneous form and a tailored home visit program given weekly by trained nurses, enhancing patient compliance. The general tolerability and efficacy of TPO-RAs may be reflected on incidence of no major bleeding and the better efficacy of AVA and ROM, which are not affected by fasting.

THU520 Successful Treatment Of Ectopic ACTH From Metastatic Gastrinoma With Temozolomide Monotherapy

Abstract Disclosure: A. Syeda: None. A. Khan: None. D. Larosa: None. P. Kunz: None. B. Esayag-Tendler: None. Background: Temozolomide is a promising therapeutic agent for the treatment of refractory ACTH-secreting pituitary tumors. However, its role in the management of ectopic ACTH secretion due to neuro endocrine tumors (NETs) has not been well elucidated. Case: A 46-year-old man with a refractory functional pancreatic NET/ high grade metastatic gastrinoma, post distal pancreatectomy and splenectomy, briefly on everolimus therapy, presented with altered mentation and worsening edema. Clinically he had proximal muscle weakness, anasarca and hypokalemia with a potassium of 2.8mmol/L (n:3.6-5.1 mmol/L). Further work up revealed AM cortisol 79.6 ug/dL (n:7-23 ug/dL), 24-hour urine cortisol was 1820 ug/d (n: &amp;lt; 60 ug/d), ACTH 807 pg/mL (n:7.2-63.3 pg/mL) and gastrin level &amp;gt;10,000 pg/mL (n:0-100 pg/mL). Imaging studies of the brain, chest, abdomen, and pelvis were unremarkable. Octreotide infusion at 100 mg/hour was started with a goal to decrease gastrin and ectopic ACTH production. There was no response to Octreotide even after 5 days of continuous infusion, hence it was switched to subcutaneous injection form to control diarrhea. Lutathera/Peptide receptor radionuclide therapy was considered but held off due to the patient's delirium. As hypercortisolism is associated with multiple risks including thromboembolic events, rapid reduction of cortisol biosynthesis was achieved with Ketoconazole. Other options to inhibit steroidogenesis were available; the goal was to decrease both ACTH and Gastrin levels and for this reason Temozolomide was started. It crosses the blood-brain-barrier and hence was a preferred agent in this patient as he was noted to have atypical cells in the CSF. He received Temozolomide 150 mg/m² for 5 days of a 28-day cycle. Subsequently, AM cortisol decreased to 3.4 ug/dL, ACTH and gastrin started to trend down to 144 pg/mL and 3505 pg/mL respectively. Thereafter, the patient was given steroids and ketoconazole as part of a block and replace strategy to avoid adrenal insufficiency and hypercortisolism respectively. Temozolomide was very well tolerated; there were different reasons to hold Capecitabine including severe thrombocytopenia. Bilateral adrenalectomy was discussed but deferred as the ACTH levels decreased. Clinically, the patient reported improved muscle strength, edema and weight decreased significantly. The hospital stay was complicated by several other comorbidities which were managed appropriately by a multidisciplinary approach. Conclusion: Temozolomide should be considered in ACTH producing NETs refractory to conventional treatment strategies. Presentation: Thursday, June 15, 2023

Allergic Rhinitis.

Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment.

Buprenorphine: two adolescent case reports of bridging the transmucosal form to the extended-release subcutaneous injectable form

According to the Centers for Disease Control and Prevention (CDC), 100,306 drug overdose deaths occurred in the US during a 12-month period ending in April 2021. Opioids were involved in 75% of these related deaths. Opioid Use Disorder (OUD) is a constantly evolving public health crisis with potentially lethal consequences. In 2017, 900 adolescents began to misuse opioids every day. Nearly 10% of high school seniors reported using opioids nonmedically. Additionally, the incidence for hospitalizations for adolescents among children 1-19 years of age increased nearly 2-fold from 1997 to 2012. This data emphasizes the dangers associated with the increasing accessibility of pharmaceutical and non-pharmaceutical opioids, particularly for adolescents. All three of the currently FDA approved medications for OUD have shown clear efficacy in decreasing all-cause mortality in adults. It is proposed that the same effects should be seen in adolescents but limited data is present. A recent study analyzed buprenorphine and naltrexone treatment amongst OUD in adolescents between 2001-2014; only 1 in 4 youth received any medication therapy within six months of diagnosis. Adolescents under 16 were the most likely to receive medications. However, even adolescents aged 17, for whom buprenorphine is FDA approved for, were less likely to receive therapy than adults over 18 years of age. The following case report aims to demonstrate how subcutaneous extended release buprenorphine treatment can be initiated effectively as an outpatient in an adolescent with OUD. It is critical that clinicians work to expand access to pharmacotherapy for adolescents struggling with OUD to ensure proper management and reduction of opioid-related overdoses.