Common Reason For Discontinuation Research Articles

Long-term efficacy and safety of adjunctive perampanel in pediatric patients aged 4–19 years with epilepsy: a real-world study

This study determined the 24-month outcomes of perampanel treatment in children and adolescents with epilepsy. The percentage of ≥ 50% responders was 47.3% (139/294) at 12 months and 49.0% (144/294) at 24 months. A 100% reduction in seizures for more than 12 months was observed in 12.2% (36/294). Discontinuation occurred in 39.8% (117/294). The most common reason for discontinuation was adverse events (29.1%, 34/117). Baseline seizure frequency was higher in children aged < 12 years than in patients aged ≥ 12 years; however, the percentage of seizure reduction and ≥ 50% responders did not significantly differ between the two groups. The rate of early discontinuation was higher (p < 0.001) and the duration of perampanel treatment was shorter in children aged < 12 years (p = 0.001). Most children aged < 12 years discontinued PER due to inadequate effectiveness, while adverse event was the most common reason in patients aged ≥ 12 years (p = 0.045). Only slow titration was significantly associated with ≥ 50% of responders. In conclusion, this study showed that perampanel can be utilized effectively and safely for a prolonged period in pediatric patients aged 4 to < 12 years, as well as in patients aged 12 years and older.

Real-world retention rates and effectiveness of secukinumab in psoriasis: Results from a multicenter cohort study (RAILWAY).

Psoriasis is a chronic, immune-mediated inflammatory skin disease with a high negative impact on patient's quality of life. Secukinumab, the first interleukin 17A inhibitor, has been used for the systemic treatment of psoriasis, but its long-term, real-world retention rates in Japan have not been fully investigated. In this multicenter, noninterventional, retrospective chart review study, the retention rate of secukinumab and its effectiveness among patients with psoriasis in Japan was evaluated up to 5 years. Data of patients who received secukinumab after December 26, 2014, were collected from medical charts obtained from seven sites, all certified for biologics use by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors affecting secukinumab retention, reason for drug discontinuation, and effectiveness data were collected. The primary end point was secukinumab retention rate at week 52. A total of 123 patients were included in the analysis. Of these, 27 patients discontinued secukinumab by week 52, yielding a 78.0% (95% confidence interval, 69.6-84.4) retention rate at week 52. For patients whose Psoriasis Area and Severity Index (PASI) score was available, mean ± standard deviation PASI at baseline and at week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively. During the entire study period, "insufficient response" was the most common reason for discontinuation, and "history of biologics use" was a factor significantly associated with secukinumab discontinuation (hazard ratio, 1.72; p = 0.018). This study demonstrates the real-world retention rate and effectiveness of secukinumab in patients with psoriasis in Japan for up to 5 years and provides clinical insights into psoriasis treatment strategies.

Short-term outcomes after sodium-glucose cotransporter-2 inhibitor initiation in a cohort of heart failure patients.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients. We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n=6), hypotension (n=5), and AKI (n=4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC)=75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC=72.0, ECI 65.7-78.7); LVEF (AUC=67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC=66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC=81.1, ECI 74.8-87.2); baseline SCr (AUC=67.4, ECI 58.7-75.5); LVEF (AUC=68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC=67.2, ECI 58.2-76.0). A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.

Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy

BackgroundProfessional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.MethodsThis was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan–Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.ResultsHere we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994–4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.ConclusionsDOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.

Medication changes implemented during medication reviews and factors related to deprescribing: Posthoc analyses of a randomized clinical trial in geriatric outpatients with polypharmacy.

To provide posthoc analyses of a clinical trial that reported beneficial effects of medication reviews on health-related quality of life. Specifically, to describe the medication changes with a focus on deprescribing and to explore patient- and medication-related factors that may identify patients most likely to benefit from medication reviews. Posthoc analyses of data from a pragmatic, nonblinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients treated with ≥9 medicines. In the medication review group (n = 196), 26% of the medicines prescribed at baseline were discontinued with 82% still being discontinued after 13 months. The most common reason for discontinuation was lack of indication (72% of discontinuations). The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/15 = 73% discontinued vs. 1/12 = 8% in usual care), acetylsalicylic acid (20/48 = 42% vs. 2/47 = 4%), simvastatin (18/48 = 38% vs. 2/58 = 3%), zopiclone (23/59 = 39% vs. 4/54 = 7%), quinine (9/14 = 64% vs. 6/16 = 38%), citalopram (4/18 = 22% vs. 0/20 = 0%) and tramadol (18/37 = 49% vs. 8/30 = 27%). Factors associated with number of deprescribed medicines included: number of prescribed medicines, Drug Burden Index, patient motivation for medicine changes, and prescriptions of metoclopramide, iron preparations, antidepressants other than selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or drugs for urinary incontinence. Physician-led medication reviews resulted in persistent deprescribing of medicines in older polypharmacy patients treated with ≥9 medicines. Motivation for having their medicine changed, treatment with more medicines, and a higher burden of sedative and anticholinergic medicines characterized the patients most likely to benefit from physician-led medication reviews.

Prosthesis nonuse and discontinuation in United States veterans with major limb amputation: Results of a national survey.

Prosthesis use in persons with amputation can improve mobility and functional independence. Better understanding of the reasons for and outcomes associated with prosthesis nonuse is important to optimize function and long-term health in persons with amputation. Study objectives were to describe the rate, reasons for, and factors associated with never using or discontinuing prosthesis use in United States (US) veterans with amputation. Cross-sectional study design. The study used an online survey to assess prosthesis use and satisfaction in veterans with upper-limb and lower-limb amputation. Survey participation invitations were distributed by email, text message, and mail to 46,613 potential participants. The survey response rate was 11.4%. After exclusions, an analytic sample of 3,959 respondents with a major limb amputation was identified. The sample was 96.4% male; 78.3% White, with mean age of 66.9; and mean of 18.2 years since amputation. The rate of never using a prosthesis was 8.2%, and the rate of prosthesis discontinuation was 10.5%. Functionality (62.0%), undesirable prosthesis characteristics (56.9%), and comfort (53.4%) were the most common reasons for discontinuation. After controlling for the amputation subgroup, the odds of prosthesis discontinuation were higher for those with unilateral upper-limb amputation, female gender, White race (compared with Black race), diabetes, above-knee amputation, and lower prosthesis satisfaction. Prosthesis satisfaction and quality of life were highest for current prosthesis users. This study adds new understanding regarding the rate and reasons for prosthesis nonuse in veterans and highlights the important relationship between prosthesis discontinuation and prosthesis satisfaction, quality of life, and satisfaction with life.

Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (aged 4 to

PurposeTo evaluate the safety and tolerability of adjunctive perampanel in a Japanese subpopulation of Study 311 (NCT02849626), which was a global, multicenter, open-label, single-arm study of children (aged 4 to <12 years) with inadequately controlled focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS). MethodsStudy 311 comprised a Core Study, Extension A, and Extension B; this report focuses on the Japanese patient subgroup in the Core Study only. In the Core Study, Japanese patients (FOS only) received adjunctive perampanel ≤12 mg/day in a 23-week Treatment Phase. Endpoints included safety/tolerability (primary) and median percent change in seizure frequency per 28 days from baseline. Patients were stratified by age and concomitant enzyme-inducing anti-seizure medication (EIASM) use. ResultsOf 65 enrolled Japanese patients, 56 completed the Core Study and nine withdrew. The most common reason for discontinuation was adverse events (AEs) (n = 4 [6.2%]). The mean (standard deviation) daily dose of perampanel in Japanese FOS patients was 5.8 (2.2) mg/day. During the Core Study, treatment-emergent AEs (TEAEs) were reported by 89% of Japanese patients, most commonly nasopharyngitis (28%) and somnolence (28%). The median percent reduction in seizure frequency per 28 days from baseline was 37% and the lower limit of the 95% CI was greater than 10.5%, satisfying the pre-defined efficacy criteria. Perampanel was effective regardless of age or concomitant EIASM use. ConclusionPerampanel as adjunctive therapy is generally safe, well-tolerated, and efficacious in Japanese children aged 4 to <12 years with FOS (with/without FBTCS).

Efficacy and safety of elranatamab by age and frailty in patients (pts) with relapsed/refractory multiple (RRMM): A subgroup analysis from MagnetisMM-3.

8040 Background: Multiple myeloma is predominantly a disease of elderly and frail pts, who are often ineligible for intensive therapies. Data from the ongoing Phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in pts with RRMM and no prior BCMA-directed therapy (Cohort A). Here we report results for subgroups of pts by age and frailty. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups of pts within Cohort A (n = 123) were analyzed by age: &lt; 65 (n = 43) vs ≥65 years n = 80), and frailty: non-frail (n = 84) vs frail (n = 39). A simplified frailty scale was used (Facon et al, Leukemia 2020). Results include data up through ~12 months after last pt initial dose. Results: The median treatment duration was 8.2 vs 5.5 mo in the &lt; 65 vs ≥65 years, and 6.4 vs 5.6 mo in the non-frail and frail subgroups, respectively. Discontinuation occurred in 62.8% vs 67.5% of pts aged &lt; 65 vs ≥65 years and in 63.1% vs 71.8% of the non-frail vs frail groups, respectively. The most common reason for discontinuation in all subgroups was progressive disease, 51.2%, 32.5%, 42.9%, and 30.8% of &lt; 65, ≥65 years, non-frail, and frail subgroups, respectively. The objective response rate (ORR) (95% CI) was 58.1% (42.1%, 73.0%) vs 62.5% (51.0%, 73.1%) for pts aged &lt; 65 vs ≥65 years. Median duration of response was not reached in either age subgroup. The probability of maintaining response (95% CI) at 12 mo was 74.1% (51.0%, 87.5%) vs 73.8% (55.7%, 85.4%) for pts aged &lt; 65 vs ≥65 years. The ORR (95% CI) for non-frail pts was 63.1% (51.9%, 73.4%) vs 56.4% (39.6%, 72.2%) for frail pts. Median duration of response was not reached in either frailty subgroup. The probability of maintaining response at 12 mo (95% CI) was 76.0% (60.2%, 86.2%) vs 70.5% (41.9%, 86.9%) for non-frail vs frail pts. Any Grade treatment-emergent adverse events (TEAEs) were reported in 100% of pts in the study. Grade 3/4 TEAEs were reported in 74.4%, 68.8%, 73.8% and 64.1% of pts in &lt; 65, ≥65, non-frail and frail subgroups, respectively. Infections (Any Grade; Grade 3/4; Grade 5) were reported in 72.1%, 32.6% and 4.7% vs 68.8%, 40.0% and 6.3% in &lt; 65 and ≥65 pts, respectively, and in 70.2%, 38.1% and 4.8% vs 69.2%, 35.9% and 7.7% in non-frail and frail pts, respectively. The rate of cytokine release syndrome was similar in patients with respect to age ( &lt; 65, 58.1%; ≥65 years, 57.5%) and frailty groups (non-frail, 57.1%; frail, 59.0%). Immune effector cell-associated neurotoxicity syndrome was reported in 2.3%, 6.3%, 6.0% and 2.6% of pts in &lt; 65, ≥65, non-frail and frail subgroups, respectively. Conclusions: Elranatamab is efficacious and has a manageable safety profile in elderly or frail pts with RRMM and may be a treatment option for those ineligible for more intensive myeloma therapies. Clinical trial information: NCT04649359 .

Phase I trial of enzalutamide (Enz) plus the glucocorticoid receptor antagonist relacorilant (Rela) for patients with metastatic castration resistant prostate cancer.

5062 Background: Resistance to androgen receptor (AR) targeted therapies is common in mCRPC. Glucocorticoid receptor (GR) expression increases with AR inhibition in patients (pts) and blockade of GR signaling inhibits CRPC growth in preclinical models when combined with AR blockade. We thus conducted a phase I study of the combination of rela and enz in patients with mCRPC. Methods: The study used a 6+3 design to assess safety and pharmacokinetics (PK) of the 2-drug combination. The starting dose of rela 100mg/day was chosen based on current clinical studies indicating this dose was both safe for daily dosing and pharmacologically active and the starting dose for Enz was 120mg based on anticipated drug-drug interactions. Escalating doses of rela were combined with Enz 120 using pre-specified dose escalation rules. An additional 12 patients were to be assessed at the MTD to refine safety and PK profiles. Primary endpoint was safety of the combination and to establish safe and pharmacologically active doses of both agents. Key secondary endpoints were tumor response per RECIST 1.1 criteria and progression-free survival (PFS; defined as either PSA progression, radiographic progression or death). PSA was measured after 12 weeks or at the last time at which PSA data was available, including times &lt;12 weeks. Results: 35 pts were enrolled. Pts had a median age of 74 (range 62-85) and baseline PSA of 89.5 (range 7.3-2391). 100% had prior potent AR signaling inhibitor (abi or enz) with 89% receiving prior enz, 94% prior abi, 83% prior both. 69% of pts received prior docetaxel. Median PSA change was 0.1%. Enz 120mg + Rela 100mg and Enz 120+Rela 150 were found to be safe and tolerable and achieved desirable Enz PK. DLTs were noted in 3 pts at the 200mg Rela dose, which was deemed to have exceeded the MTD, which was thus defined as 150mg Rela+120mg Enz. Most common ≥ grade 3 treatment related adverse events (TRAEs) were fatigue (11% of pts), anemia (9%), abdominal pain (6%) and pericardial effusion (6%). Median PFS was 2.5 months for 21 of 35 evaluable pts. Best response per RECIST 1.1 were Not Evaluable (40%), SD (34%) &amp; PD (26%). No CR or PR were noted. Most common reasons for discontinuation from trial included progressive disease/hospice (82%), AEs (12%), physician discretion (3%) &amp; death (3%). 2 pts remain on trial as of data cutoff (12/31/22). Conclusions: The combination of enzalutamide and relacorilant was safe &amp; largely well tolerated. The majority of pts were discontinued from trial due to progressive disease or hospice. Further analyses of secondary &amp; correlative endpoints such as translational/endocrine biomarkers, GR target gene expression and circulating tumor cells are ongoing. Clinical trial information: NCT03674814 .

Pevonedistat plus belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome: A phase I multicenter study.

e19015 Background: Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy, with particularly dismal prognosis in the relapsed or refractory (R/R) setting, with a median overall survival of approximately 6 months. There has been increasing interest in novel therapeutic approaches to intelligently harness cellular pathways to improve outcomes in this difficult to treat population. Pevonedistat, a first-in-class NEDD8 inhibitor, and Belinostat a HDAC inhibitor work synergistically in AML cells and human xenograft AML models supporting the clinical rationale for this Phase I study. Methods: A Phase I dose-escalation study with a 3+3 design was performed to assess safety and tolerability of pevonedistat plus belinostat. Beliniostat (D1-5) and Pevonedistat(D1,3,5) were administered in a 21 day cycle until disease progression or unacceptable toxicity. Primary endpoint was identification of MTD/RP2D, secondary endpoints included toxicity, efficacy, pharmacokinetic interactions, and pharmacodynamic studies. Results: 18 patients (67% female; median age 67.5 (41-74)), 16 of whom had AML, were treated at 5 dose levels (belinostat 800-1000mg/m2, pevonedistat 20-50mg/m2), no dose limiting toxicities were noted. Average number of prior lines of therapy was 3. Most Grade 3 or 4 toxicities were hematologic (Table). Maximum number of cycles reached was 8. Best response was stable disease in four patients, and CR in one patient. The remainder had progressive disease or were not evaluable. Most common reason for discontinuation was disease progression (67%), 11% treatment ended per protocol criteria, 6% pursued alternative therapy, 6% due to side effects. The patient achieving CR was a 54 year old female with BRAF and TET2 mutation, primarily refractory to 7+3 and also unresponsive to second line azacitidine and venetoclax. After CR, she received an allogeneic stem cell transplant and remains in remission with 2 years of follow up. Conclusions: The combination of pevonedistat plus belinostat is safe in adult R/R AML with a manageable, primarily hematologic profile, and modest but notable activity in this heavily treated population. This regimen may be effective as a bridge to transplant in some patients. MTD was not reached in this study. Clinical trial information: NCT03772925 . [Table: see text]

Longitudinal, prospective cardiovascular and metabolic risk in treatment-naive patients with chronic myeloid leukemia in chronic phase (CML-CP) starting tyrosine kinase inhibitor (TKI) therapy in a real-world setting.

7053 Background: Multiple TKIs used in the treatment (tx) of CML have been associated with the development of cardiovascular/metabolic (CV/Met) comorbidities, yet no study to date has prospectively and systematically assessed CV/Met parameters after TKI initiation. CA180-653 (NCT03045120) is a non-interventional, prospective, real-world study characterizing the effects of TKIs (dasatinib [DAS], imatinib [IM], nilotinib [NIL], and bosutinib [BOS]) on CV/Met risk factors in patients (pts) with CML-CP in routine care. Baseline CV/Met risks were previously reported (Mauro, GCOS 2019). Here, we report data from the final 2-year follow-up. Methods: Adult pts with newly diagnosed CML-CP due to start tx with DAS, IM, NIL, or BOS were enrolled; the BOS cohort was not analyzed independently due to small sample size. Pts were followed for 24 mo. Blood/urine samples, CV/Met assessments, coronary calcium scoring, echocardiography, and cytogenetic/molecular response assessments were collected at routine office visits at predetermined timepoints. The primary endpoint was change in CV/Met risk from baseline. Results: At the end of follow-up, 118 pts were enrolled; 49 received DAS, 47 IM, 16 NIL, and 6 BOS. Of these, 83 (70.3%) pts completed the study and 35 (29.7%) discontinued; the most common reason for discontinuation was withdrawal of consent (n = 19). No pts died from CML. At baseline, median age was 57 (range, 20–97) y; 59.3% of pts were male and 83.9% were White. Sixty-two (52.5%) pts had CV/Met risk factors at baseline, including hypertension (n = 45/62; 72.6%), hyperlipidemia (n = 33/62; 53.2%), diabetes (n = 19/62; 30.6%), and arrhythmia (n = 10/62; 16.1%). Over the study period, 1 (3.4%) patient receiving DAS and 2 (6.9%) receiving IM developed coronary artery calcification; 2 (9.1%) pts receiving IM developed pericardial effusion. Median left ventricular ejection fraction on 2D echocardiogram was normal for all TKIs at baseline (65.4% [range, 27–81]) and end of study (65.4% [range, 40–80]). Systolic and diastolic blood pressure increased from baseline only in pts who received NIL. Blood glucose levels increased from baseline for DAS, IM, and NIL (median: 1.9, 4.9, and 5.8 mg/dL, respectively), and low-density lipoprotein levels decreased from baseline in all 3 cohorts (median: 72.7, 52.1, and 56.3 U/L, respectively); data from the NIL group were limited by the small sample size. There was 1 death from myocardial infarction related to NIL. Conclusions: These findings suggest more than half of pts with CML-CP have CV/Met risk factors at baseline. At end of study, there was indication of CV/Met effects based on TKI selection. This highlights the importance of appropriate TKI selection based on pt comorbidity characteristics, along with close monitoring and management of CV/Met risks throughout tx. Clinical trial information: NCT03045120 .

0584 Sodium Oxybate Treatment Patterns in Narcolepsy Patients: A Propensity Score–Matched Cohort Study Subanalysis

Abstract Introduction Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. Patients treated with available immediate-release oxybates are required to awaken for a second dose 2.5–4 hours after the bedtime dose to cover a full night of sleep. This study characterized SXB treatment patterns and discontinuation in narcolepsy patients. Methods Mayo Clinic patients from 1975–2020 were identified using an electronic health record–based search. Patients with ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (identified using a natural-language-processing [NLP] algorithm) were included. NLP was used to identify SXB non-use events with manual chart reviews performed to characterize reasons for discontinuation, switching, or missing the second dose and effects of missing the second dose. Results Of the patients with narcolepsy prescribed SXB (n=351; mean age at first diagnosis code observed at Mayo Clinic, 32 y [IQR: 23.2–46.1]; 65.5% female; 92.3% white), 113 (32.2%) had clinical notes indicating discontinuation of SXB, with 71 (20.2%) including reasons for discontinuation. The most common reasons for discontinuation (n≥5) included lack of efficacy (n=11), side effects (n=10), gastrointestinal side effects (n=10), neurological side effects (n=9), psychiatric side effects (n=8), lack of access (insurance/cost, n=10), and resolution/absence of cataplexy (n=5). Mentions of switching from SXB to other drugs (n=12 patients) included switching to stimulants (mixed amphetamine salts, n=3; dextroamphetamine, n=2; methylphenidate, n=1), sedative hypnotics (zolpidem, n=2), antidepressants (mirtazapine, n=1), and wake-promoting agents (solriamfetol, n=1). Of the 38 patients (10.8%) with mentions of missing the second nightly SXB dose, reasons were recorded for 24 (63.2%), including inability to wake up (n=14), forgetting the second dose (n=3), and having to wake up early the following day (n=3). Consequences of missing the second dose were recorded for a small subset (increased cataplexy, n=4; lower daytime alertness, n=3; awakens earlier, n=1; tiredness, n=1). Conclusion Limited data are available regarding real-world use of SXB. This novel study used a combination of NLP algorithm and manual chart review to identify difficulties patients have with the second, middle-of-the night immediate-release oxybate dose and patient-experienced consequences of not adhering to the prescribed dosing regimen. Support (if any) Avadel Pharmaceuticals

Libido-sexual disorders and abandonment of injectable contraceptives among users of the Ivorian Association for Family Well-Being in Korhogo, Côte d'Ivoire.

The recent introduction of modern contraceptive methods in resource-limited countries is confronted with the occurrence of undesirable effects that hinder their use in the long term. This study conducted among the users of the Ivorian Association for Family Well-Being in Korhogo describes the libido-sexual problems associated with the discontinuation of injectable contraceptives in former users. The objective of the study was to identify the factors that led to the abandonment of injectable contraceptives among female users of the Ivorian Association for Family Well-Being in Korhogo between 2018 and 2019. Qualitative data were collected from 15 former users (24-38 years old) of injectable contraceptives duration of 2-3 months. Additional data were collected from five health workers aged 35-60 years. In-depth interviews were conducted to explore the experience with injectable contraceptives and reasons for discontinuation. Following data collection, audio-recorded data were transcribed, translated, and coded using thematic analysis through an inductive approach. Side effects identified as associated with injectable contraceptives include libido-sexual disorders, unusual bleeding, and weight gain. The most common reason for discontinuation were libido-sexual disorders, which impacted the households' intimacy and provoked their abandonment or the change of contraceptive methods among injectable contraceptive users. Adverse events were dominated by libido-sexual disorders, unusual bleeding, and weight gain leading to the abandonment or change of the contraceptive. These results suggest points of intervention for increasing continuation among users. This intervention should include training of health workers to investigate and manage adverse events related to the use of injectable contraceptives and the improvement of communication between health workers and users on adverse events of injectable contraceptive use.

PO-03-133 BOTH OVERUSE AND UNDERUSE OF ORAL ANTICOAGULATION POST-ATRIAL FIBRILLATION ABLATION IN A LARGE HEALTHCARE SYSTEM

Guidelines recommend that decisions regarding oral anticoagulation (OAC) post ablation for atrial fibrillation (AF) should be based solely on the patient’s stroke risk profile, regardless of the outcomes of the procedure. The adherence to this recommendation in clinical practice has not been examined. To provide real-world data about adherence to anticoagulation guidelines after AF ablation. We included patients undergoing AF ablation in one of 8 hospitals of Northwell Health between 2014 and 2022. We excluded patients without continuous OAC for at least 2 months post-ablation and without a complete 3- and 12-month follow-up. Adherence to OAC guidelines was defined as continuing OAC for males with CHA2DS2-VASc≥2 and females with CHA2DS2-VASc≥3 and discontinuing OAC for the rest. A subgroup analysis of patients based on their CHA2DS2-VASc scores (0, 1, 2, and ≥3) was performed. Exploratory clinical endpoints included AF recurrence, stroke/transient ischemic attack, bleeding events, and all-cause mortality. Out of 900 patients, 69 (7.7%) and 187 (20.1%) discontinued OAC at 3- and 12-months post-ablation, respectively (Figure 1). Among patients who discontinued OAC at 12 months, 91 (48.6%) met indication for OAC. In contrast, among those without OAC indication, 36 (54.5%) patients remained on OAC at 12 months. Patients who discontinued OAC were younger with mostly paroxysmal AF and fewer comorbidities; lending to lower CHA2DS2-VASc scores (all p< 0.001). Specifically, 64.7%, 46.6%, 22.3% and 10.6% of patients with CHA2DS2-VASc of 0, 1, 2, and ≥3 respectively, discontinued OAC at 12 months (Table 1). Among those who discontinued OAC, 6 (13.0%), 32 (18.5%), 48 (13.2%), and 106 (10.5%) had AF recurrence and 0 (0%), 1 (2.3%), 0 (0%), and 1 (2.2%) had a stroke in CHA2DS2-VASc 0, 1, 2, and ≥3 groups, respectively. The most common reasons for discontinuation were patient preference, contraindications, and physician-patient shared decision-making. OAC was discontinued in approximately 20% of all patients undergoing catheter ablation at 1 year. Of these, roughly half had an ongoing indication for OAC. On the other hand, approximately half of patients with very low thromboembolic risk remain on OAC despite no evidence of AF recurrence.Tabled 1Table 1CHA2DS2-VASc0 (n=34)1 (n=133)2 (n=215)≥3 (n=518)Anticoagulation off (%)64.746.622.310.6AF Recurrence (%)17.624.122.520.6Stroke/TIA (%)01.01.22.2All-cause death (%)00.80.92.7Any bleeding (%)00.80.91.3 Open table in a new tab

Lenalidomide maintenance following high-dose therapy and autologous haematopoietic stem cell transplantation in chemo-resistant or high-risk non-Hodgkin lymphoma: A phase I/II study.

Improved maintenance treatments are needed for patients with relapsed/refractory aggressive lymphomas after autologous haematopoietic stem cell transplantation (ASCT). Several studies with lenalidomide have been found to have activity in the treatment of relapsed/refractory aggressive lymphomas. In the present phase I/II, single-arm, open-label study, 59 patients with high-risk relapsed non-Hodgkin lymphoma received pretransplant BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide once daily on Days 1-21 (28-day cycles) beginning at post-transplantation Day 100. The most common histologies were mantle cell lymphoma (56%) and diffuse large B-cell lymphoma (24%). The maximum tolerated dose in the dose-finding part of the study was 15 mg, but cytopenias led to the subsequent adoption of a 10 mg dose in the final study. Sixteen patients (27%) completed 12 cycles of lenalidomide maintenance. The most common reason for discontinuation was adverse events (31%). These were primarily haematologic, and 56% of patients experienced Grade 3-4 events. Two-year PFS rates (95% CIs) were 70% (56%-80%), 45% (19%-68%) and 81% (66%-90%); 2-year OS rates (95% CIs) were 91% (80%-96%), 93% (61%-99%) and 90% (76%-96%) in all patients, patients completing and patients not completing 12-month maintenance respectively. These results do not support the use of lenalidomide maintenance in this setting.

P131 Time to Discontinuation and Effectiveness with Baricitinib in Rheumatoid Arthritis: 12-Month European Data from a Multinational, Prospective, Observational Study

Abstract Background/Aims RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time-to-discontinuation of initial RA treatment. Baricitinib (BARI), an oral selective JAK1/2 inhibitor, is approved for the treatment of adults with moderate-to-severe active RA. This analysis reports time-to-discontinuation and effectiveness in patients with RA enrolled in Europe following 12M of either BARI, a biologic (b) disease-modifying anti-rheumatic drug (DMARD) or any other targeted synthetic (ts)DMARD, after starting that treatment for the first time. Methods Two cohorts were assessed: patients in cohort A initiated treatment with BARI (2-mg or 4-mg as monotherapy or in combination with any csDMARD) while patients in cohort B initiated any bDMARD (tumour necrosis factor inhibitors [TNFi] or non-TNFi bDMARD) or any other tsDMARD for the first time. Treatment initiation and changes were at the discretion of patient or physician. Time-to-discontinuation for patients in both cohorts were analysed in both bDMARD-naïve and -experienced patients. Response rates for remission and low disease activity (LDA) were determined using the Clinical Disease Activity Index at 12M. Steroid use was collected for both cohorts. This pre-specified interim analysis reports descriptive 12M data using summary statistics, without any inferential testing. Results At 12M, a similar percentage of patients discontinued 2-mg (25.4%) and 4-mg (26.9%) BARI whether as monotherapy (24.7%) or as combination therapy with any csDMARD (28.8%). In cohort B, 42.2%, 44.7%, and 52.3% of patients using TNFi, non-TNFi, and any other tsDMARD, respectively, discontinued treatment at 12M. In both cohorts, patients naïve to b/tsDMARD were least likely to discontinue treatment while those who had more than two previous b/tsDMARD treatments were most likely to discontinue. The most common reasons for discontinuation were primary non-response (Cohort A: 6.3%; Cohort B: TNFi: 8.3%, non-TNFi: 10.6%, any other tsDMARD: 10.6%) and adverse events (Cohort A: 6.3%; Cohort B: TNFi: 5.1%, non-TNFi: 7.5%, any other tsDMARD: 13.6%). At 12M, remission rates were 21.8%, 18.0%, 4.0%, and 18.2% for those on monotherapy treatment with BARI, TNFi, non-TNFi, and any other tsDMARD, respectively. For combination therapy, remission rates were 26.2%, 19.0%, 15.9%, and 13.6% for BARI, TNFi, non-TNFi, and any other tsDMARD treated patients, respectively. At 12M, 31.8% and 36.0% of patients in cohort A and B, respectively, reported ongoing steroid use, a reduction of 25.9% and 18.0%, respectively, from baseline. Conclusion Despite an older and more bDMARD experienced population, discontinuation rates were lower while remission was higher for those treated with BARI than those in cohort B. Discontinuation rate was consistent irrespective of BARI dose or if used in monotherapy or combination therapy. Discontinuation rates increased with number of previous b/tsDMARD in both cohorts, with numerically lower discontinuation rates at 12M for patients treated with BARI. Disclosure R. Alten: Grants/research support; R. A. has been a consultant for and/or received grant/research support from: AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. G.R. Burmester: Consultancies; G. R. B. has been a consultant for and/or received honoraria as a speaker for: AbbVie, Eli Lilly and Company, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB. M. Matucci-Cerinic: Corporate appointments; M. M-C. has been an officer or board member for: Biogen. Consultancies; M. M-C. has been a consultant for: Behring, Chemomab, Janssen, and Pfizer. Honoraria; M. M-C. has received honoraria as a speaker for: Eli Lilly and Company, and Sandoz. Grants/research support; M. M-C. has received grant/research support from: Merck, and MSD. A. Ostor: Consultancies; A. O. has been an advisor, review panel member, and/or consultant for: Abbot, AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Gilead, Janssen, Novartis, Paradigm, Pfizer, Roche, and UCB. L. Zaremba-Pechmann: Other; L. Z-P. is a contractor for: HaaPACS GmbH. T. Treuer: Shareholder/stock ownership; T. T. is an employee and shareholder of: Eli Lilly and Company. K. Ng: Shareholder/stock ownership; K. J. N. is an employee and shareholder of: Eli Lilly and Company. J. Gerwien: Shareholder/stock ownership; J. G. is an employee and shareholder of: Eli Lilly and Company. K.A. Gibson: Consultancies; K. A. G. has been a consultant for: Janssen, and Novartis. Shareholder/stock ownership; K. A. G. is an employee and shareholder of: Eli Lilly and Company. Honoraria; K. A. G. has received honoraria as a speaker for: UCB. Grants/research support; K. A. G. has received grant/research support from: Novartis. B. Fautrel: Grants/research support; B. F. has received research grants from AbbVie, Lilly, MSD and Pfizer, and consultancy fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Viatris. T. Sheeran (Non-Author Presenter): None.

P014 Experience of baricitinib in a real-world population with efficacy and side effects: a South London regional analysis

Abstract Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George’s Hospital; a tertiary teaching centre and Kingston Hospital; a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently); adverse effects including side effects, rates of and reasons for discontinuation; and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. Disclosure O. Buckeldee: None. K. Biddle: None. A. Latheef: None. I. Al-Shakarchi: None. N. Sofat: None.

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy

ObjectiveEpidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. MethodsA single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. ResultsOne hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SignificanceEpidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

Atorvastatin

Atorvastatin

Long-Term Durability of Certolizumab Pegol in Patients with Rheumatoid Arthritis Over 5 Years: An Analysis of Pooled Clinical Trial Data.

There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5years between different subgroups of patients with RA. Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10years). Among 6927 patients, the durability of CZP was 39.7% at 5years. Patients aged ≥ 65years had a 33% greater risk of CZP discontinuation than patients 18- < 45years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%). CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.