Reasons For Discontinuation Research Articles

Low prevalence of methotrexate intolerance in rheumatoid arthritis: a South African study.

Methotrexate (MTX) is the first line therapy for rheumatoid arthritis (RA), and despite its widespread use, there is very little information about MTX intolerance in sub-Saharan Africa. The aim of this study was to assess the prevalence of MTX intolerance and other reasons for stopping MTX in RA in South Africa. A retrospective chart review of all RA patients seen at Inkosi Albert Luthuli Hospital in Durban from 2009 to 2019 was undertaken. We included patients who received MTX for at least three months. All patients received folic acid supplements. Patients who discontinued MTX were categorized as having either MTX related toxicity or other reasons. A total of 695 patients were identified with a female to male ratio of 7:1. The mean age was 57.9 (± 13.3) years, and median duration of MTX use was 67.0 (39.0-106.0) months. Most of the patients were African Blacks (61.2%), and Indians (32.8%). There were 83 (11.9%) patients who stopped MTX, and it was successfully reintroduced in 25 of them. Thus, 58 (8.3%) patients discontinued therapy, 33 (4.7%) due to intolerance and 25 (3.6%) due to factors other than adverse effects. The commonest causes of MTX intolerance were respiratory, gastrointestinal and haematological. The other reasons for discontinuation included co-morbidities and pregnancy related concerns. The low prevalence of MTX intolerance in a multiethnic population in this single centre study, confirms the value of MTX as anchor therapy, especially in resource constrained settings. Key Points • We report a low and similar prevalence of methotrexate intolerance in a large population of African Blacks and Indians with RA in sub-Saharan Africa. • Even though there was heterogeneity among other studies, our review indicates that MTX was tolerated better in our patients compared to patients in Europe and the United States of America.

First line atezolizumab + bevacizumab (atezo/bev) or durvalumab ± tremelimumab (durva±treme) in unresectable hepatocellular carcinoma (HCC): A real world, multi-institutional retrospective cohort study.

532 Background: HCC accounts for 80% of primary liver cancers, and worldwide, is the third common cause of cancer-related death. Two FDA approved 1st line systemic treatment options include atezo/bev and durva ± treme. Herein we report outcomes of these regimens in the 1st line setting via a real-world, multi-institutional retrospective cohort study. Methods: We reviewed clinical outcomes of patients (pts) who initiated 1st line atezo/bev or durva ± treme for unresectable HCC between March 2017 and February 2024, across 5 institutions (Mayo Clinic, University of Alabama, Cedars-Sinai Medical Center, University Hospitals Seidman Cancer Center and University of Michigan). Time to treatment failure (TTF) and overall survival (OS) were analyzed using the Kaplan-Meier method. Best (objective) response was tabulated. Multivariable analyses were performed using Cox models and logistic regression for time-to-event and binary outcomes, respectively, while adjusting for age, sex, race, HCC etiology, Child-Pugh class, and ALBI grade. Results: A total of 433 HCC pts were included; atezo/bev (336), durva ± treme (97). Median age at the start of therapy was 68 years; 77% were male, 82% were Caucasian. Etiologies of HCC were viral hepatitis (38%), MASLD (20%), alcohol (10%), non-viral multifactorial (10%), or unknown (22%). Pts receiving durva ± treme were less likely to have cirrhosis (11% vs. 28%, p<0.01) but similar in terms of macrovascular invasion (63% vs. 58%, p=0.35) compared to pts receiving atezo/bev. Reasons for treatment discontinuation were similar between the two groups, with the most common being disease progression - atezo/bev (56%) and durva ± treme (47%). The differences in clinical outcomes were not statistically significantly and remained consistent after multivariable adjustment. (Table, atezo/bev as the reference group). Outcomes were significantly different between Child-Pugh classes (CP: A,B,C) respectively, OS: 19.0 m, 6.4 m, 1.9 m (p<0.001); TTF: 6.1 m, 2.7 m, 1.3 m (p<0.001). Conclusions: In this real-world retrospective cohort study of unresectable HCC, the differences in overall survival, objective response, and time to treatment failure were not statistically significant between atezo/bev and durva ± treme in the 1st line setting. Outcome Atezo/bev Durva±treme Univariate p-value Multivariable adjusted hazard ratio (95% CI) Multivariable adjusted odds ratio (95% CI) Overall Survival, Median (month) 14.0 14.6 0.77 0.78 (0.54-1.14) --- Time to Treatment Failure, Median (month) 4.9 4.1 0.71 0.95 (0.72-1.26) --- Objective response, % 26.3% 21.1% 0.31 --- 0.78 (0.43-1.39)

CLINICAL EXERCISE PHYSIOLOGISTS IN THE INPATIENT SETTING – A CASE STUDY

https://youtu.be/i0pv5V6NKxM INTRODUCTION Preservation of functional capacity for patients admitted to the cardiovascular intensive care unit (CVICU) relies heavily on interventions prescribed by physical therapy. Traditional interventions are bed/chair exercises utilizing only body weight and ambulation around the unit. In this case, the clinical exercise physiologist (CEP) sought to push this standard of care to prepare a subject implanted with a BiVACOR total artificial heart (TAH) for orthotopic heart transplantation (OHT). This serves to present the methods in doing so and the need to further implement the role of clinical exercise physiologists in the inpatient setting. CASE PRESENTATION A 51-year-old male with history of chronic nonischemic cardiomyopathy, hypertension, diabetes mellitus, hyperlipidemia, and obesity presented to the hospital for right heart catheterization (RHC) in the setting of increased heart failure symptoms. Results of RHC led to admission and listing as UNOS status 4 for OHT. Hospital course was complicated by hypotension, ventricular tachycardia, and chronic kidney disease. Cardiothoracic surgery determined the need for mechanical circulatory support, a TAH as bridge to transplant. The patient elected to undergo implantation of BiVACOR, a TAH geared towards individuals with biventricular or univentricular heart failure where left ventricular assist device is not recommended. The patient is part of the BiVACOR Early Feasibility Trial in humans, approved by the FDA – he was the third human implant and would remain in hospital until OHT. The goal of the multi-disciplinary team was to preserve functional capacity during admission. MANAGEMENT Before implant, the patient’s 6-minute walk test (6MWT) distance was 320 meters, 2.52 METs. Post-implant in the ICU, the patient walked 1,800 feet 4 times per day. His 6MWT distance 13 days post-implant was 411 meters, 2.95 METs. By day 22 post-implant the patient progressed to recumbent bike cycling intervals. He was able to tolerate one 3-minutes interval and two 4-minutes intervals, split by 6-minutes rest intervals. His prescription was to cycle at 55-65 RPMs for 10-15 minutes three days per week with progression to 30 minutes continuously, 5-6 days per week. The patient was transplanted prior to completing any further sessions. During the cycling session, his blood lactate was measured at 5.2 mmol and hemoglobin 5.7 g/dL. His blood pressures remained stable, with normal responses to exercise, and pump flow increased from 8.9 L/min at rest to 12.5 L/min at peak exercise. Reported quadriceps muscle fatigue was the reason for session discontinuation. DISCUSSION Inpatient rehab goals of care should evolve to include various modalities of exercise that allow for more physiological adaptations, decreasing the impact of frailty and improving quality of life during admission. This patient’s case is an attestation to the growing need for exercise intervention prescribed by the CEP at all levels of care.

TAS102 in combination with oxaliplatin (TASOX) for refractory metastatic colorectal cancer.

189 Background: TAS102 (trifluridine/tipiracil hydrochloride) is approved for use alone or with bevacizumab in late line metastatic colorectal cancer (mCRC), with overall survival benefit in phase 3 trials (RECOURSE and SUNLIGHT). Oxaliplatin is frequently reintroduced after progression, resolution of limiting neuropathy, or disease recurrence post adjuvant therapy. In preclinical studies, oxaliplatin combined with TAS102 has shown synergism. We hypothesized TASOX may be an option for patients who have progressed/recurred after FOLFOX. Methods: We assessed safety and efficacy of TAS102 with oxaliplatin, enrolling patients with metastatic CRC progressed on ≥2 lines of therapy including 5FU, oxaliplatin and irinotecan. Patients with recurrence during or within 6 months of adjuvant chemotherapy were allowed. Exclusion: Prior TAS102 exposure, functional impairing peripheral neuropathy, ≥Grade 3 hypersensitivity to oxaliplatin, or uncontrollable grade 1-2 hypersensitivity to oxaliplatin. Treatment continued until disease progression or unacceptable toxicity. Patients received oxaliplatin 85 mg/m2 and TAS-102 35 mg/m2 bid days 1-5 every two weeks, and bevacizumab per MD choice. The primary endpoint was overall response rate (ORR) by RECIST (by independent radiologists). Secondary endpoints included disease control rate (DCR), safety and tolerability. Results: 54 patients enrolled; 53 received treatment on study and 48 had ≥1 disease assessment (median age 59, 58 % male, tumor RAS mutated 69%). Median time on study was 4 months (8 cycles; range 1-37 cycles). ORR was 6% (n=3), with average change in target lesions -45% (range -35 to -67%). 71% (n=34) had SD defined on study, with average change in target lesions -3% (range -29% to +20%). In those treated with bevacizumab (59%; n=28 ), 79% (n=22) had disease control vs. 75% (n=15). The most common reason for study discontinuation was progressive disease (23%, n=11). 68% (n=36) had a treatment-related adverse event (TRAE) ≥Grade 3 at any point during therapy. The most common G3 TRAEs were anemia 19% (n=10) and leukopenia 28% (n=15) at any time. Two (4%) developed grade 3 neuropathy. Conclusions: TASOX is effective as a 3rd line therapy for patients with mCRC. In our study, overall disease control rate was 77% with up to 19 months on study. Anemia and leukopenia are common but manageable. Bevacizumab did not seem to have as great an effect in our trial as observed in SUNLIGHT. Future studies would warrant TASOX in combination to bevacizumab in randomized trials in candidates for oxaliplatin retreatment. Clinical trial information: NCT02848079 .

The efficacy of anamorelin in gastrointestinal cancer with cancer cachexia: Single center experience.

815 Background: Cancer cachexia is a catabolic syndrome that causes weight loss and loss of appetite in cancer patients. Anamorelin (ANAM) is an oral drug approved in Japan to treat cancer cachexia by selectively activating ghrelin receptors. There is limited real-world data available on the efficacy of ANAM for patients with gastrointestinal cancer. We assessed its efficacy and identified associated clinical features. Methods: We retrospectively collected data from medical records and questionnaires on gastric and colorectal cancer patients who received ANAM between April 2021 and March 2023. We evaluated the change in body weight, appetite, and oral intake from the time of initiation of ANAM. We judged the responder who gained more than 0.5 kg in body weight, improved appetite, and increased oral intake, respectively. The association between clinical features and the responders was also assessed using multivariate logistic regression analysis. Results: 72 patients were included in this study. Characteristics of the patients: median age: 68 years old (range 38-85), male/female: 35/37, gastric/colorectal cancer: 39/33, PS 0-1/2 or more: 63/9, median body mass index (BMI): 18.0 kg/m 2 (range 12.3-27.9), number of prior chemotherapy regimens 1/2/3 or more: 17/22/33, ascites none/mild/moderate/severe: 42/19/7/4, median serum albumin levels (Alb): 3.2 g/dl (range 2.0-4.2). The median treatment duration of ANAM was 47.5 days (3-450 days). 57 patients (79.2%) continued ANAM for more than 3 weeks, and 9 patients for more than 12 weeks. The main reasons for discontinuation were progressive disease (39.7%), ineffective (12.7%), effective (11.1%) and adverse events of ANAM (11.1%). 33 patients (45.8%) gained weight, 41 patients (56.9%) improved appetite and 34 patients (47.2%) increased oral intake. There was a correlation found between BMI ＜ 18.0 kg/m 2 and the responders (OR 3.43, p = 0.041). Conclusions: In this study, 68.0% of patients who received ANAM for showed response, that is, gained body weight, or improved appetite, or increased oral intake. And these observations suggested that BMI was associated with effects of ANAM. Further studies involving more patients needed.

Phase II study of neoadjuvant FLOT and chemoradiation for trimodality therapy of esophageal/GEJ adenocarcinoma.

466 Background: Recent data support use of perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) chemotherapy over pre-operative chemoradiation (CRT) for patients with resectable esophageal/GEJ adenocarcinoma with limited studies evaluating combined FLOT/CRT. This prospective phase II study (NCT04028167) evaluated a neoadjuvant approach of FLOT followed by CRT for resectable esophageal/GEJ adenocarcinoma (EAC). Methods: Operable patients with cT1-2 N1-2 or cT3-4N any4 Nany non-metastatic EAC were eligible. Neoadjuvant treatment consisted of FLOT x 3 cycles followed by restaging PET and chemoradiation (41.4 Gy / 23 fractions to the primary site and regional lymphatics with weekly carboplatin/paclitaxel). Adjuvant nivolumab for non-pathologic complete response (pCR) was permitted. The primary endpoint was pCR rate among patients receiving the study regimen and undergoing resection, with secondary endpoints including disease free survival (DFS), overall survival (OS), toxicity, and correlative studies. DFS/OS was measured using the Kaplan Meier (KM) method. Interim results are presented after a planned safety analysis. Results: Since 4/2020, 23 patients with median age of 62 (range 40-73) have enrolled. cT3-4 and cN+ disease was present in 20/23 (87%) and 16/23 (70%) of patients, respectively. FLOT was completed by 21/23 patients (reasons for discontinuation included allergic reaction and G5 sepsis/endocarditis). All 21 patients initiating chemoradiation completed planned treatment and 17/21 underwent resection (2 refused surgery after achieving cCR, 1 died of cardiac arrest, 1 patient is awaiting surgery). A pCR was observed in 5/17 resected patients (29%), with pCR or near pCR observed in 9/17 (53%). The complete response rate (pCR + cCR for patients refusing surgery) was 7/19 (37%). Adjuvant nivolumab was administered in 9 patients. The median follow-up among all patients was 20 months with 2-year DFS and OS estimates of 61% and 73%. The regimen was tolerated with G3+ hematologic, G3+ gastrointestinal, and G3+ other toxicity observed in 39%, 13%, and 22% of patients, respectively. Conclusions: In a locoregionally advanced population, neoadjuvant sequential FLOT followed by CRT was well tolerated with encouraging DFS/OS and a high rate of complete response compared to prior studies. This hybrid platform may enhance both locoregional and distant control and is of interest for expanded evaluation. Clinical trial information: NCT04028167 .

Predictive factors for the efficacy of nal-IRI + 5FU/LV therapy in patients previously treated with conventional irinotecan.

737 Background: There were some reports that nal-IRI + 5FU/LV (NAPOLI) therapy was effective for patients with unresectable pancreatic cancer who had a history of treatment containing conventional irinotecan (IRI) though the others did not. We aimed to investigate the factors that contribute to the effectiveness of NAPOLI therapy for patients who have already received IRI-containing treatment. Methods: We retrospectively enrolled the consecutive patients who had previously treated with IRI-containing treatment and started NAPOLI therapy at our hospital between June 2020 and December 2022. We compared the patient backgrounds of patients who achieved CR, PR, or SD according to RECISTv1.1 (effective group) and those who did not (ineffective group). Continuous variables were divided into two groups by the median of the entire population, and factors contributing to the effectiveness of NAPOLI therapy were determined by logistic regression analysis. Results: The subjective were 52 patients. The reason for discontinuation of IRI-containing treatment was refractory and intolerant in 45 and 7 patients, respectively. The median age was 65 years. Twenty-three patients (44%) had ECOG PS of 0, and 41 patients (79%) had metastatic disease. The median albumin, CRP, CEA and CA 19-9 was 3.8 g/dL, 0.3 mg/dL, 8.5 ng/mL and 2082 U/mL, respectively. Twenty-one patients (40%) showed SD and they were allocated in the effective group whereas 31 patients were in the ineffective group. Of the 21 patients in the Effective Group, 16 patients(76%) were refractory, while of the 31 patients in the Ineffective Group, 29 patients (94%) were refractory. The factors contributing to disease control were PS of 0 (odds ratio, 5.79; 95% confidence interval, 1.34–25.0), CA 19-9 <1000 U/mL (odds ratio, 5.53; 95% confidence interval, 1.26–24.3), and Alb >3.8 g/dL (odds ratio, 5.19; 95% confidence interval, 1.14–23.7). Age, sex, disease stage, serum level of CRP, and CEA did not affect the effectiveness of NAPOLI therapy. Conclusions: Even in patients who have already received IRI treatment, the NAPOLI regimen is expected to be effective in patients with PS of 0, Alb >3.8 g/dL, and CA 19-9 <1000 U/mL.

Phase II study of neoadjuvant NALIRIFOX followed by chemoradiation with paclitaxel and carboplatin in locally advanced gastroesophageal cancer.

452 Background: We performed a single-arm phase II study of neoadjuvant NALIRIFOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients with locally advanced gastroesophageal (GE) cancer. Methods: Patients were enrolled on an NCI sponsored, prospective, single arm study (NCT04656041). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive GE junction or esophageal cancer, ECOG PS ≤1, age 18+, and life expectancy > 3 months. Exclusion criteria included: metastatic disease, prior chemotherapy or RT, or prior targeted therapy for diagnosis. Extensive LN disease beyond the surgical field (supraclavicular or para-aortic) was permitted if deemed feasible to be encompassed within a RT field. Laparoscopy was not required. Pts were treated with neoadjuvant NALIRIFOX x 4-8 cycles pending patient tolerance and physician discretion, restaging, CRT (50.4 Gy in 28 fractions) with concurrent C/T, restaging, followed by surgical resection. Dose reductions were at discretion of the treating physician. The primary study endpoint was the pathologic complete response rate following neoadjuvant treatment with NALIRIFOX and CRT with concurrent C/T. Major pathologic response (mPR) was defined as Tumor Regression Grade 0 and 1. Secondary endpoints included: 1) acute toxicity; 2) clinical response per RECIST criteria; 3) PFS and 4) OS. Results: From June 2021 to October 2023, 40 patients were enrolled. Median age was 64 (range: 47-82), and 31 patients were male (78%). All patients started NALIRIFOX, and the median number of NALIRIFOX received was 5 (range: 1-8). Reasons for discontinuation of NALIRIFOX were: physician discretion (n=29), subject withdrew from treatment (n=2), progressive disease (n=1), death (n=1). Rates of grade 3+ toxicity for overall, gastrointestinal, and hematologic attributed to NALIRIFOX were 55%, 35%, and 13% respectively. 35 patients started chemoRT (88%) and 33 patients completed chemoRT (83%). Rates of grade 3+ toxicity for overall, gastrointestinal, and hematologic attributed to chemoRT were 86%, 11%, and 9% respectively. Of 33 who completed chemoRT, two patients declined surgery (including 1 with clinical CR), and 31 (78%) patients went for surgical exploration. No patients were found with intraoperative metastases. Therefore, 31 (78%) patients underwent surgical resection. In total, 9 patients had pCR (29% in resected cohort, 23% in ITT cohort) and 15 had a major PR (48% in resected cohort, 38% in ITT cohort). In total, 10 (25% in ITT) patients had pCR or clinically CR at 1 year. Conclusions: Neoadjuvant NALIRIFOX followed by CRT is feasible with acceptable rates of treatment completion and grade 3+ toxicity. In our phase II trial, the rate of pCR is promising and further studies incorporating this regimen should be considered. Clinical trial information: NCT04656041 .

P-2307. Premature Discontinuation of Trimethoprim-Sulfamethoxazole Prophylaxis in Abdominal Transplant Recipients: A Deeper Dive

Abstract Background Trimethoprim-sulfamethoxazole (TS) prophylaxis can prevent Pneumocystis jirovecii (PCP) and other opportunistic infections (OIs), such as intestinal protozoa, Toxoplasma, Listeria, and Nocardia. We sought to assess the frequency, causative factors, and impact of early TS discontinuation in abdominal SOT recipients. Methods This is a single-center, retrospective cohort study of adult abdominal SOT recipients at Mayo Clinic Arizona between 1/1/2021 and 6/30/2023. Objectives included the rate and reasons behind early TS discontinuation and whether TS prophylaxis was reinitiated. Early discontinuation was defined as cessation of TS prophylaxis within 6 months post-transplant for ≥7 days. Secondary outcomes included median duration of therapy, alternative prophylactic agent utilized, and incidence of TS preventable OI. Patients were excluded if they had no TS ordered, died <180 days from transplant, or received a thoracic organ transplant. Results 942 abdominal SOT recipients were identified. Thus far 171 liver, 11 Kidney, and 29 liver/kidney have been reviewed and included in the current analysis. TS was discontinued early in 60 (28%) patients. Predominant reasons for discontinuation were hyperkalemia (45%), cytopenias (17%), and acute kidney injury (15%). Allergy was the indication for discontinuation in 1 patient. Median duration of TS before discontinuation was 39 days (IQR 66). TS was not resumed in 78% of cases. The predominant reason for non-resumption was alternative prophylaxis with no clear intent to rechallenge TS (70%). The main discontinuation reason had resolved in 70% that stopped due to cytopenias, 67% that stopped due to liver injury, and 96% that stopped due to hyperkalemia. Alternative prophylaxis included pentamidine (50%), dapsone (32%), atovaquone (5%), none (13%). No patients developed PCP or other TS preventable OI during 9-month follow-up post-SOT. Conclusion TS is discontinued prematurely in a significant number of SOT recipients and is often not resumed despite resolution of the offending cause. Given its proven track record in preventing several OIs in SOT recipients, providers should document reason(s) for TS discontinuation and consider resumption of TS after reasons for discontinuation resolve. Disclosures All Authors: No reported disclosures

Treatment of Insomnia by Zopiclone in Older Adults Hospitalized in a Geriatric Hospital: A Retrospective Study

Background Insomnia is a significant public health problem that can affect up to 50% of older adults. Pharmacological treatments are commonly used such as benzodiazepines (BZD) and related Z-drug zopiclone. Purpose The objective of this study was to investigate the use of zopiclone under real-life clinical conditions. Materials and Methods A retrospective review of older patients was conducted in a French geriatric hospital. The eligible participants included patients aged 65 years and older who had received zopiclone as a hypnotic. The presence of indication, the dosage and duration of zopiclone, the reevaluation of the treatment, the reason for discontinuation, and the combination with BZD were assessed. Results The study included 30 subjects (mean age 84.6 ± 9.3 years), 90% of whom received zopiclone 3.5 mg and 10% zopiclone 7.5 mg. In 60% of cases, no indication of insomnia was found. At discharge, more patients received a combination of zopiclone and BZD. The drug reassessment was initiated in only nine patients. Conclusion The treatment of insomnia with zopiclone is usually prescribed for long-term periods in older adults with less need for reevaluation. More long-term data on side effects and therapeutic efficacy are needed in routine clinical practice.

506. Week 26 Interim Analysis of Implementation and Delivery of Long-Acting Injectable Cabotegravir for PrEP in a Community Pharmacy Setting

Abstract Background For years, pharmacists have successfully managed oral PrEP therapy through collaborative agreements. The recent availability of long-acting PrEP injectables requires new strategic development for treatment delivery. We aim to demonstrate that a pharmacist-managed PrEP program using long-acting injectable cabotegravir (CAB-LA) in a community pharmacy setting is feasible, as measured by at least 50% of patients retained in care and acceptable to patients. Figure 1. Screening and Follow Up Methods This is a 26-week interim analysis of an observational, mixed methods study of 50 participants who have enrolled and been in care at Kelley-Ross Pharmacy in Seattle, Washington from June 1, 2023, to April 26, 2024. The protocol was approved by the institutional review board. Data was collected from both patient surveys and retrospective chart review by study investigators. Participants completed a baseline survey and benefits investigation for CAB-LA for PrEP after enrollment. Follow up surveys were collected at every visit, including early discontinuation. Feasibility outcomes include proportion of participants recruited and retained in PrEP care and adherence (Table 2). Acceptability outcome of patient satisfaction is measured through qualitative data generated from surveys, represented as a Likert scale quantified with variance applied (Figure 2).Table 1.Baseline Characteristics Results Fifty participants were enrolled in the study, 43 (86%) of who received an initial injection of CAB-LA. Thirty-five (81%) participants are retained in care through 26 weeks. Out of the 122 injections given, 115 (94%) were on time. Baseline participant satisfaction survey responses are detailed in Figure 2. There were no HIV seroconversions while in the study. Out of the 43 participants who received CAB-LA, eight discontinued prior to week 26 (Figure 1).Table 2.Outcomes Conclusion Our data show that a pharmacist-managed CAB-LA for PrEP program in a community pharmacy setting is feasible and acceptable. Patients who were started on CAB-LA for PrEP had a very low discontinuation rate at 26 weeks and expressed a high degree of satisfaction in patient surveys. Reasons for discontinuation are varied among participants. This interim analysis supports the implementation of a pharmacist-managed CAB-LA program in a community pharmacy setting.Figure 2.Baseline Survey Participant Barriers and Facilitators of CAB-LA for PrEP Likert scales quantified with variance applied. The point scale is as follows: 1- strongly disagree, 2- disagree, 3- neutral, 4- agree, 5, strongly agree. Participants completed baseline survey at the time of enrollment, prior to first CAB-LA injection. One participant did not complete the survey and was eliminated from the data set for the above parameters. Disclosures Elyse Tung, PharmD, BCACP, Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Honoraria|National HIV PrEP Curriculum: Advisor/Consultant|Viiv Healthcare Ltd.: Advisor/Consultant Peter Shalit, MD, PhD, Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria

P-582. Long-term effectiveness and tolerability of Dolutegravir/Lamivudine in Korea: 3 year follow up

Abstract Background Many studies have revealed the real-world effectiveness and tolerability of Dolutegravir/Lamivudine (DTG/3TC). However, most studies were conducted in Western countries, and data from Asian countries are still lacking; in particular, the results from long-term use have not been reported in Asian countries. As DTG/3TC has been introduced and is becoming increasingly widespread in Asia, it is necessary to investigate the maintenance rate, reasons for discontinuation, long-term effectiveness, and metabolic parameter changes. Methods We performed a retrospective cohort study with adult people with HIV treated with DTG/3TC specific combination at a tertiary hospital in Korea. Among them, those who were followed up for more than 36 months were included. Both treatment-naïve and those who switched from other antiretroviral therapies to DTG/3TC were included. Baseline characteristics, DTG/3TC maintenance rates, effectiveness, and metabolic parameters changes over 36 months were investigated. Results From July 2020 to April 2024, 305 people with HIV started DTG/3TC. Among them, 134 people with HIV followed for more than 36 months were included (16 treatment-naïve and 118 switching). Most were male (N=126, 94%), and the median age was 45.5 years. There were no cases of switching from DTG/3TC to other ARTs during the 36-month follow-up after starting DTG/3TC. All of the treatment-naïve group maintained HIV RNA < 50 copies/mL from 6 to 36 months after starting DTG/3TC. The rate of HIV RNA < 50 copies/mL at the 36 months in the switching group was 99.2% (117/118). In the treatment-naïve group, CD4 cell count increased from a median of 494 cells/uL at baseline to 795 cells/uL at 36 months (p=0.005). During the 36-month follow-up, there were no significant changes in lipid profile and body weight in both treatment-naïve and switching groups except for an increase in HDL cholesterol in the switching group (from median 45 mg/dL at baseline to median 49 mg/dL at 36-month, p=0.001). Effectiveness of Dolutegravir/Lamivudine for the treatments-naive and switching groups Conclusion In our long-term follow-up study conducted in South Korea, DTG/3TC worked effectively in viral suppression and CD4 count maintenance, and no significant adverse effects were observed on lipid profiles and body weight gain in both treatment-naïve and switching groups. Tolerability of Dolutegravir/Lamivudine for the treatments-naive and switching groups Disclosures All Authors: No reported disclosures

P-519. Long-acting Injectable PrEP Uptake and Persistence in a Sexual Health Clinic

Abstract Background HIV pre-exposure prophylaxis (PrEP), a powerful tool for HIV prevention, has traditionally been taken as a daily oral medication. Long-acting injectable (LAI) cabotegravir is superior to daily oral PrEP for HIV prevention and was approved for use as LAI-PrEP in 2021. We aimed to evaluate the uptake of LAI-PrEP and six-month LAI-PrEP persistence in a sexual health clinic. Participant characteristics (N=36) LAI: Long acting injectable PrEP: Pre-exposure prophylaxis Methods In February 2023, an LAI-PrEP pilot was implemented in a county sexual health clinic serving a diverse patient population in a designated ending the HIV epidemic in the South. Through state funding, patients at risk of HIV through sexual transmission were eligible to receive initial doses of LAI-PrEP at no cost and same-day initiation was encouraged. We evaluated the first 12 months of implementation. The primary outcome was LAI-PrEP persistence at 6 months. Statistical analyses were performed (SPSS version 29) using chi-square test for categorical variables with a significance level of 0.05. LAI-PrEP – long-acting injectable pre-exposure prophylaxis Results During the 12-month period, 55 people initiated LAI-PrEP, with 36 eligible for the six-month PrEP persistence evaluation. This population was 83% men, 31% Black, 58% Hispanic/Latino, and the median age was 32 (range 20-58) years. 75% received oral PrEP previously. LAI-PrEP six-month persistence rate was 72% (26 of 36). Among the 10 people with LAI-PrEP discontinuation, 1 transitioned to oral PrEP, 2 no longer had an indication for PrEP (change in serodifferent relationship status), and 7 were lost to follow-up. LAI-PrEP persistence differed by race (46% Black vs 88% white, p=0.007) and sexual orientation (37% heterosexual, 89% gay, 67% bisexual, p=0.019). LAI-PrEP – long-acting injectable pre-exposure prophylaxis Conclusion In the first year of LAI-PrEP implementation, LAI-PrEP uptake was favorable in our clinic, especially among priority populations for HIV prevention. Loss to follow-up was the most common reason for discontinuation, but change in PrEP method or loss of PrEP indication accounted for 30% of discontinuations. Nevertheless, the differences in persistence rates suggest a need for targeted interventions to improve long-term adherence in minority and heterosexual groups. Addressing PrEP persistence in these populations is crucial for optimizing the impact of LAI-PrEP in communities with a high burden of new HIV infections. Disclosures All Authors: No reported disclosures

P-792. Evaluation of the efficacy and safety of a short-course, daily, 4-month regimen including isoniazid, pyrazinamide, rifapentine and moxifloxacin (2HZPM/2HPM) for the treatment of drug-susceptible pulmonary tuberculosis in Taiwan (ESCAPE-TB): A multicenter study

Abstract Background The world is not on track to end the TB epidemic by 2030. Efficacious, safe, and shorter treatment regimens may significantly improve treatment success rates, and reduce TB incidence and mortality. The aim of this study is to evaluate the efficacy and safety of a short-course, 4-month regimen (2HZPM/2HPM) in the Asian population. Methods A prospective, 3-year, interventional study (Jan 2021-Dec 2023) enrolled adults with pulmonary TB, compared to historical controls (1:2 ratio) matched by age and sex, receiving standard 6-months treatment. The primary outcome was TB disease-free survival at 12 months after treatment assignment and proportion of grade 3 or 4 adverse events. A short-course regimen included a 2-months daily isoniazid(H), pyrazinamide(Z), rifapentine(P), and moxifloxacin(M), and 2 months of HPM. Sputum cultures were collected to assess early bactericidal effect at 2 months and to detect relapse at 12 months post-treatment.Fig 2.Treatment Duration of short-course, 4-months vs standard 6 months anti-tuberculous treatment: intent-to-treat analysis Results 109 subjects received short-course therapy, (80 males), with a mean age of 63.4 +/- 15.9 years; and 218 controls. Rates of adverse events were higher in the treatment group but were mostly Grade 1 (54.3% vs 28.7%, p < 0.001), and not significant for Grade 2 (p=0.28), Grade 3 (p=0.59) or Grade 4 (p=0.39). A higher discontinuation rate was found in the treatment group (65.7% vs 35.7%, p < 0.001). Reasons for discontinuation included: hyperbilirubinemia, GI upset, dizziness and others. Currently, 74.1% of the treatment group has completed treatment, 14.8% are under treatment, and 3.7% died, not related to TB. 2-months sputum culture conversion was 86.5 vs 93.4% (p=0.15), in the treatment versus control group, respectively. Survival at 12 months post-treatment was not significantly different between the treatment versus control group (91.7% vs 90.6%, p=0.17). Significant risk factor for treatment discontinuation included age >=55 years (adjusted HR 3.23, 95% CI: 1.27-8.19, p=0.01). Conclusion A short-course, 4 months regimen containing HPZM may be as efficacious as current standard, 6-month, anti-TB treatment regimens in Asian patients. Our study demonstrated a high rate of treatment discontinuation in Asian patients. This may be due to the older age of subjects with lower tolerability to adverse events. Disclosures All Authors: No reported disclosures

P-560. Evaluating the Use of Long-Acting Lenacapravir among Treatment-Experienced Adults with HIV in a Large Community-Based Clinic Network

Abstract Background Lenacapravir (LEN) is the first-in-class long-acting capsid inhibitor approved by the FDA in December 2022 for the treatment of multi-drug resistant HIV in adults. It is administered by subcutaneous injection every six months in combination with other antiretrovirals (ARV). It is indicated for heavily treatment-experienced people with HIV (PWH). We assessed the use of long-acting LEN within the CAN Community Health Network. Methods A retrospective analysis of electronic medical records within the CAN Community Health Network of 23 clinics located throughout six US states. People with HIV who received one or more injections of LEN for treatment between December 2022 and April 2024 were included. Demographic characteristics, HIV viral load, CD4 count and composition of pre-LEN ARV regimens were studied. Results Twenty-four PWH were identified as receiving one or more injections of LEN between December 2022 and April 2024. The median age was 58 years; 79% were male, 67% White and 71% Non-Hispanic (Table 1). Mean number of injections received was 2. Pre-LEN HIV VL was >50 copies/mL in 8 PWH (33%) and pre-LEN HIV VL was < 50 copies/mL in 16 PWH (67%). Five PWH (21%) had a pre-LEN CD4 count < 200 and 19 PWH (79%) had a pre-LEN CD4 count >200. Post-LEN HIV VL decreased in all eight patients with HIV VL >50 copies/mL (Table 2). Pre-LEN ARV regimens included a median of 4 active agents with 92% of them containing integrase inhibitors (INSTIs), 71% NRTIs and 58% protease inhibitors (PIs) (Table 3). Reasons for switching to a LEN-combination regimen in those with HIV VL < 50 included: simplification, side effects or intolerance to oral ARVs and non-adherence. Three (13%) patients stopped LEN due to injection site reactions (ISRs), 1 patient (4%) stopped due to side effects, 2 patients (8%) were lost to care and 1 patient (4%) was switched to an oral alternative due to travel. Conclusion The majority of PWH who were switched to LEN-combination regimens were older males with HIV VL < 50 copies/mL. Reasons for switching included simplification, side effects to other ARVs and non-adherence. Of those with HIV VL > 50 copies/mL prior to switching to a LEN-combination regimen, all had a decrease in their HIV VL. The most common reason for discontinuation was ISRs. Sample size was small and a longer duration of follow-up is needed. Disclosures Jessica A. Altamirano, MD, FIDSA, Gilead Sciences: Speaker's Bureau

Efficacy and safety of first-line targeted synthetic DMARDs in rheumatoid arthritis patients with chronic kidney disease.

To evaluate the efficacy and safety of first-line targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). This retrospective cohort study included 216 patients with RA prescribed their first tsDMARDs at two hospitals between 2013 and 2022. Dose reduction and contraindication guidelines for tsDMARDs according to kidney function were followed. The patients were categorised by kidney function and tsDMARD modality. The primary outcome was the 24-month drug retention rate, and the secondary outcomes were changes in the Disease Activity Score 28-C-reactive protein (DAS28-CRP) level, prednisolone dosage, and reasons for discontinuation. The 24-month drug retention rates according to the estimated glomerular filtration rate (eGFR) (≥60, 30-60, or < 30 mL/min/1.73 m2) were as follows: all tsDMARDs (46.0, 44.1, 47.1%), tofacitinib (55.9, 53.3, 66.7%), baricitinib (64.2, 42.0%), and peficitinib (36.4, 44.1, 40.0%). Even in groups with lower kidney function, the drug retention rate was maintained (adjusted hazard ratio was 1.14 (95% confidence interval, 0.81-1.62), p= 0.45). Patients had a decreased DAS28-CRP (p< 0.01) and a reduced prednisolone dosage (p< 0.01) over the six-month period following tsDMARD initiation. The incidence of herpes zoster and deep vein thrombosis (DVT) was higher in the group with an eGFR <30 mL/min/1.73 m2, but not statistically significant. tsDMARDs have demonstrated efficacy and safety in patients with RA and CKD; however, clinicians should consider the potential for herpes zoster and DVT in patients with eGFR <30 mL/min/1.73 m2.

P0658 Comparison of the Efficacy and Safety of Immunomodulator Use in Geriatric and Non-Geriatric Patients with Inflammatory Bowel Disease

Abstract Background The patterns of medication use among elderly inflammatory bowel disease patients vary due to several factors. This study aims to present the outcomes of immunomodulator therapy in both geriatric and non-geriatric patient groups, highlighting differences in treatment effectiveness, reasons for discontinuation, and the incidence of side effects between the two groups. Methods A retrospective database was established by reviewing the records of inflammatory bowel disease patients aged 18 and older who received immunomodulator therapy at our clinic over a seven-year period. Patients aged 65 years and above were designated as the geriatric cohort. In addition to demographic and clinical variables, disease activity in ulcerative colitis patients was assessed using the Mayo Disease Activity Index and the Rachmilewitz Endoscopic Activity Index, while the Harvey-Bradshaw Index was employed for Crohn’s disease patients. Results The study included 102 patients, comprising 44 with ulcerative colitis and 58 with Crohn’s disease. The median age was 66.5 years (range: 23–87), with 54 patients (52.94%) classified as geriatric (≥65 years). Immunomodulator therapy was discontinued due to side effects in 31 patients (30.39%) and due to remission in 11 patients (10.78%). Additionally, 23 patients (24.21%) showed no response to the treatment. No significant differences were observed between the geriatric and non-geriatric groups regarding the type of inflammatory bowel disease, duration of therapy, concomitant treatments, reasons for discontinuation, side effects, malignancy occurrence, malignancy type, or mortality. Conclusion With careful patient selection and close monitoring, immunomodulator therapy in elderly inflammatory bowel diseasepatients can achieve similar effectiveness and risk of side effects as observed in younger patient groups.

P0953 Real world effectiveness and safety of filgotinib in Ulcerative Colitis: 1 year follow-up results of the ICC registry

Abstract Background Filgotinib is a preferential JAK1-inhibitor approved for the treatment of ulcerative colitis (UC). The ICC registry was developed to evaluate the effectiveness and safety of advanced therapies in inflammatory bowel disease (IBD). Here, we report the one-year follow-up results of filgotinib in patients with UC. Methods Fourteen hospitals prospectively enrolled UC patients initiating filgotinib in the Dutch ICC registry. Treatment persistence was assessed by Kaplan-Meier survival analysis. Clinical remission (i.e. Simple Clinical Colitis Activity Index [SCCAI] ≤ 2) and corticosteroid-free clinical remission rates were assessed at 12, 24 and 52 weeks for all patients who were not in remission at baseline, based on SCCAI score, faecal calprotectin and/or endoscopy. Patients lost to follow up were considered as treatment failure. Reasons for treatment discontinuation and adverse events were recorded. Results Eighty-three UC patients (47% females) were enrolled between January 2022 and October 2023. Mean age and disease duration at baseline were 41 [sd ± 16] and 12 years [sd ± 9], respectively. A total of 49 (59%) patients had used up to two advanced therapies and 34 (41%) patients had used three or more. At baseline, 75 patients (90%) had active disease of whom 24 (32%) used oral corticosteroids. After one year of follow-up, 58.8% of patients still used filgotinib (Figure 1). At week 12, 24 and 52, corticosteroid-free clinical remission rates were 57.1%, 32.7% and 34.6% respectively (Figure 2). Reasons for treatment discontinuation were primary non-response (n=17), secondary loss of response (n=13), side effects (n=3) or other reasons (n=4). Fifty-seven adverse events were recorded (19 infections). Ten infections required treatment with antibiotics or antiviral therapy, none of them led to hospitalization or therapy discontinuation. No thromboembolic events were reported. Conclusion The results of this real world study show that, even in a therapy-refractory UC population with an average disease duration of 12 years, more than half of the patients still used filgotinib and one third of patients was in corticosteroid-free clinical remission after one year of follow-up. No new safety signals were found.

P1031 Effectiveness and safety of oral vancomycin in the treatment of non-primary sclerosing cholangitis paediatric Inflammatory Bowel Disease (non-PSC PIBD) patients: a real-world single-center cohort study

Abstract Background Oral vancomycin has had limited use in paediatric Inflammatory Bowel Disease (PIBD), with reported efficacy in primary sclerosing cholangitis (PSC-PIBD)1, acute severe colitis as part of a quadruple antibiotic regimen2, and very early onset IBD3. This study evaluates its effectiveness and safety as single-agent therapy in non-PSC PIBD patients. Methods This single-centre retrospective cohort study included PIBD patients started on oral vancomycin for active IBD or steroid/topical therapy dependency from 01/2017 to 08/2024. Exclusion criteria were PSC diagnosis, positive/equivocal stool test for C. difficile, another induction treatment started within 3 weeks prior and vancomycin use solely in a quadruple regimen2. Disease activity was assessed using PUCAI/wPCDAI, faecal calprotectin (FC), blood parameters at baseline, 1, 3, 6 and 12 months. Treatment regimen, duration, reasons for discontinuation and adverse events (AEs) were recorded. Vancomycin was started at 250mg in patients ≥30kg or 125mg in those &amp;lt;30kg TDS/QDS and tapered in responders after ≥1 month. Results Of 72 patients identified, 31 were included (16 males): 23 (74%) had Ulcerative Colitis (UC), 4 (13%) IBD unclassified (IBDU), 4 (13%) Crohn’s Disease (CD). At baseline, 5/31 were in clinical remission, with 2 also in biochemical remission but drug dependent. Initial vancomycin dosage was 17.5mg/kg/day (IQR 15.3-21.6), with a median duration of 4 (IQR 1-9) months. Concomitant medications are shown in Table 1: 10/31 (32%) were on biologics, with 4 able to discontinue and 2 to reduce biologic doses later. Overall, 17/31 (55%) patients (13 UC, 3 IBDU, 1 CD) achieved/maintained clinical and biochemical remission (Group 1), with 15 reducing/stopping other treatments. Conversely, 14/31 (45%) discontinued vancomycin due to non-response (11) or intolerance (3) (Group 2), with 11 stopping within 1 month. At baseline, Group 1 had lower disease activity score and platelet count than Group 2 (Table 1). A striking difference in response was noticed at 1 month (Figure 1), with FC in Group 1 dropping from 686μg/g (IQR 376-1143) at baseline to 60μg/g (IQR 25-160) at 1 month (p=0.001), while remaining high in Group 2 (p=0.52). In Group 1, 5/17 (29%) stopped vancomycin while in stable remission after 4 (IQR 2-9) months, with 3 restarted due to relapse, recapturing remission in 2/3. No severe AEs were reported. Conclusion Oral vancomycin was rapidly effective and safe, with 55% of non-PSC PIBD patients achieving/maintaining remission and 48% able to reduce/stop concomitant treatments. It was most effective in mildly active disease, especially UC/IBDU, and may offer a medium to long-term treatment option, with promising results in biologic-resistant but antibiotic-responsive PIBD patients.

OP31 Phase 1b study of SOR102, a novel, orally delivered bispecific anti-TNF/anti-IL-23 domain antibody in patients with mild to severe ulcerative colitis

Abstract Background SOR102 is a novel, orally delivered, bispecific antibody construct containing two humanized single domain antibodies (SDA) targeting TNFα and IL-23p19 connected by a trypsin-labile linker, enabling monomer separation within the small intestine and inhibition of TNFα and IL-23 activity within GI tissue. SOR102 SDAs were engineered for stability to intestinal and inflammatory proteases. The Phase 1, first-in-human study (SOR102-101; NCT06080048) had 3 parts. Parts 1 and 2 enrolled healthy subjects. Here, we present results for Part 3, a Phase 1b randomized, double-blind, placebo-controlled study in patients (pts) with mild to severe UC. Methods Pts with Mayo endoscopy score (ES) ≥2, rectal bleeding score (RBS) ≥1 and stool frequency score (SFS) ≥1 were randomized 1:1:1 to receive SOR102 810mg BID, SOR102 810mg QD, or placebo for 6 weeks. The primary objective was safety and tolerability of SOR102. Secondary objectives were the concentration of SOR102 and monomers in serum, urine and feces, and antidrug antibodies. Exploratory efficacy endpoints were Mayo Score (MS) and modified MS (mMS) clinical response, symptomatic remission (SR), and mean change from baseline in MS, mMS, UC-100 score, SFS, RBS, fecal calprotectin (FC), C-reactive protein (CRP), and Robarts Histopathology Index (RHI). Safety and efficacy were evaluated in pts who received ≥1 dose of SOR102 or placebo. Efficacy was also evaluated in pts who completed the study. Results Twenty-two pts were randomized (SOR102 810mg BID=9; SOR102 810mg QD=7; placebo=6); 17 pts completed the study. Reasons for discontinuation were worsening of UC (N=2), study schedule non-compliance (N=2) and consent withdrawal (N=1). Mean age was 50 yrs; 45% were male; median MS was 8 (range 6-11). Most pts were advanced therapy-naïve. TEAEs were reported in 57%, 29%, and 50% of pts receiving SOR102 810mg BID, SOR102 810mg QD, or placebo, respectively (Table 1); most were mild-to-moderate in severity. One AE (SOR102 810mg BID arm) was considered possibly related to SOR102 (abdominal pain of mild severity). One serious AE of worsening of UC that led to hospitalization occurred in the SOR102 810mg BID arm. Figure 1 shows exploratory efficacy results. Higher rates of MS and mMS clinical response and SR, and greater decreases from baseline in MS, mMS, UC-100, combined SFS+RBS, and RHI were observed in the SOR102 BID arm compared with QD and placebo. There were no significant differences in FC and CRP between the treatment groups. Conclusion SOR102 was safe and well tolerated. Efficacy across multiple endpoints was observed in the SOR102 BID arm compared to QD and placebo, despite the short treatment duration. Further clinical development of SOR102 is warranted.