Intravenous Formulation Research Articles

Exposure–efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn’s disease and ulcerative colitis

ABSTRACT Background and aims This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure−efficacy of vedolizumab intravenous (IV) and subcutaneous (SC). Methods A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (Cav,ss, Ctrough,ss) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score ≤ 2 points and no individual subscore > 1 point (UC), and CD activity index score ≤ 150 points (CD). Results Data were from 1968 patients (GEMINI 1 [n = 334], VISIBLE 1 [n = 216], GEMINI 2 [n = 1009], VISIBLE 2 [n = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted Cav,ss for IV-Q8W and SC-Q2W was similar in UC and CD. Cav,ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. Ctrough,ss values from IV and SC aligned well with pooled observed Ctrough by treatment group in UC and CD. Cav,ss was equivalent for SC and IV. For UC and CD, efficacy rates were greater in patients in the highest quartiles of vedolizumab exposure for both formulations. Conclusion Exposure−efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.

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.

Clinical usefulness of nebulized dexmedetomidine for conscious sedation in daycare flexible bronchoscopy in Southern India.

Sedative agents used in bronchoscopy require trained personnel to administer and monitor the patient. This increases the procedure cost, duration, and inpatient stay. Inhalational administration of sedative agents can be a practical solution to the issue. Dexmedetomidine in the inhalational form could give results similar to the intravenous form without significant adverse events. The study is prospective, randomized, and double-blinded study. Patients needing bronchoscopy were randomized to receive the nebulized form of either dexmedetomidine or saline (0.9%) before bronchoscopy. The study parameters are assessed and recorded before, during, and after bronchoscopy. Data collected are analyzed using the SPSS software. The side effects limit using commonly administered sedation agents in bronchoscopy, such as midazolam, fentanyl, and dexmedetomidine. The nebulized dexmedetomidine is safe with proven efficacy when compared to the placebo. Proceduralist-administered conscious sedation reduces the overall cost and shortens inpatient stays. Attenuation of hemodynamic parameters by dexmedetomidine could be an advantage for the physician in reducing an untoward cardiac event. Dexmedetomidine in the nebulized form improves the comfort of patients during the procedure. It blunts the pressure response during bronchoscopy and could be a safer and cost-effective agent in its nebulized form for conscious sedation in bronchoscopy. The study is approved by the institutional ethics committee (IEC KMC MLR 10-2021-310).

Doporučení Pracovní skupiny pro idiopatické střevní záněty pro diagnostiku Crohnovy choroby

Background and aims: Recently, the first subcutaneous infliximab (IFX), CTP-13, was approved in the indication of IBD. Pivotal study established noninferiority of subcutaneous infliximab to intravenous formulation in terms of efficacy, with no unexpected safety signals observed. The aims of the study were to evaluate persistency of treatment, pharmacokinetics and safety following a switch from intravenous to subcutaneous infliximab treatment. Methods: This retrospective, single-centre cohort study, recruited all Crohn’s disease (CD) and ulcerative colitis (UC) patients who transitioned from intravenous to subcutaneous IFX between September 2022 and September 2023. Clinical disease activity according to HBI and pMayo, sIBDQ, faecal calprotectin, drug persistence, safety and pharmacokinetics were evaluated at week 24 and 56 after the switch to subcutaneous infliximab. Results: A number of 107 patients was included (63 CD and 44 UC). Quality of life and clinical disease activity scores remained unchanged both in CD and UC. Faecal calprotectin decreased significantly in CD but not in UC. Patients that had been on standard compared to intensified IV infliximab dosing displayed similar outcomes on standard SC dosing. No serious adverse events occurred. Transient local injection reactions were experienced by 4.7% of patients. Median infliximab trough levels significantly increased after the switch to subcutaneous formulation. Conclusion: The switch from intravenous to subcutaneous infliximab is a safe and effective option for the treatment of inflammatory bowel diseases including those with active disease and/ or on intensified intravenous infliximab regime.

MODIFIED GENERAL ANESTHESIA FOR ELECTIVE CESAREAN SECTION

Introduction: The general anesthesia for elective caesarean section is used when there are contraindications to subarachnoid anesthesia, with a total frequency up to 20%. The medical community does not have a single unified algorithm of general anesthesia for this type of surgery. The main disadvantages of the general anaesthesia for caesarean section are a high percentage of the accidental preservation of the patient's consciousness during the operation (1:670) and a pronounced stress reaction to the surgical trauma. Purpose: To compare the «routine» technique of total intravenous anesthesia with artificial lungs ventilation for elective cesarean section and the modified general anesthesia with adjuvants addition. Materials and methods: Our study is based on an examination of 60 patients. All patients were randomly divided into 2 groups. The first group is a «routine» method of general anesthesia, the second group is modified general anesthesia with adjuvants addition. Intravenous forms of medical drugs were used as adjuvants: paracetamol (1000 mg), clonidine (100 μg), 30 minutes before surgery. Perioperative monitoring and treatment were based on the recommendations of the American Association of Anesthesiologists, the bispectral index and determination of the stress-induced substances (glucose, cortisol) blood levels were added. The newborns were evaluated with the Apgar scale and umbilical venous blood gas analysis was carried out. The two-sided Student's t-test was used for statistical data processing (p value = 0.001; Student's t-test < -3.466 and > 3.466). Results: There was no statistically significant difference in mean initial indicators between the two groups. The obtained results demonstrated the presence of statistically significant differences between the two groups: the mean blood pressure in a period after the trachea intubation/beginning of the surgery (t = 24.3); the mean blood pressure in a period of the newborn extraction (t = 25.5); the heart rate in a period after the trachea intubation/beginning of the surgery (t = 11.7); the heart rate in a period of the newborn extraction (t = 21.3); the bispectral index in a period after the trachea intubation/beginning of the surgery (t = 4); the bispectral index in a period of the newborn extraction (t = 8.2); assessment of newborns according to the Apgar scale at 1 minute (t = –4.5); pH of the umbilical venous blood (t = –5.44); PCO2 of the umbilical venous blood (t = 4.8); PO2 of the umbilical venous blood (t = –7.6); the blood glucose level in a period of the newborn extraction (t = 10.9); the plasma cortisol level in a period of the newborn extraction (t = 25.4). Conclusions: In view of the obtained results, modified general anesthesia with the adjuvants addition (clonidine, acetaminophen) in a period before the birth of a child during elective cesarean section has reasonable (statistically significant) advantages over the «routine» method of general anesthesia.

A study to evaluate patient benefit/risk preferences for treatment of metastatic prostate cancer (mPC) in Hong Kong: A discrete choice experiment.

104 Background: The patient’s preference for treatment is dynamic across different cultures and at various stages of cancer. Yet little is known regarding their priorities in making treatment decisions. The study's primary objective is to examine the preference weightings in terms of risk/ benefit attributes of therapy in metastatic prostate cancer (mPC) patients in both the hormone-sensitive (mHSPC) and castration-resistant (mCRPC) settings. Methods: This is a non-interventional cross-sectional survey study. A discrete choice experiment was used to assess their priorities on treatment options. 300 consecutive patients with mPC (200 mHSPC and 100 mCRPC) diagnosed within 5 years were recruited from the specialty clinics of our hospital from Feb 2023 to Jul 2023. A facilitated group interview session of 5 patients was conducted to evaluate the importance and relevance of potential attributes selected from the literature search. Five attributes were adopted, and each has 3 levels compromised between real-life rates and expectations of patients from the interview session. Patients were randomized into 2 blocks by recruitment sequence and chose 1 medication profile out of 2 throughout the 9 questions in each block of the questionnaire. A mixed logit model was used for data analysis. Results: Median age was 75 (IQR:71-81). One hundred and seventy (56.7%) had no income, and 245 (81.7%) claimed to take care of themselves. The mean maximum amount affordable for treatment was US$20,456 (SD:43,568), and 160 (53.3%) said they would not consider further treatment if the cost exceeded their affordability. Compared to intravenous formulation, oral medication once/day had a non-statistically significant favorable preference (0.06 p:0.272), and oral medication twice/day had a negative statistically significant preference (-0.20 p:0.040). The percentage of retained self-care ability (4.37 p<0.001) and percentage of extension in life expectancy (2.83 p<0.001) had a statistically significant favorable preference. In contrast, the chance of adverse effects leading to complicated medication treatment or hospitalization (-6.97, p<0.001) and treatment cost (in HK$ million) (-3.14 p<0.001) had a negative statistically significant preference. The mCPRC group was more sensitive to changes in treatment cost (-3.61 vs. -2.97), percentage of extension in life expectancy (3.47 vs. 2.55) and the chance of adverse effects (-7.55 vs -6.80) than the mHSPC group. Those who could afford treatment were more sensitive to the percentage of retained self-care ability (4.89 vs. 4.02) and the chance of adverse effects (-7.57 vs -6.70) than those who could not. Conclusions: The chance of adverse effects took the largest weighting in treatment decisions, followed by the percentage of retained self-care ability.

THE EFFECT OF CEFIXIME IN TREATING RESPIRATORY TRACT AND URINARY TRACT INFECTIONS IN CHILDREN

Third generation cephalosporins are commonly used for the treatment of diverse infections in children. Cefixime is an oral third-generation cephalosporin with a broad-spectrumantibacterial activity and a relatively long elimination half-life. It is available in oral, intravenous, and intramuscular forms. It is effective against certain bacteria, such as Streptococci, Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophiles influenzae, and Gram-negative bacilli. However, it is poorly active against Staphylococcus aureus, Coagulase-negative Staphylococci, and Enterococci. Clinical trials have shown that cefixime is comparable to amoxicillin and cefaclor in treating acute otitis media in children caused by various organisms, including Streptococcus pneumoniae. It is more potent than other cephalosporins against Enterobacteriaceae but less activeagainst ciprofloxacin. The recommended dosage for children is 8 mg/kg/day orally, once daily or in two divided doses and the most prominent side effect is diarrhea, which occurs in up to16% of children. Cefixime is a safe and effective for treating upper respiratory tract infections and acute otitis media. However, there is insufficient evidence regarding its efficacy in treating sinusitis and lower respiratory tract infections in children as its antimicrobial spectrum does cover the bacteria commonly associated with these infections. Due to its partial excretion through the kidneys, cefixime is frequently used to treat urinary tract infections in children.

P674 Real-world experiences of switching to subcutaneous formulation in IBD patients on maintenance vedolizumab treatment

Abstract Background Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking. Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort. Methods In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA < 1), and biochemical remission (BR, 5 mg/l > CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels. Results In total, 37 IBD patients were followed (Table 1., 15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7 % were in CSFR and 60 % in BR, while in UC group 63.6 % were in CSFR and 68.2 % in BR (p = 0.55 and p = 0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ± 6.9 to 30.6 ± 17.8 ug/mL, p = 0.047; UC: 13.6 ± 13.8 to 33.6 ± 17.6 ug/mL, p = 0.001, Figure 1.), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject. Conclusion Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.

P921 Maintenance of clinical, biochemical and transmural remission in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximab

Abstract Background Subcutaneous (SC) infliximab (IFX) effectively maintains biochemical, clinical and endoscopic remission in inflammatory bowel disease (IBD) with a comparable safety profile to intravenous (IV) formulation. Transmural healing is considered a desirable long-term treatment endpoint in IBD, especially in Crohn’s disease (CD). Whether switching from intravenous to SC-IFX effectively maintains transmural remission in IBD is still unknown. Methods This is a preliminary report from a prospective multicentre cohort study on IBD patients in clinical and endoscopic remission on IV-IFX treatment switched to SC-IFX. Enrolled patients were followed-up for 12 months, with fecal calprotectin (FC), C-reactive protein (CRP), infliximab trough levels and anti-drug antibodies (ADAs) measured at baseline, at 3, 6 and 12 months. Intestinal ultrasound (IUS) was performed at baseline and every six months. At month 12 a full colonoscopy was performed for mucosal healing assessment. Remission rates and safety profile were subsequently recorded. T-Test and ANOVA for mean comparisons and Kaplan-Meier estimates were used for survival curves. Results 43 IBD patients (69% males) were enrolled, 58% with CD, of whom 52% reported a history of perianal disease. Median disease duration and IFX therapy were 6 (IQR 3-12) and 5 (IQR 2-9) years, respectively. During a median follow-up of 311 (range 122-489) days, clinical remission rate was 98% (Harvey-Bradshaw Index <5 and Mayo score <2). No reactivation of perianal disease was reported. FC and CRP remained stable at each time point (p> 0.05). The median baseline infliximab level was 10.02 ( range 0.1- 41.84) ug/ml. Undetectable infliximab levels (<1 ug/ml) and positive ADAs were found in 6 and 14 patients, respectively; at 3 months, a significant increase in infliximab levels (mean increase 27.5 ng/ml; ± 12.5 SD; p< 0.001) and a progressive decrease of ADAs titer were observed, despite unchanged SC-IFX dose. At baseline, all patients had normal bowel wall thickness (i.e. ileum ≤ 3mm, colon≤4 mm) and a Limberg score ≤1at IUS; reactive lymphadenopathies were reported in 5 patients and a mild abdominal effusion in 1. No significant changes were shown during follow-up. Mild endoscopic activity was found in 2 out 30 patients who performed follow-up endoscopy. Regarding safety profile 12 mild infectious events, 2 mild cutaneous injection site reaction and 1 non-IBD related hospital admission were observed. Conclusion Switching from IV to SC infliximab in a selected cohort of IBD patients confirmed to be safe and effective in maintaining clinical, biochemical, and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment in this subset of patients.

P809 VARIETY BEACH: Real-world treatment patterns for vedolizumab intravenous and subcutaneous maintenance dosing observed over 1 year in studies from Belgium, Austria and Switzerland

Abstract Background Vedolizumab (VDZ) is approved for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) as intravenous (IV) or subcutaneous (SC) formulations. Real-world data on VDZ treatment patterns in patients (pts) with inflammatory bowel disease (IBD) comparing VDZ IV or SC maintenance are still scarce. Methods Three prospective, non-interventional, observational studies following an umbrella protocol enrolled pts in Belgium (NCT04959851), Austria (NCT04890262) and Switzerland (NCT04989907) from Aug 2021 to Jun 2022. Adults initiating VDZ IV induction per the product label or continuing VDZ IV maintenance with the option to switch to SC administration, were eligible. The primary endpoint was VDZ treatment persistence at 1 year. Administration route, dosing frequency, reasons for regimen change and safety endpoints were also assessed. Non- responder imputation was applied for pts discontinuing treatment, discontinuing the study or lost to follow-up. A descriptive analysis was performed. Results Of 377 pts enrolled, 373 (UC=218, CD=155) were included in this interim analysis. At enrolment, 287 (77%) (UC=159, CD=128) already received VDZ IV maintenance for median 2.8 (0–12.6) years and 86 (23%) (UC=59, CD=27) started VDZ induction (baseline pt characteristics summarized in Table 1). For pts enrolled on VDZ IV maintenance, 12 discontinued vedolizumab, 34 discontinued the study and 14 were lost to follow-up; resulting in a VDZ persistence rate at 1 year of 79% (227/287). Of pts in this cohort persistent on VDZ at 1 year (n=227; UC=124, CD=103), 39% (88/227) switched from VDZ IV maintenance to SC during the study. For pts initiating VDZ induction, 10 discontinued VDZ, 16 discontinued the study and 3 were lost to follow-up; resulting in a VDZ treatment persistence of 66% (57/86). Of pts from this cohort persistent on VDZ at 1 year (n=57; UC=43, CD=14), 56% (32/57) switched to VDZ SC during the study (Figure 1). Overall, the most common reasons for administration route changes were pt decision 98/161 (61%; UC=56%, CD=67%), end of induction (planned switch: 10%; UC=14%, CD=5%) and disease adequately controlled (6%; UC=7%, CD=3%). Adverse events (AEs) occurred in 48 pts (13%) (UC=20, CD=28) and serious AEs in 6 pts (2%) (UC=3: Budd-Chiari syndrome, death cause unknown, UC worsening; CD=3: bronchopneumonia, gastroenteritis, recurrent urinary tract infection). Conclusion Real-world data from prospective observational studies in Belgium, Austria and Switzerland reported high persistence of VDZ IV and SC maintenance treatment over 1 year. Decisions on route of administration change were most frequently driven by patients. Safety results were consistent with the known safety profile of VDZ.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

P893 Transition from intravenous to subcutaneous infliximab: effectiveness in a cohort of patients with inflammatory bowel disease

Abstract Background Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option. This study aims to evaluate evaluate the success of infliximab subcutaneous administration after switching from intravenous administration in IBD patients. Methods The transition from IV to SC administration was proposed to 60 IBD patients in clinical remission. Data on medical history and laboratory tests were collected from electronic health records. Moreover, patients filled a paper questionnaire 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE). Results Overall 60 patients were enrolled for switching from IV to SC therapy. Most of patients (>80%) did not experience any difficulties in handling the device and respected the correct time-table of administration. The switch was a complete success in 50 out of 60 patients (83.3%). Ten patients stopped subcutaneous formulation: five of these switched back to intravenous formulation for adverse event or patient’s preference, four swap or swop to other therapy and one withdraw from biologic. No predictor of loss of response was found at multivariate analysis. Faecal calprotectin and C-reactive protein values significantly improve after the switch at 3, 6 and 12 months (p= 0.03, p= 0.004, p = 0.01 and p= 0.06, p= 0.001, p= 0.007 respectively). About 16.7 % of patients had at least one side effect after switching. Local pain and swelling at site of injection were the most common AEs. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized. Conclusion Effectiveness of switching from intravenous to subcutaneous infliximab administration in IBD patients is confirmed in our real world cohort of patients.

P805 The persistence of subcutaneous infliximab is equivalent to intravenous form in patients with inflammatory bowel diseases

Abstract Background Switching from intravenous (IV) infliximab to subcutaneous (SC) is a new tool in treating patients with inflammatory bowel disease (IBD). This study aimed to evaluate the persistence and tolerance of SC IFX compared to IV IFX and to study outcomes of patients switched back to IV in a real-life patient cohort. Methods We conducted a retrospective monocentric study involving consecutive patients with IBD treated with maintenance IV IFX. The switch to SC was offered to patients in clinical remission receiving an IFX IV dose ≤ 10mg/kg every ≥ 6 weeks, and with a favorable patient profile (good adherence to IFX IV treatment, no decompensated psychiatric condition). Two groups were compared: a "switched" group receiving SC and a control group remaining on IV IFX due to an unfavorable patient profile or refusal of the switch. Results Among 360 consecutive patients treated by IV IFX, 282 were switched to SC and 78 remained on IV (44 due to refusal and 34 with an unfavorable profile). Both groups were similar in age, sex, and disease type and location; IV IFX dosage and frequency were higher in the IV group. With a median follow-up of 59 (46-67) weeks, SC IFX was discontinued in 28/282 (10%) patients (10 due to relapse, 10 by patient decision, and 8 due to intolerance), whereas it was stopped in 1/78 (1%) IV IFX patient for intolerance (p=0.01). Among the 28 who discontinued SC IFX, 27 reverted to IV, with 4 (1% of the switch group) permanently stopping IFX. Overall, persistence rates for IFX, irrespective of administration route, were comparable between the two groups at 52 weeks: 99% (96-100%) for IV versus 99% (98-100%) for SC (p=0.60). Adverse events were more frequent in the switched group than the control group (10% versus 3%, p=0.03). Primarily, this involved psoriasiform lesions in 9 patients; 4 patients reported an injection site reaction. The proportion of side effects leading to IFX discontinuation or hospitalization was identical in both groups (1 patient, 2%). Conclusion In a real-life cohort, switching from IV to SC IFX does not alter treatment persistence. In cases of poor tolerance to SC IFX, IV IFX re-initiation is effective. Switching to SC IFX is a therapeutic option for patients in remission on IV IFX.

P-17 Hypophosphatemia related to intravenous iron therapy: A case report

Abstract Introduction Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia. Intravenous iron formulations such as ferric carboxymaltose allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important complication of ferric carboxymaltose is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). In this case, we aimed to present our patient with this rare side effect of intravenous iron replacement. Clinical Case A 40-year-old female patient who has no chronic systemic disease was admitted to our endocrinology service for fatigue and weakness. In the patient's history, it was learned that she had been treated with 2500 mg intravenous iron replacement (ferric carboxymaltose) for iron deficiency anaemia in the last month. In the laboratory tests; serum phosphorus 1.05 mg/dl (normal 2.5-4.5 mg/dl), corrected calcium 8.45 mg/dl (normal 8.4-10.2 mg/dl), 25-OH vitamin D 31.4 µg/L (normal >30 µg/L), parathormone 83.2 pg/ml (normal 15-65 ng/ml), alkaline phosphatase 63 U/L (normal 35-105 U/L). Fractional excretion of phosphate (FePO4) confirmed renal phosphate wasting (FePO4: 28.6%; normal <5%). Urinary protein and glucose were negative. FGF23 measured 71 pg/ml (normal <59 pg/mL). Intravenous iron-induced hypophosphataemia was suspected. After initiation of oral phosphate and 1,25-dihydroxyvitamin D3 supplementation, serum phosphate rose to reference range (Figure 1). The patient was taken to outpatient follow-up. Conclusion Physicians should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses.Figure 1.Patient phosphorus data during follow-up

Extremely rare complication in high-risk newborn on long-term parenteral nutrition and large stool losses through ileostomy.

To analyse postnatal characteristics, clinical and laboratory findings, results of investigations in the newborn (25 gestational weeks; Apgar score: 6/9 points; born per caesarean section; birth weight: 600 g; birth length: 31 cm; head circumference: 21 cm) from the first high-risk pregnancy with acquired form of acrodermatitis enteropathica. After summarizing the clinical picture with laboratory findings, we analysed the components of parenteral nutrition with regard to the deficiency of trace elements and vitamins. The zinc depletion dominated. The diagnosis is clinical, based on the presence of atypical clinical picture together with alow serum zinc concentration. Standard preparations with elementary elements do not sufficiently cover the daily needs of children, other possibilities of supplementation in intravenous form are not available. It is necessary to supplement zinc in premature children, in children with high losses of zinc (with diarrhoea, in patients with astoma, in patients with severe skin disease) (Fig. 4, Ref. 15).

Take vedolizumab home: transition from intravenous to subcutaneous treatment.

In 2020, the European Medicines Agency approved subcutaneous (SC) vedolizumab (VDZ) for the maintenance treatment of adult patients with moderate to severe inflammatory bowel disease (IBD). This article reviews the efficacy, safety, persistence, pharmacology, patient satisfaction, and economic implications of transitioning to SC VDZ treatment and explores whether SC formulations can be recommended by the same guidelines as intravenous (IV) formulations. Clinical trials and real-world evidence indicate that transitioning from IV to SC VDZ in patients with IBD maintains clinical, biochemical, and patient-reported clinical remission and is well-tolerated, with no new safety issues identified, except for injection site reactions. Moreover, SC VDZ has an exposure-response relationship and low immunogenicity, is economical, and provides a high level of patient satisfaction. Owing to these advantages, transitioning may be advisable. In the future, more studies are needed to clarify the exact role of SC VDZ in IBD treatment, including optimization and transitioning strategies and individualized treatments based on baseline characteristics.

Diagnosis and treatment of iron deficiency anemia

The causes of iron deficiency anemia include blood loss, increased demand, insufficient dietary intake, and disorders affecting iron absorption. In certain circumstances, atrophic gastritis, either autoimmune or due to Helicobacter pylori infection, may contribute. On very rare occasions, iron-refractory iron deficiency anemia can develop as a consequence of TMPRSS6 mutations. Iron deficiency anemia is diagnosed by identification of microcytic hypochromic anemia with low serum ferritin levels. In cases of chronic disorders such as chronic kidney disease, chronic heart failure, and chronic inflammatory disorders, the diagnosis may also incorporate transferrin saturation. Treatment of underlying diseases is recommended along with iron supplementation. While oral iron supplements are the first choice, intravenous iron may be considered when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. Recently, high-dose intravenous iron formulations became available in Japan, but their use requires caution due to potential risks of allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage. Notably, the benefits of high-dose intravenous iron for patients with heart failure and iron deficiency are recognized in the field of cardiology. This article provides an overview, incorporating recent developments in the field of iron deficiency anemia.

Outcomes of treatment cessation after switching to subcutaneous vedolizumab treatment in inflammatory bowel diseases.

The usability of subcutaneous vedolizumab (s.c. VDZ) treatment in inflammatory bowel diseases (IBD; ulcerative colitis (UC), Crohn's disease (CD)) has been proven via clinical trials while real-world data collection is ongoing. Our study evaluates the effectiveness, safety, patients' preferences, and psychological factors associated with s.c. VDZ treatment, after switching from intravenous (i.v.) formulation. Prospective, multicenter cohort study including IBD patients switching from i.v. VDZ to s.c. treatment and were evaluated over 52 weeks. Serum VDZ levels and C-reactive protein (CRP) were measured at the baseline and w52. At w12, a questionnaire on the patient's satisfaction and psychological characteristics was administered. The primary outcome was the drug persistence rate (cessation was due to loss of response (LOR), adverse events, patient request, and other causes) at w52, while the secondary outcomes were the changes in the clinical corticosteroid-free remission (CSFR) and biochemical remission (BR; CRP ⩽ 5 mg/L) rates, safety issues, serum drug levels, patients' preferences, and psychological features. In total, 70 IBD patients were evaluated (32 CD patients, 38 UC patients; male/female ratio: 41.4%; median age: 43.2 years). In the CD group, 81.3% were in CSFR and 65.6% were in BR, while in the UC group, 71.7% were in CSFR and 69.4% were in BR. Overall, 17.1% of the patients ceased s.c. VDZ treatment after a median of 26.2 (interquartile range 20-47) weeks. LOR was registered in 3/12 ceased patients. In addition, CSFR and BR rates were stable, while serum VDZ levels increased by w52 (p < 0.001). The transition from i.v. to s.c. VDZ treatment was effective, the overall persistence rate was associated with high serum drug levels, and no novel safety issues were reported. Although s.c. administration after induction can save resources, some patients still insisted on i.v. VDZ treatment, due to its proven formulation.

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.

Investigating the Hydrodynamics of Intravenous Drug Infusions

One of the most common reported adverse events for intravenous (IV) infusions are infusion site reactions, ranging from redness and pain at the site of infusion to thrombophlebitis. The connection between drug infusion and what drives these adverse events is not well understood. To aid in understanding these phenomena, it is crucial to accurately characterize the evolving hemodynamic environment of the infusion site when developing new intravenous formulations, as too rapid dilution may cause precipitation in the vein, while too little dilution might contribute to phlebitis. In this study, a Large-Eddy Simulation (LES) turbulence modeling inside a Computational Fluid Dynamics (CFD) framework has been used to simulate the flow and mixing characteristics of an infusion entering the bloodstream. This work represents the first such study reporting transient flow fields for intravenous infusions using LES CFD simulations with a realistic non-Newtonian blood model. The output of the CFD model closely resembled the flow and mixing patterns generated in benchtop tests for infusions into a blood analogue and water as the venous fluid across a wide range of flow rates. These models were then investigated further to compare how changes to the fluid rheology model, needle orientation and needle position within the vein resulted in altered mixing regimes at different flow rates.