Common Reason For Discontinuation Research Articles

Apremilast Survival and Reasons for Discontinuation in Psoriasis: Five-Year Experience From a Greek Tertiary Care Centre.

IntroductionDrug survival is an indirect measure of efficacy and safety and its post-marketing assessment using real-life data is invaluable.ObjectivesTo investigate the survival of apremilast in a cohort of psoriasis patients treated with apremilast in a Greek hospital.MethodsA retrospective cross-sectional study examined adult psoriasis patients receiving apremilast (March 2016 to January 2021). Primary endpoint was the cumulative survival probability at 52 weeks. Kaplan-Meier analysis was used to calculate survival probability. Cox regression analysis was performed to investigate potential risk factors for apremilast discontinuation.ResultsOne hundred and two patients (29.4% females) with a mean age of 55.9 years (standard deviation 15.21) were included. Sixty-five patients (63.7%) had discontinued treatment by lock date: 19 (18.6%) due to lack of efficacy, 24 (23.5%) due to loss of efficacy, 15 (14.7%) due to adverse reactions, and 7 (6.9%) due to other reasons. Cumulative survival probability at 52 weeks was 52.1%. Median survival time for all reasons for discontinuation was 58 weeks (95% Confidence Interval 40.02, 75.98).ConclusionsApproximately half of patients remained on apremilast after 1 year of treatment. Secondary drug failure was the most common reason for discontinuation.

PD35-07 ANALYSIS OF DISCONTINUATION RATES AND CAUSES OF EARLY DISCONTINUATION OF NOVEL ORAL HORMONE THERAPY IN MEN WITH ADVANCED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD35-07 ANALYSIS OF DISCONTINUATION RATES AND CAUSES OF EARLY DISCONTINUATION OF NOVEL ORAL HORMONE THERAPY IN MEN WITH ADVANCED PROSTATE CANCER David Gangwish, Bernadette Zwaans, Paul Miriani, Wesley Dejoie, Andrina Ajo, Connor Ervin, Jeff Sarazin, and Jason Hafron David GangwishDavid Gangwish More articles by this author , Bernadette ZwaansBernadette Zwaans More articles by this author , Paul MirianiPaul Miriani More articles by this author , Wesley DejoieWesley Dejoie More articles by this author , Andrina AjoAndrina Ajo More articles by this author , Connor ErvinConnor Ervin More articles by this author , Jeff SarazinJeff Sarazin More articles by this author , and Jason HafronJason Hafron More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002593.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the second most common cause of cancer-specific death in US men. Novel oral hormone therapy (NHT) significantly prolongs survival and maintains quality of life in advanced PCa patients. Despite known benefits, these medications are commonly discontinued. The study evaluated the prevalence of early discontinuation of NHT, the determinants of early discontinuation and the effect of changing NHT on duration of treatment. METHODS: A retrospective cohort study of 333 patients with advanced PCa who started a NHT in a single community urology practice in the United States between February 2016 and July 2020 were evaluated. NHT medication, start date of treatment, reason for discontinuation, and discontinuation date were collected. Additional data included demographics, stage of PCa, PSA at time of NHT initiation, Gleason score, and prior PCa treatments. The cohort was divided into 2 subgroups, those did not change medication (Group A) and those that did change to a different NHT (Group B). Student’s t-test, Chi-square test, and Kaplan-Meier survival analysis were carried out to determine significant differences between groups (SPSS). RESULTS: At one year 28.8% of patient’s had early discontinuation of NHT. The most common reasons for discontinuation were side effects and death at 34.4% each. Group A (282 patients) and Group B (51 patients) discontinued treatment at a rate of 31%, 88%, respectively. Primary reasons for discontinuation in group A versus group B was due to side effects (36% vs 47%) or cancer progression (34% vs 49%). More patients in group B were deceased than in group A (58.8% vs 29.4%). Of those that discontinued, patients remained on NHT for an average of 382 days in group A versus 593 days in group B (Figure 1, Kaplan-Meier analysis p = 0.003). In group B, patients on average discontinued first NHT after 330 days and continued secondary NHT for an additional 263 days. CONCLUSIONS: Side effects and cancer progression were the main reasons for discontinuing NHT treatment. Providing patients with alternative NHT significantly increases the duration of treatment. It is important for clinicians to understand the causes of early discontinuation to develop strategies to maximize duration of therapy for management of advanced PCa. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e629 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Gangwish More articles by this author Bernadette Zwaans More articles by this author Paul Miriani More articles by this author Wesley Dejoie More articles by this author Andrina Ajo More articles by this author Connor Ervin More articles by this author Jeff Sarazin More articles by this author Jason Hafron More articles by this author Expand All Advertisement PDF DownloadLoading ...

Clinical implementation of ketogenic diet in children with drug-resistant epilepsy: Advantages, disadvantages, and difficulties

PurposeKetogenic diet (KD) is a well-established nonpharmacologic treatment for drug-resistant epilepsy. However, although KD has a long history of clinical use, there are still many difficulties with its real-world practice. This study retrospectively described the situation of KD practice in two children's hospitals in Southwest China. MethodsWe reviewed and analyzed clinical data collected at the baseline, and during follow ups at 1, 3, 6, 12, 18, and 24 months. The patient retention, the efficacy, side effects of KD, and the reasons for discontinuation were focused. ResultsThere was increasing availability of KD for children with epilepsy in Southwest China and its effectiveness in controlling seizures was reconfirmed. Nonetheless, less than half of the patients adhered to KD for one year and about 1/5 of the patients for two years. Unsatisfactory seizure control was the most common reason for discontinuation, followed by patient/caregiver preference, acute infection, and loss to follow up. Adverse effects were mostly tolerable and not the main reason for discontinuation. Meanwhile, KD showed negative impacts on linear growth, and our cohort seemed to have more infections and deaths. ConclusionsDespite increasing availability and good efficacy, long-term adherence to KD was difficult. Compliance issues appeared to be prominent. Enhancing food taste and patient support can help to improve the retention rate.

Why Do HIV Pre-Exposure Prophylaxis Users Discontinue Pre-Exposure Prophylaxis Care? A Mixed Methods Survey in a Pre-Exposure Prophylaxis Clinic in Belgium.

It remains unclear why patients discontinue HIV pre-exposure prophylaxis (PrEP) care and to what extent they remain at risk for HIV when they do. We reviewed routinely collected medical records and patient questionnaires and performed an e-mail/telephone survey to assess reasons for discontinuing PrEP care, ongoing risks for HIV infection, and associated factors. Patients with more than two registered PrEP visits from a PrEP clinic in Antwerp, Belgium between June 2017 and February 2020 were included in this study. Patients who did not return for a visit after October 30, 2019 and who were not transferred out were considered as having discontinued PrEP care. A total of 143/1073 patients were considered as having discontinued PrEP care. Patients who discontinued PrEP care were more likely to be younger than those who remained in care (35 vs. 38 years old, p < 0.01). The most common reasons for discontinuation were having stopped using PrEP (62/101, 61.4%) and “COVID-19” (n = 35, 34.7%). The most common reasons for stopping PrEP use was a decreased sexual activity due to coronavirus disease 2019 (COVID-19; 21/62, 33.9%) or not COVID-19 related (10/62, 16.1%), a monogamous relationship (20/62, 32.3%) and consistent condom use (7/62, 11.3%). Among respondents who reported about current HIV risk the majority reported being at low risk either by still taking PrEP (32/91, 35.2%), consistently using condoms, or limiting number of sex acts or partners (58/91, 52.7%). No HIV seroconversion was reported.

Real-world 2-year long-term outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic squamous cell carcinoma of the head and neck

ObjectiveReal-world outcomes and prognostic factors in Japanese patients receiving nivolumab therapy for recurrent or metastatic head and neck carcinoma (RMHNC) with an observation period of 1 year have been previously reported. The 1-year follow-up data have been subsequently accumulated, and the long-term real-world outcomes have been analyzed. This study aimed to investigate the 2-year long-term outcomes and prognostic factors associated with the response to nivolumab. MethodsThis was a multi-institutional retrospective study. In total, 88 RMHNC Japanese patients with squamous cell carcinoma who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and best overall response (BOR) were evaluated. Univariate and multivariable analyses were performed to identify the prognostic factors. ResultsThe median follow-up periods for monitoring OS and PFS were 73.1 and 48.1 weeks, respectively. The median OS was 74.1 weeks, and the 2-year survival rate was 33.4%. The median PFS was 18.5 weeks, and the 2-year PFS rate was 22.5%. The BOR rate was 10.2%, 19.3%, 25.0%, and 44.3% in patients who achieved complete response, partial response, stable disease, and progressive disease (PD), respectively. Among the 88 patients with RMHNC, a total of 40 immune-related adverse events (irAEs) were reported in 30 patients. Four patients continued nivolumab, while 84 patients discontinued nivolumab at the data cut-off date. The most common reason for discontinuation was PD in 61 patients, irAEs in 14 patients, and patients’ wishes in 7 patients. Of the 61 patients who discontinued nivolumab because of PD, 28 patients received subsequent treatment. Statistical analyses revealed radiotherapy history, performance status, platinum-refractory carcinoma, irAEs, age, and post-nivolumab treatment as the important prognostic factors associated with OS in patients with RMHNC, and the magnitude of BOR was significantly associated with OS. Additionally, patients with subsequent treatment, including molecular targeted therapy and/or chemotherapy, had significantly prolonged OS compared to patients without subsequent treatment in cases with nivolumab discontinuation because of PD. ConclusionThese findings could be a useful guide for future treatment strategies for head and neck carcinoma. Considering the limitations of our cohort, further larger-scale studies with long-term follow-up are needed to substantiate the results of this study.

Dupilumab for the treatment of atopic dermatitis: real-world data from the Czech Republic BIOREP registry

Background Dupilumab has been approved to treat moderate-to-severe atopic dermatitis; however, the data in a real-world setting are still limited. Objective To analyze the effectiveness and safety of dupilumab. Methods This was a real-life Czech multicenter retrospective study from patients treated with dupilumab for severe AD. Results A total of 360 patients were included. At 16 weeks, 66.6, 34.1, and 5.5% of patients achieved EASI75/90 and EASI100, respectively. Improvement continued with the time, and the proportion of patients with EASI75/90 and EASI100 increased to 89.5, 55.6, and 12.9% after one year of treatment and reached 95.8, 60.4, and 27.1% in the second year of therapy, respectively. A significant reduction was observed in the DLQI scores. The most common adverse events were infections in 5.8% of patients, followed by ocular complications in 2.5% of patients. Persistence rates were 98.2% at four months to 93.1% at month 24, and lack of effectiveness was the most common reason for discontinuation. Conclusion This real-life study confirmed the effectiveness and safety of dupilumab in a real-life setting during the COVID-19 pandemic. Our study revealed a higher frequency of infections and a lower conjunctivitis frequency than other real-life studies and clinical trials.

A149 REAL WORLD OUTCOMES OF NON-MEDICAL SWITCHING OF INFLIXIMAB BIOSIMILAR IN BRITISH COLUMBIA FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE (IBD)

Abstract Background A mandated non-medical switch to the infliximab biosimilars was launched in British Columbia in 2019. British Columbia was the first province in Canada to mandate the switch from the originator infliximab (RemicadeTM) to one of the 2 approved biosimilars (InflectraTM or RenflexisTM). There is limited data for mandatory non-medical switching in IBD as was undertaken in BC. Aims This study aimed to obtain real-world evidence evaluating the clinical outcomes of nonmedical switch from Remicade to the infliximab biosimilars. Methods This is a retrospective observational study from the IBD Centre of BC (a tertiary care referral centre in Vancouver, BC). Patients on infliximab at the time of the mandated switch were identified through search of the electronic medical record. The primary outcome was drug continuation at 12 months post switch. Secondary outcomes included flare of disease, adverse events, and number of doctor visits within the first 12 months post switch. A comparison group included patients maintained on originator infliximab. Results A total of 235 patients were evaluated; 175 patients in the biosimilar switch group, and 60 patients in the control group. Baseline characteristics of the groups were similar. Discontinuation of infliximab occurred in 22 patients (17 in biosimilar switch group and 5 in the control group. There was no difference in the rate of discontinuation of infliximab between the biosimilar group (9.7%) and the originator molecule group (8.3%); chi squared (1, N=235) = 0.1004, p = .75. The most common reason for discontinuation was flare of disease in 6 patients in the biosimilar group and 4 patients in the control group. An additional 4 patients in the biosimilar group and 3 patients in the control group had a flare of symptoms but were maintained on therapy with an escalation of dosage or course of corticosteroids. Two patients had active disease at the time of switch and discontinued therapy. Adverse events accounted for discontinuation in 5 patients on biosimilar and 1 in the control group. These included joint pain, epigastric symptoms, drug intolerance, drug induced lupus, and drug induced pulmonary nodules in the biosimilar group, and drug induced vasculitis in the control group. Two patients in the biosimilar group discontinued due to antibody formation. Two patients in the biosimilar group discontinued therapy due to preference. Conclusions In this small subset of the BC IBD population undergoing a non-medical biosimilar switch of infliximab, there was no difference in the discontinuation rate between the biosimilars or the originator infliximab molecule. These findings are consistent with the existing real-world evidence. Funding Agencies None

Daily Oral Pre-exposure Prophylaxis (PrEP) Continuation Among Women from Durban, South Africa, Who Initiated PrEP as Standard of Care for HIV Prevention in a Clinical Trial

HIV incidence among women in Eastern and Southern Africa remains unacceptably high, highlighting the need for effective HIV prevention options, including pre-exposure prophylaxis (PrEP). The Evidence for Contraceptive Options and HIV Outcomes trial offered daily oral PrEP to participants during the latter part of the clinical trial as an additional HIV prevention choice. We explored daily oral PrEP continuation at trial exit among women enrolled from Durban, South Africa who initiated oral PrEP at the trial site. Of the 132 women initiating oral PrEP, 87% reported continuation of oral PrEP at month 1, 80% at month 3, and 75% continued using oral PrEP at their final trial visit and were referred to off-site facilities for ongoing oral PrEP access. The median duration of oral PrEP use in trial participants who used oral PrEP was 91 days (IQR 87 to 142 days). Women who disclosed their oral PrEP use to someone had increased odds of continuing oral PrEP at trial exit. Women who reported > 1 sex partner and those who felt they would probably or definitely get infected with HIV had reduced odds of continuing oral PrEP at trial exit. Of those discontinuing oral PrEP (n = 32), > 50% discontinued within the first month, and the most common reason for discontinuation was reporting side effects. The high rates of oral PrEP continuation in our study are encouraging and our findings can be utilized by other clinical trials providing oral PrEP as standard of care for HIV prevention and by oral PrEP implementation programmes.

Phase I/II study of regorafenib (rego) and pembrolizumab (pembro) in refractory microsatellite stable colorectal cancer (MSSCRC).

15 Background: Immune check point inhibitors (ICI) are ineffective in MSSCRC. Combination of ICI with targeted agents has the potential to alter the tumor microenvironment and render these tumors vulnerable to ICI. We report the results of the multicenter study of rego and pembro in a diverse patient population with advanced MSSCRC. Methods: This was an investigator-initiated study and enrolled patients (pts) who had failed/were intolerant of chemotherapy at 3 sites. A 3+3 design was used for phase I to evaluate escalating doses of rego (80,120,160, days 1-14/21) in combination with pembro (200m/q3weeks). The primary endpoint was dose limiting toxicities during the first cycle. For phase II, pts received rego at the recommended phase II dose (RP2D) with pembro. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS) and objective response rate (ORR). The study was powered to show an improvement in PFS from 1.9 months (CORRECT data) to 2.85 months. Estimated sample size for phase II was 63 pts. Results: Study started in 7/2019 and accrual completed in 7/2021. Of 73 pts, 10 enrolled in phase I and 63 in phase II. RP2D of rego was 80 mg, days 1-14/21, and 70 pts treated at that dose. As of Sep 14, 11 pts remain on treatment. At baseline, median age was 54 years (23-81), 51% female, 53% white, 19% Asian, 12% black, and 11% Hispanic, median prior lines of therapy 2 (1-5), primary tumor location rectosigmoid/rectal 13%, KRAS mutated 68%, BRAF mutated 5%. Liver metastases was present in 78% of the pts. There was no grade 4 toxicity. The most common grade 3 toxicities were rash (20%), followed by hand-foot syndrome and HTN (7%). Dose modification was required in 14%. The most common reason for discontinuation was disease progression (85%), followed by withdrawal of consent (12%). With a median follow up of 5.3 (range:0.6-24.4) months, median PFS was 2.0 (1.8 -3.5) months, and median OS was 10.9 (5.3-NR) months. In 16 pts (23%), with non-liver metastatic disease PFS was 4.3 (1.9-8.4) months. No objective response was observed. Stable disease was observed in 49% of pts, median duration of stable disease was 2 (0.2-18.8) months. Conclusions: This is the largest trial of combination of ICI + rego in MSSCRC reported to date. The trial didn’t meet its primary endpoint, though the median OS is provocative. Analysis of biomarkers for identification of pts with longer duration of benefit is ongoing. Clinical trial information: NCT03657641.

Prevalent Drug Usage Practices in Adults and Children With Idiopathic Inflammatory Myopathies: Registry-Based Analysis From the MyoCite Cohort.

Idiopathic inflammatory myopathies (IIMs) form a heterogeneous group of disorders with a deficit of quality evidence regarding its management. Therefore, we aimed to explore the prevalent treatment practices in the MyoCite cohort from India. Drug usage patterns, their predictors, drug retention rates, efficacy, and adverse drug reactions were analyzed for adults and children newly diagnosed with IIM (2017-2020) and followed prospectively and compared with real-world data by performing a medical records review. GraphPad Prism version 8.4.2 was used for statistical analysis. Of 181 adults (male-to-female ratio, 1:4.6) and 30 children (M:F, 1.3:1), dermatomyositis (41% adults, 93% children) was the most common subtype. Methotrexate (MTX) was the drug of choice (67% adult, 90% children) followed by azathioprine (AZA) and mycophenolate mofetil (MMF). The MMF, AZA, cyclophosphamide, and rituximab (RTX) were preferred for those with antisynthetase syndrome (ASSD) and those with lung involvement, whereas MTX was avoided in them. Functional class and family income did not determine drug preferences. Glucocorticoids were initiated at a lower dose in overlap myositis (45% vs 80%, p = 0.001), and the time to achieve the lowest dose of glucocorticoids was longer than 24 months for ASSD (77% vs 14%, p = 0.002).Over a median of 35 months, the overall retention rate was the highest for RTX (75%) followed by MTX (58%). Relapse-free survival was the highest for RTX followed by MTX. The most common reasons for discontinuation were adverse drug reactions for MTX and MMF, inefficacy for AZA, and cost for RTX. In this first analysis of drug usage and retention in patients with IIM in Northern India, MTX emerged as the most preferred drug in both adults and children, with the exception of those with ASSD or lung disease. Organ involvement and subtype of IIM are key determinants of drug preference. Overall, RTX and MTX were well-tolerated with high retention rates, followed by AZA and MMF.

LONG TERM OUTCOMES OF PARTIAL ENTERAL NUTRITION THERAPY IN CHILDREN WITH CROHN’S DISEASE

Abstract BACKGROUND Partial enteral nutritional therapy (PEN, defined as 80% of daily caloric intake from formula) has shown similar efficacy in inducing remission for pediatric Crohn’s Disease (CD) in comparison to exclusive enteral nutrition (EEN, defined as 100% of daily caloric intake from formula). Long-term outcomes of PEN are not well defined in the literature We aimed to study the long-term outcomes of PEN as defined by the number of patients still on maintenance PEN at 1 and 2 years after initiation. METHODS This was a retrospective cohort study using electronic medical record data at a large pediatric academic center. Patients diagnosed with CD between ages 7-19 years at PEN initiation with available follow-up data were included. Exclusion criteria were diagnoses of ulcerative colitis or indeterminate colitis, concomitant treatment with systemic steroids (prednisone (or equivalent) dose &amp;gt; 20 mg daily), biologics, or immunomodulators. Data collected included demographic and IBD characteristics as well as details of PEN therapy. We calculated the one and two-year PEN persistence rates and used Kaplan-Meier methods to produce survival curves of PEN persistence with adjustment for censoring. RESULTS Between 2009 and 2021, forty-nine participants met inclusion criteria (out of 114 assessed for inclusion). Participants were mostly white (n = 38, 77%), and male (n = 30, 61%). The mean age at CD diagnosis was 11.4 years (standard deviation, SD: 2.9 years) and the mean age at PEN initiation was 12.1 years (SD: 2.6 years). The most common reasons for PEN initiation were primary induction (n = 30, 61%), family/patient preference to avoid other medications (n = 26, 53%), and failure of primary medical therapy (n = 10, 20%). The most chosen formula type for PEN therapy was partially hydrolyzed formulas (n = 30, 61%), followed by standard formulas with whole intact proteins (n = 16, 33%). The one-year PEN persistence rate was 51% (26/49) and the two-year persistence rate was 25% (12/49) (table1). The median time on PEN was 1.3 years (IQR: 0.6 – 2.2 years) (Figure 1). The most common reasons for discontinuation were disease relapse/progression (n=32/41,78%) and treatment non-adherence (n =8/41, 20%). A small number of individuals discontinued due to formula intolerance (n = 3/41,7%). The most common medical therapies escalated to were infliximab (n =21/41, 51%), and adalimumab (n = 8/41, 20%) when PEN was discontinued. DISCUSSION Our study suggests that PEN therapy can be used as potential long-term treatment strategy for mild pediatric Crohn’s disease while avoiding corticosteroids and side-effects common with other IBD therapies. Secondary analysis is underway to understand predictors of response or failure to PEN therapy such as disease location/ distribution, type of formula, and the amount of calories from food vs. formula.

DOP44 Long-term use of ozanimod in patients with moderately to severely active Ulcerative Colitis

Abstract Background Ozanimod was approved by the FDA to treat patients (pts) with moderately to severely active Ulcerative Colitis (UC) based on the results from the 52-week (wk) phase 3 True North (TN) study. We sought to evaluate long-term efficacy and safety of ozanimod. Methods We examined data from an interim analysis of pts in the TN parent study who entered the ongoing TN open-label extension (OLE). Pts entered the TN OLE from the phase 3 TN study if they were non-responders at the end of induction, lost response during maintenance, or completed maintenance treatment, or from the phase 2 Touchstone OLE if they remained at study closure and received once-daily oral ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg). Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at Wks 46, 94, and 142 in the TN OLE for all pts who entered the OLE from the TN parent study, and in the subset of pts in clinical response at the OLE entry. The data were analysed in the intent-to-treat population using observed cases (OC), which used the number of pts remaining in the study at the corresponding time point, and non-responder imputation (NRI), which used the number of pts remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed. Treatment-emergent adverse events were evaluated from the pooled phase 2 and phase 3 UC studies. Results A total of 823 pts from TN entered the TN OLE; as of the cut-off date (Sept 30, 2020), 64% completed Wk 46, 34% completed Wk 94, and 14% completed Wk 142 of the OLE. The most common reason for discontinuation was lack of efficacy (21%). Baseline demographics were similar as in the TN study. A total of 261 pts were in clinical response at the time of OLE entry. OC analyses showed that the percentage of pts achieving clinical remission, clinical response, endoscopic improvement, and CS-free remission was maintained over time (Table). Efficacy in the responders was higher compared to the total population and was comparable within the endpoints at Wks 46 and 94. Using the more conservative NRI analysis, the proportion of pts achieving each endpoint was lower than in the OC; however, after 94 wks of OLE treatment, 34% of all pts and 55% of the responders still maintained clinical response. No new safety signals were seen with longer-term ozanimod use in the 1158 pts in the pooled population. Conclusion UC pts from the phase 3 TN study demonstrated maintenance of response with long-term ozanimod treatment. These data reflect approximately 2 years of additional ozanimod treatment, with no new safety signals identified.

Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey.

Introduction: Endometriosis affects 1 in 10 women worldwide, with most experiencing difficulties achieving adequate symptom control. These difficulties have been compounded by the onset of the COVID-19 pandemic due to worldwide shifts in health care resource allocation. As cannabis is a relatively common form of self-management in endometriosis, this study aims to explore the impact of the COVID-19 pandemic on cannabis consumption in those with endometriosis. Methods: An anonymous, cross-sectional online international survey was developed and promoted by endometriosis advocacy/support organizations worldwide. Respondents needed to have a diagnosis of endometriosis and be aged between 18 and 55. Results: A total of 1634 responses were received from 46 different countries. The average age of respondents was 30, with a mean diagnosis age of 25. Eight hundred forty-six respondents (51%) reported consuming cannabis in the past 3 months, with 55% of these reporting use for symptom management only. One in five respondents (20%) reported having consumed cannabis previously, the most common reason for discontinuation (65%) was access difficulties during COVID. Those who had legal access were more likely to consume cannabis than those without (p<0.0001) and were more likely to disclose usage to health care professionals (p<0.0001). The most common reasons for consuming cannabis during COVID was increased stress/anxiety (59%) and lack of access to normal medical care (48%). Pre-pandemic, cannabis was mostly consumed at least once a day (61%) and in inhaled forms (51.6%). Consumption increased for most people (57%) during the pandemic. During the pandemic just under a quarter (23%) of respondents changed their mode of consumption, with a reduction in inhaled forms (39.5%) and an increase in consumption of edibles (40%) or oil (25.2%). Conclusions: Cannabis consumption, especially for symptom relief, was relatively common among those with endometriosis, with some people starting their consumption of cannabis due to health care restrictions that occurred due to the COVID-19 pandemic. Difficulties accessing cannabis and unpleasant/unwanted side effects were the most common reasons for lack of current cannabis consumption in those who had previously consumed it. Cannabis consumption may form an important part of endometriosis management especially when access to routine medical care is restricted.

Five-year Follow-up of Patients With Head and Neck Cancer Treated With Nivolumab and Long-term Responders for Over Two Years.

A long-term effect has been confirmed in clinical practice since the introduction of nivolumab for treating various malignant tumors. A similar phenomenon is speculated to occur in head and neck cancer; however, details remain unclear due to the lack of long-term reports. We aimed to investigate the five-year outcomes in long-term responders for over two years, and evaluate the optimal duration of therapy with nivolumab. In this retrospective observational study, we analyzed 203 cases of recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), including 33 long-term responders. The median overall survival (OS), 5-year OS, median progression-free survival (PFS), and 5-year PFS values in the 203 cases were 13.1 months, 19.2%, 3.1 months, and 13.2%, respectively. Of the 33 long-term responders, 14 (42.4%) continued using nivolumab for more than 2 years. The remaining 19 patients (57.6%) discontinued nivolumab. The most common reason for discontinuation was severe immune-related adverse events (irAEs) (9 cases; 27.3%); in these 9 cases, the median disease-free survival was 33.2 (range=10.7-44.3) months. Nine patients (21.2%) were considered to have progressive disease (PD) after at least 2 years of administration, and 3 patients (9.1%) requested to discontinue treatment because a complete response (CR) was achieved. This study demonstrated the durable and long-term benefit of nivolumab in R/MHNSCC. In the future, we aim to accumulate real-world data for the establishment of criteria for completion of nivolumab treatment in long-term responders.

Natural history and patterns of treatment change in Parkinson’s disease: A retrospective chart review

BackgroundParkinson’s disease (PD) management seeks to balance the benefits and harms of current medications and evolves as the disease progresses. The natural history of PD and associated patterns of treatment change were analyzed to identify unmet needs in treatment of PD symptoms. MethodsMedical charts of patients from clinics across the US diagnosed on or before June 30th, 2014 were retrospectively reviewed. Index date was the first clinic visit, and the post-index period was through study end (June 30th, 2019). Outcomes included the frequency of therapy changes in the post-index period, reasons for therapy change, and adverse events (AE). ResultsPatients (n = 203) at index were receiving levodopa-peripheral dopa decarboxylase inhibitor (PDDI) monotherapy (47%), dopaminergic agonist (DA) monotherapy (15%), monoamine oxidase B inhibitor (MAOBI) monotherapy (14%), or combination therapies. The percentage of patients in Hoehn-Yahr disease Stage 1–2 was 52% at index and 20% by the end of the study. Frequencies of motor, non-motor, and neuropsychiatric symptoms increased during the enrollment. Levodopa-PDDI monotherapy and levodopa-PDDI + MAOBI had the lowest rates of therapy changes. Symptom relapse was the most common reason for dose escalation, add-on, and dose reduction, whereas AEs were the most common reason for discontinuation and switching. Dose escalation, add-on, and forward switch were most likely to occur in the first 6 months of treatment. ConclusionsTherapy changes during the study period reflected the challenging and evolving management of PD as the disease progresses. New or add-on symptomatic treatments are needed that are well-tolerated and able to control PD symptoms.

859. Suboptimal Uptake, Retention, and Adherence of Daily Oral PrEP Among People with OUD Receiving HCV Treatment

BackgroundDaily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) effectively prevents HIV among people who use drugs (PWUD). Despite rising rates of HIV incidence and injection drug use, PrEP use remains low and limited research exists on PrEP adherence and retention in this population.MethodsBased in Washington, DC and Baltimore, the ANCHOR investigation evaluated a community-based model of care collocating hepatitis C (HCV) therapy, medication for opioid use disorder (OUD), and PrEP in people with chronic HCV, OUD, and drug use within 1 year. PrEP counseling was offered from HCV treatment Day 0 until Week 24 and subjects could start any time during this window. PrEP patients were followed for 48 weeks and assessed for adherence by self-report and dried blood spot analysis of TDF. ANCHOR PrEP study enrollment and participant retention along the PrEP continuum.Results198 participants enrolled in ANCHOR, of whom 185 (93%) were HIV-negative. 29 subjects (16% of HIV-negative group) initiated PrEP. 116 subjects (63%) met 2014 CDC criteria for PrEP initiation due to IDU (82, 44%), sex (9, 5%), or both (25, 14%). Those who initiated were more likely to meet both CDC sexual and IDU risk criteria than those who declined PrEP (P=0.006). Providers recommended PrEP to 94 subjects (51%), which was associated with uptake (P=0.02). While median treatment duration was 104 days (IQR 28, 276), only 8 subjects were retained through Week 48. The most common reason for discontinuation was side effects in 7 subjects or 24% of PrEP subgroup. Treatment interruptions occurred in one-third of the PrEP subgroup. Adherence of 4 to 7 pills per week was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Demographic and epidemiological background of the ANCHOR study population. Total duration, in days, on PrEP in the ANCHOR study. Discontinued participants are grouped by reason for cessation of therapy.PrEP Adherence Adherence to PrEP by ANCHOR study timepoint, assessed via self-report (above) and dried bloodspot analysis of tenofovir level (below).ConclusionIn this cohort of people with OUD and HCV, 16% of subjects started PrEP. While clinical recommendation was associated with uptake, high rates of disruption and discontinuation, compounded by variable pill adherence, made daily oral TDF/FTC a suboptimal preventive strategy in this cohort. Emerging PrEP modalities like long-acting injectables have potential to address these barriers, but PWUD have been excluded from their research and development to date. Additional work to identify vulnerable individuals and to promote use, adherence, and retention will be critical in implementing PrEP more effectively in this key population.Disclosures Sarah Kattakuzhy, MD, Gilead Sciences (Scientific Research Study Investigator, Research Grant or Support) Elana S. Rosenthal, MD, Gilead Sciences (Research Grant or Support)Merck (Research Grant or Support)

Long-term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program.

ObjectiveWe determined retention on open‐label cenobamate therapy in the clinical development program to assess the long‐term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.MethodsData from two randomized, controlled cenobamate studies and one open‐label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan‐Meier survival analyses. We performed two additional analyses to assess factors contributing to retention, stratifying a robust data set (through 2 years) by cenobamate modal dose and frequently used concomitant anti‐seizure medications. Cenobamate discontinuations and treatment‐emergent adverse events were summarized.ResultsData from 1844 participants were pooled: 149 from a single‐dose randomized trial, 355 from a multi‐dose randomized trial, and 1340 from an open‐label safety and pharmacokinetic study. Most participants from randomized trials continued in open‐label extensions, and pooled data represent >95% of participants exposed to cenobamate. Baseline characteristics and disease and treatment histories were similar across studies. Median duration of cenobamate exposure was 34 months, with a median modal dose of 200 mg/day. Kaplan‐Meier estimates of cumulative cenobamate retention rates were 80% at 1 year and 72% at 2 years. Once participants reached the maintenance phase, retention rates were consistently high in participants receiving ≥100 mg/day cenobamate, and concomitant anti‐seizure medications did not affect long‐term retention. By 2 years, 535 (29%) had actually discontinued cenobamate; the most common reasons for discontinuation were adverse events (37.6%), withdrawal of consent (21.1%), and other (16.8%).SignificanceTreatment retention rates provide a proxy measure for long‐term efficacy, safety, tolerability, and adherence. The consistently high retention rates we found suggest that cenobamate may be an effective and well‐tolerated new treatment option for people with drug‐resistant focal seizures.

Abstract 9672: Antiplatelet Therapy and Covid-19 Outcomes in Patients With Stable Coronary Artery Disease

Introduction: Severe COVID-19 can cause acute respiratory distress syndrome (ARDS), with pulmonary pathology composed of platelet microthrombi. Antiplatelet agents have been investigated as a treatment in ARDS, but without clear evidence of benefit. The decision on antiplatelet use in patients with COVID-19 and coronary artery disease (CAD) is key. Hypothesis: We assessed the hypothesis that increased use of antiplatelet therapy was associated with no worse clinical outcomes in COVID-19 among adults with stable CAD. Methods: We performed a retrospective cohort study of patients who presented with COVID-19 to two New York City hospitals from March 3 to May 15, 2020. Patients were separated into groups based on antiplatelet use, including no outpatient antiplatelet use, monotherapy, and dual antiplatelet therapy (DAPT). Outcomes and complications were compared among the groups, using propensity scoring with inverse probability of treatment weighting. Results: This study included 315 patients with stable CAD and COVID-19. Patients on no outpatient antiplatelet therapy were significantly older and more likely to be taking anticoagulation, while patients on DAPT had the highest rates of diabetes and chronic kidney disease. The most prescribed antiplatelet in the cohort was aspirin (72.1%) followed by clopidogrel (22.5%). There was no difference in COVID-19 admission mortality between the DAPT and monotherapy groups (DAPT 27.9%, monotherapy 27.2%, p=NS). Patients on DAPT had decreased rates of venous thromboembolism compared to monotherapy (DAPT 0.0%, monotherapy 6.4%, p=0.01), and bleeding rates were similar. The rate of home monotherapy continuation in hospital was 79.9%, with the most common reasons for discontinuation being hemorrhage, anemia, and thrombocytopenia. No outpatient antiplatelet use was a high-risk group, with the highest rates of intensive care admissions, intubations and mortality. Conclusions: In conclusion, we found no difference in COVID-19 outcomes for CAD patients on DAPT compared to those on monotherapy. There were decreased clotting complications in patients on more antiplatelet therapy, while bleeding rates were similar. No outpatient antiplatelet use was found to be a high-risk group in COVID-19.

Real-World Evaluation of the Treatment Landscape for Chronic Lymphocytic Leukemia

Introduction:The treatment paradigm of chronic lymphocytic leukemia (CLL) has changed significantly with the introduction of targeted oral therapies, including Bruton's tyrosine kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitors (Bcl-2is). As more therapies enter the clinic, real-world data (RWD) are important to understand changes in the CLL treatment landscape and describe treatment patterns, to guide decisions on treatment strategies.Methods:This retrospective analysis used 2 RWD sources. Patients (pts) diagnosed with CLL and treated with chemotherapy, CD20 monoclonal antibodies (mAbs), BTKis, or Bcl-2is were studied in the Optum Clinformatics® Data Mart (CDM), a de-identified US administrative claims database. Pts in the CDM analysis received at least 1 prescription for or administration of a treatment of interest between 2016 and 2020 Q2, and a diagnosis of CLL within 12 months (mo) of treatment start. Cross-sectional annual cohorts were used to understand changes in treatment mix over time, and longitudinal cohorts were formed to identify treatment patterns. Medication adherence was assessed with persistence at 12 mo using a 60-day gap and proportion of days covered (PDC) at 12 mo. Electronic health records from oncology practices were extracted through December 2020 from the COTA real-world evidence database. Adults diagnosed with CLL/small lymphocytic lymphoma and treated with BTKis and/or Bcl-2is were included. Treatment discontinuation was assessed using physician-documented treatment dates and reasons for discontinuation, and overall duration of treatment with targeted therapy was assessed using Kaplan-Meier analysis.Results:In CDM, annual treatment rate among pts diagnosed with CLL increased from 16% (1788/10911) in 2016 to 26% (2441/9349) in 2020. The proportion of pts treated with BTKis and Bcl-2is increased from 40% (2016) to 65% (2020) and <1% (2016) to 13% (2020), respectively; corresponding decreases in the use of chemotherapies and CD20 mAbs were observed (Figure 1A). In pts initiating BTKis, most pts were not previously treated (937/1438; 65%); the most common initial regimens were BTKi monotherapy (mono) (1367/1438; 95%) and BTKi + CD20 mAb (54/1438; 4%). Few pts switched from BTKi mono to CD20 mAb mono (43/1367; 3%) or added CD20 mAb to BTKi mono (44/1367; 3%) within 12 mo. In pts initiating Bcl-2is, most received prior treatment (169/198; 85%); most common regimens were Bcl-2i mono (159/198; 80%), Bcl-2i + CD20 mAb (31/198; 16%), and Bcl-2i + BTKi (8/198; 4%). Among pts initiating Bcl-2i mono, 30% (48/159) added CD20 mAb within 12 mo; among pts initiating Bcl-2i + CD20 mAb, 94% (29/31) switched to Bcl-2i mono within 12 mo. Persistence at 12 mo was similar for BTKis (899/1438; 63%) and Bcl-2is (120/198; 61%) and mean (SD) PDC was similar for BTKis 0.69 (0.31) and Bcl-2is 0.68 (0.29). In COTA, 469 pts treated with BTKis and/orBcl-2is were included. More pts initiated BTKis as first-line (1L) (185/449; 41%) compared with Bcl-2is (13/109; 12%). Among pts initiating targeted therapy as 1L, most pts (81%; 149/185) initiated BTKi mono. Discontinuation rates were high for pts receiving BTKis (62%; 279/449) and Bcl-2is (61%; 67/109). Among BTKi discontinuers, toxicity (54%; 150/279) was the most common reason for discontinuation, followed by disease progression (12%; 34/279) (Figure 1B). Among Bcl-2i discontinuers, toxicity (36%; 24/67) was the most common reason for discontinuation, followed by completion of regimen (30%; 20/67) (Figure 1C). Median duration of treatment was 777 days (95% CI: 632-920) for the BTKis group and 639 days (95% CI: 335-755) for the Bcl-2is group. Median treatment duration in days was comparable between mono and combination regimens in both BTKis (782 vs. 809) and Bcl-2is (747 vs. 718) groups.Conclusions:RWD show standard of care shifted from chemoimmunotherapy to targeted therapies. Pts receiving targeted therapies had high rates of discontinuation, most commonly due to toxicity. Most targeted regimens were mono; more BTKi pts were treatment naive compared to Bcl-2i pts. Slow adoption of fixed-duration therapy with the Bcl-2i combination regimen was observed. The duration of Bcl-2i mono was comparable to that of the Bcl-2i combination regimens, and a high number of pts initiating combo regimens continued on mono regimens in contrast to regimens studied in randomized controlled trials. [Display omitted] DisclosuresSmith: Novartis: Current Employment; Pfizer: Ended employment in the past 24 months. Owusu: Novartis: Current Employment; Roche: Ended employment in the past 24 months. Wormser: Roche: Current equity holder in publicly-traded company; Novartis: Current Employment, Current equity holder in publicly-traded company. Woo: Novartis: Current Employment, Current equity holder in publicly-traded company.

Outcomes of Chronic Lymphocytic Leukemia and Richter Transformation Following Discontinuation of Non-Covalent Bruton's Tyrosine Kinase Inhibitors

Outcomes of Chronic Lymphocytic Leukemia and Richter Transformation Following Discontinuation of Non-Covalent Bruton's Tyrosine Kinase Inhibitors