Low Discontinuation Rate Research Articles

Safety, efficacy, and outcomes of 90-yttrium radioembolization in combination with immune checkpoint inhibitors as a definitive first-line treatment approach in non-surgical hepatocellular carcinoma.

617 Background: Immune checkpoint inhibitors (ICI) have emerged as first line therapy for advanced-stage hepatocellular carcinoma (HCC). However, response rates remain modest (<20%). Combination treatments offer potential to improve initial response rates while extending duration of response. While early studies of 90 Yttrium transarterial radioembolization ( 90 Y)-ICI showed fewer adverse events (AE) and improved objective responses (OR) (30-40%), there were no improvements in time to progression (TTP) and overall survival (OS). This study evaluates safety, efficacy, and outcomes of first line 90 Y-ICI while evaluating the role of ICI regimen and treatment sequencing. Methods: A retrospective, multi-center study was conducted in BCLC A-C stage HCC patients (ECOG 0-1) receiving first line 90 Y-ICI with atezolizumab/bevacizumab (A+B) or tremelimumab/durvalumab (STRIDE). Treatment response was recorded at 90 Y follow-up. TTP, progression-free survival (PFS), and OS were primary endpoints, with AE and safety as secondary outcomes. Results: The study included 40 patients receiving 90 Y-ICI from 2021–2024, with a median follow-up of 12 months. The cohort was predominantly Child-Pugh A (96%) with HCV-related cirrhosis (76%), BCLC-C stage (51%), and a median target HCC size of 7.7 cm (IQR, 6-11 cm). Grade 3-4 AEs occurred in 15 patients (37%), leading to steroid use (12, 29%), treatment delays (13, 31%), or discontinuation (4, 10%). The first cycle target OR rate was 82% (32/39), with a 51% (20/39) complete response (CR) rate. The first cycle overall OR was 59% (23/39), with a 41% (16/39) CR rate. No significant differences were found in adverse events, delays, or discontinuations based on sequencing or regimen. Sequencing had no significant effect on target or overall OR with no downstream effect on TTP (P = 0.968) or PFS (P = 0.906). Similarly, there was no effect of ICI regimen on OR, TTP (P = 0.813) or PFS (P = 0.904), although the data trended toward higher response rates with the STRIDE regimen. Log-rank analysis revealed target CR was associated with improved TTP (P = 0.004) and PFS (P = 0.009), but not OS (P = 0.237). Achieving an overall CR was associated with further improvements in TTP (P < 0.001) and PFS (P < 0.001). The cohort 2-year OS was 55% with median OS not yet reached. Conclusions: First line 90 Y-ICI therapy in BCLC A-C stage HCC is an effective treatment strategy with AEs in the expected range of systemic therapy and low rates of treatment discontinuation. Sequencing and ICI regimen did not significantly impact AEs or treatment outcomes. However, patients achieving CR showed significantly improved TTP and PFS. Although follow-up is limited, these findings suggest achieving CR is key to optimal long-term outcomes. We anticipate long-term follow-up will demonstrate an OS benefit linked to first line CR rate.

New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor-Positive Breast Cancer.

Oral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists that have the potential to overcome common resistance mechanisms to endocrine therapy in estrogen receptor-positive breast cancer. There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.

P0720 Cost-effectiveness of vedolizumab vs. ustekinumab as first-line biologic in treatment sequencing for ulcerative colitis in Canada

Abstract Background Vedolizumab and ustekinumab are biologic therapies indicated for adult patients with moderately to severely active ulcerative colitis (UC). Multiple factors can determine the choice of first-line biologic including response/remission rate, discontinuation rates, safety profile and treatment costs. An economic evaluation can be used to synthesize evidence to identify the optimal treatment sequences to maximize clinical and economic outcomes. The objective was to evaluate the cost-effectiveness of vedolizumab followed by ustekinumab vs. ustekinumab followed by vedolizumab for adult patients with UC who are anti-tumor necrosis factor (TNF)-naïve from a societal perspective in Canada. Methods A Markov model estimated the cost-effectiveness of two sequences for adult patients with UC who are anti-TNF-naïve: vedolizumab as first-line biologic followed by ustekinumab vs. first-line ustekinumab followed by vedolizumab. For both sequences, patients were assumed to receive adalimumab, infliximab, or tofacitinib as a third-line option with surgery available after failing the third-line treatment. Treatment effectiveness (response, remission, discontinuation, and safety profile) was informed by a de novo network meta-analysis.1 Since effectiveness data by treatment line were unavailable, treatment effectiveness was assumed to diminish by 10% for all subsequent therapy lines based on expert opinion.2,3 Treatment costs were informed by IQVIA DeltaPA List Prices, Ontario Drug Benefit Formulary, and recent Canada’s Drug Agency health technology assessments (HTAs). A clinical expert was consulted to ensure alignment with real-world practices. Utilities were informed by published literature and previous HTAs. A lifetime time horizon was taken, with costs and outcomes discounted at 1.5%. Probabilistic base-case analyses (n = 3,000) reported total costs (2024 Canadian dollars) and quality-adjusted life-years (QALYs). Scenario analyses explored the impact of different assumptions. Results The vedolizumab-first sequence resulted in an incremental gain of 0.013 QALYs (12.791 vs. 12.778) and saved $157 ($291,529 vs. $291,686). Patients remained on first-line biologic longer with the vedolizumab-first sequence due to a lower discontinuation rate. The vedolizumab-first sequence remains dominant if treatment effectiveness at later lines is assumed consistent with first-line, from a payer perspective and varying time horizons. Conclusion From this model, a vedolizumab-first treatment sequence was dominant resulting in incremental clinical benefit, and cost savings from a societal perspective, suggesting that this treatment strategy provides better value for anti-TNF-naïve patients with moderate-to-severe UC in Canada.

Real-World Effectiveness and Tolerability of Dolutegravir and Lamivudine 2-Drug Regimen in People Living with HIV: Systematic Literature Review and Meta-Analysis.

Dolutegravir (DTG) + lamivudine (3TC) demonstrated high rates of virologic suppression (VS) and low rates of virologic failure (VF), discontinuation, and drug resistance in randomized trials. Real-world evidence can support treatment effectiveness, safety, and tolerability in clinical practice and aid in treatment decisions. A systematic literature review (SLR) was conducted to identify studies using DTG + 3TC (January 2013-March 2024). Studies were screened to include observational studies reporting 48- or 96-week on-treatment VS, VF, or discontinuation outcomes; proportions of individuals with each outcome at each time point were estimated using random- and common-effects models. Of 249 SLR-identified publications, 43 reported consistently defined outcomes of interest at comparable time points, representing 1480 individuals naive to antiretroviral therapy (ART) and 12,234 individuals with prior ART experience. At weeks48 and 96, respectively, estimated proportions (95%CIs; random-effects model) with on-treatment VS were high (naive to ART, 0.964 [0.945-0.979] and 0.902 [0.816-0.966]; prior ART, 0.966 [0.950-0.980] and 0.971 [0.946-0.990]), with low estimated proportions experiencing VF (naive to ART, 0.001 [0.000-0.013] and 0.001 [0.000-0.008]; prior ART, 0.009 [0.005-0.015] and 0.015 [0.007-0.024]) and discontinuations for any reason (naive to ART, 0.052 [0.019-0.097] and 0.130 [0.084-0.183]; prior ART, 0.067 [0.042-0.098] and 0.084 [0.047-0.130]). Across identified studies (> 44,000 unique individuals), those reporting resistance outcomes at VF/blip (regardless of emergence) detected integrase strand transfer inhibitor (INSTI) mutations in 0 of 2346 individuals naive to ART and 0.02% (4/20,060) of individuals with prior ART experience (S147G, R263K, G118R + E138K, T66A + G118R + E138K); additionally, N155H was reported in an individual using DTG + 3TC with unknown baseline ART status. Overall treatment outcomes in real-world settings confirm the efficacy, tolerability, and high barrier to resistance seen in phase3 trials across diverse populations, including those naive to ART or with prior ART experience.

Long-Term clinical efficacy of liraglutide for type 2 diabetes: real-world evidence and outcomes from Pakistan.

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and promoting weight loss in clinical trials. However, real-world data from diverse populations, particularly from South Asia, are limited. The study aims to evaluate the long-term efficacy and safety of liraglutide in a real-world setting among Pakistani patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study of 624 patients initiated on liraglutide was conducted. Data were collected at baseline and 6, 12, 18, and 24 months. Primary outcomes were HbA1c and weight changes. Secondary outcomes included fasting plasma glucose, lipid profile, and blood pressure. Statistical analyses were performed using appropriate methods. In study population the mean HbA1c reduction of -1.45 ± 0.67% was observed at 24 months, with 30.6% achieving HbA1c ≤ 7.5%. A rapid and sustained weight loss of -7.51 kg was achieved, with 27.2% experiencing ≥5% weight loss. Additionally, liraglutide led to a significant reduction in LDL cholesterol, with 46.7% of patients achieving a ≥ 10% reduction at 24 months. Liraglutide was well-tolerated, with a low discontinuation rate of 4.6%. Liraglutide demonstrated sustained efficacy and safety in a diverse Pakistani population with T2DM, regardless of baseline characteristics. These findings support the use of liraglutide as an effective treatment option for T2DM in real-world clinical practice.

Trends in medications for autoimmune disorders during pregnancy and factors for their discontinuation: a population-based study

ObjectivesThe medications used for autoimmune diseases have significantly evolved in recent years, but there is limited knowledge about how treatment practices changed during pregnancy. This study aimed to describe the temporal trends of immunosuppressants, immunomodulators and biologics use during pregnancy among women with autoimmune diseases, compare their use before, during, and after pregnancy, and identify factors predicting the discontinuation of these medications during pregnancy.MethodsUsing data from the Quebec Pregnancy Cohort (1998–2015), which included women under the RAMQ prescription drug plan for at least 12 months before and after pregnancy, the analysis focused on those with at least one International Classification of Diseases Ninth or Tenth Revision code in the year before pregnancy for inflammatory bowel disease, rheumatoid arthritis, spondylarthropathies, connective tissue diseases, systemic lupus erythematosus, or vasculitis. Exposure to immunosuppressants, immunomodulators and biologics were evaluated before and during the pregnancy. Discontinuation during pregnancy was defined as having no prescriptions filled during pregnancy or overlapping with the first day of gestation (1DG), given that at least one prescription was filled in the year prior to pregnancy. Generalized estimating equations were applied to estimate adjusted odds ratios (aOR) for predicting medication discontinuation during pregnancy.ResultsAmong 441,570 pregnant women, 3,285 had autoimmune diseases. From 1998 to 2014, the use of immunomodulators increased from 3.7% to 11.9%, immunosuppressants from 4.1% to 13.7%, and biologics from 0% to 15.6%. During pregnancy, compared to before, there was a significant decrease in exposure to immunomodulators (8.6% to 5.4%), immunosuppressants (14.2% to 8.7%), and biologics (5.1% to 4.7%). Factors influencing discontinuation varied by medication type; for immunosuppressants, prior biologics use (aOR = 2.12, 95%CI 1.16–3.85) and the year of pregnancy (aOR = 0.93, 95%CI 0.89–0.98) were key factors, while for biologics, it was only the year of pregnancy (aOR = 0.68, 95%CI 0.54–0.86).ConclusionsThe use of immunomodulators, immunosuppressants, and biologics has increased over time. However, exposure during pregnancy decreased, with recent years showing a lower rate of discontinuation. Understanding the factors influencing medication discontinuation during pregnancy can improve management strategies for women with autoimmune diseases.

Drug Survival, Retention, and Persistence of Dupilumab in Adults and Adolescents with Atopic Dermatitis: A Narrative Literature Review.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that can have a negative impact on a patient's quality of life. Long-term effectiveness is required to manage the symptoms of AD (skin inflammation, eczematous lesions, and itching). Because some of the systemic immunosuppressants used to treat AD have been associated with serious adverse events (AEs), other safer, more effective options, including dupilumab, have been proven effective long-term for treatment of adult and adolescent patients with moderate-to-severe AD. The long-term safety and effectiveness of a drug are usually confirmed in real-world studies by evaluating its performance over time. Measures such as drug survival, drug retention, drug persistence, or retention rates reflect whether treatment may be considered as satisfactory by both patients and physicians, meeting key clinical needs. This review aimed to describe the survival, retention, or persistence of dupilumab therapy in adults and adolescents with moderate-to-severe AD by conducting a PubMed search in March 2023 and screening for relevant publications. Globally, real-world studies with dupilumab have regularly reported high drug survival rates after 1, 2, and 3years of observation, being consistently at 80-90%, with low rates of treatment discontinuation due to lack of efficacy or AEs. These findings are notably higher than 1- and 2-year drug survival rates of systemic immunosuppressants (including cyclosporine [37% and 20%, respectively] and methotrexate [41% and 33%, respectively]). Overall, real-world data on drug survival have confirmed that dupilumab provides long-term sustained efficacy and acceptable safety in patients with moderate-to-severe AD.

Cost-effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: the brazilian case with bayesian networks and markov influence diagrams

Abstract Background Heart failure (HF) is one of the leading causes of death worldwide, with a significant burden in middle-income countries, such as Brazil. Mineralocorticoid receptor antagonists (MRAs) have been established as a cornerstone in the treatment of HF with reduced ejection fraction (HFrEF), but their adoption has faced obstacles. Until recently, spironolactone was the only MRA available in Brazil, with restricted use due to associated side effects, such as gynecomastia and hyperkalemia. However, the introduction of new MRAs, such as finerenone and eplerenone, has the potential to change the therapeutic landscape. Understanding the cost-effectiveness of these agents in the Brazilian healthcare context is essential to optimize HF management. Methods A Bayesian Network approach complemented by Markov Influence Diagrams was employed to estimate incremental cost-effectiveness ratios (ICERs), presented in international dollars (Int$) gained per quality-adjusted life year (QALYs). Discontinuation rates for MRAs were incorporated into the model, reflecting real-world clinical practice, along with a 5% annual discount rate for both costs and effectiveness. To inform our model, a comprehensive systematic review was conducted, followed by a network meta-analysis (NMA) to assess the comparative effectiveness of ARMs. Data on incident cardiovascular outcomes were derived from a Brazilian real-world cohort of 1,098 patients with HFrEF. All cost assessments were made from the perspective of the Brazilian public health system, with values converted to Int$. Results The NMA highlighted that spironolactone [HR:0.75 (95%CI 0.67-0.84)], eplerenone [HR:0.84 (95%CI 0.77-0.93)] and finerenone [HR:0.90 (95%CI 0.82-0.98)] significantly reduced the relative risk of all-cause mortality compared to no MRA utilization. Notably, eplerenone significantly reduced hospitalizations due to HF [HR:0.60 (95%CI 0.41-0.90)] compared to no MRA therapy, with spironolactone and finerenone showing HRs of 0.68 (95%CI 0.40-1.17) and 0.83 (95%CI 0.59-1.15) . The analysis also revealed a notably higher risk of MRA discontinuation for finerenone (22%) and spironolactone (51%) compared to eplerenone. In cost-effectiveness comparisons, finerenone was dominated by alternatives, while eplerenone exhibited an ICER of Int$2,614 (95%CI 1,851-3,470)/QALY when compared to spironolactone. Both spironolactone and eplerenone emerged as cost-effective options when compared to no MRA therapy, with eplerenone being particularly favorable below the willingness-to-pay threshold of Int$8,900 per QALY. Conclusions In the Brazilian healthcare context, eplerenone will likely be the most cost-effective MRA compared to spironolactone, offering both a reduction in HF-related hospitalizations and a lower discontinuation rate. These findings underscore the value of integrating cost-effectiveness analyzes into healthcare decision-making processes.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids

ObjectivesTo compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. MethodsWe retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. ResultsA total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. ConclusionsLower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

Transthyretin amyloid cardiomyopathy: Literature review and red-flag symptom clusters for each cardiology specialty.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is a progressive and infiltrative cardiac disorder that may cause fatal consequences if left untreated. The estimated survival time from diagnosis is approximately 3-6years. Because of the non-specificity of initial symptom manifestation and insufficient awareness among treating physicians, approximately one-third of patients with ATTRwt-CM are initially misdiagnosed with other cardiac diseases. Although heart failure (HF) is the most common initial manifestation of ATTRwt-CM, observed in nearly 70% of affected patients, patients may also present with other cardiologic symptoms, such as atrial fibrillation (AF) and aortic stenosis (AS). This non-specific and diverse nature of the initial ATTRwt-CM presentation indicates that various cardiology subspecialties are involved in patient diagnosis and management. Standard guideline-directed pharmacological treatment for HF is not recommended for patients with ATTRwt-CM because of its limited effectiveness. However, no established algorithms are available regarding HF management in this patient population. This literature review provides an overview of the red flags for ATTRwt-CM and research findings regarding HF management in this patient population. In addition to commonly recognized red flags for ATTRwt-CM (e.g., HF, AF and severe AS), published literature identified potential red flags such as coronary microvascular dysfunction. For HF management in patients with ATTRwt-CM, the use of mineralocorticoid receptor antagonists (MRAs) was reported as a well-tolerated option associated with a low discontinuation rate and reduced mortality. Although there is no concrete evidence for recommendations against sodium-glucose cotransporter 2 inhibitor (SGLT2i) administration, research supporting its use is limited to small-scale studies. Robust evidence is lacking for AF ablation, implantable cardioverter-defibrillators and cardiac resynchronization therapy. Based on the published findings and our clinical experience as Japanese ATTRwt-CM experts, red-flag symptom clusters for each cardiology specialty (HF, arrhythmia and ischaemia/structural heart disease) and a treatment scheme for HF management are presented. As this research area remains at an exploratory stage, our observations would require further discussion among experts worldwide.

Asciminib monotherapy as frontline treatment of chronic-phase chronic myeloid leukemia: results from the ASCEND study

AbstractAsciminib is a myristoyl site BCR::ABL1 inhibitor approved for patients with chronic-phase chronic myeloid leukemia (CP-CML) failing ≥2 prior lines of therapy. The Australasian Leukaemia and Lymphoma Group conducted the Asciminib Evaluation in Newly Diagnosed CML study to assess efficacy of asciminib for newly diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily. Patients with treatment failure, defined as BCR::ABL1 of >10% at 3 or 6 months, or >1% at 12 or 18 months, received either imatinib, nilotinib, or dasatinib in addition to asciminib. In patients with suboptimal response, defined as levels of 1% to 10% at 6 months, >0.1% to 1% at 12 months, or >0.01% to 1% at 18 months, the asciminib dose was increased to 80 mg twice daily. With a median follow-up of 21 months (range, 0-36), 82 of 101 patients continue asciminib. Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%). There were no deaths; 1 patient developed lymphoid blast crisis. The coprimary end points were early molecular response (BCR::ABL1 of ≤10% at 3 months), achieved in 93% (96% confidence interval [CI], 86-97%), and major molecular response by 12 months achieved in 79%; (95% CI, 70-87%), respectively. Cumulative incidence of molecular response 4.5 was 53% by 24 months. One patient had 2 cerebrovascular events; no other arterial occlusive events were reported. Asciminib as frontline CP-CML therapy leads to high rates of molecular response with excellent tolerance and a low rate of discontinuation for toxicity. This trial was registered at https://www.anzctr.org.au/ as #ACTRN12620000851965.

Angiotensin Receptor Blockers Versus Angiotensin Converting Enzyme Inhibitors in Acute Myocardial Infarction Without Heart Failure

BackgroundWhether angiotensin II receptor blockers (ARBs) can be an alternative to angiotensin-converting enzyme inhibitors (ACEIs) in patients without heart failure (HF) after acute myocardial infarction (MI) remains controversial. The aim of this study was to compare clinical outcomes between initial ARB and ACEI therapy in patients with MI without HF. MethodsBetween 2010 and 2016, a total of 31,013 patients who underwent coronary revascularization for MI with prescription of ARBs or ACEIs at hospital discharge were enrolled from the Korean nationwide medical insurance data. Patients who had HF at index MI were excluded. The primary outcome was all-cause death. The secondary outcomes included recurrent MI, hospitalization for new heart HF, stroke, and a composite of each outcome. ResultsOf 31,013 patients, ARBs were prescribed in 12,685 (40.9%) and ACEIs in 18,328 (59.1%). Patients receiving ARBs had a lower discontinuation rate compared with those receiving ACEIs (28.2% vs 43.5%, adjusted hazard ratio [HR] 0.34; 95% confidence interval [CI] 0.31-0.37; P < .01). During a median follow-up of 2.2 years, 2480 patients died. The incidence rate of all-cause death in patients receiving ARBs and those receiving ACEIs was 27.7 and 22.9 per 1000 person-years, respectively (adjusted HR 1.04; 95% CI 0.95-1.13; P = .40). There were no significant differences in the secondary outcomes between patients receiving ARBs and those receiving ACEIs, except stroke (19.2 vs 13.6 per 1000 person-years; adjusted HR 1.17; 95% CI 1.04-1.32; P = .01). In a subgroup analysis, a higher mortality was observed with ARBs compared with ACEIs in patients with diabetes. ConclusionsIn this nationwide cohort, there was no significant difference in the incidence of all-cause death between ARBs and ACEIs as discharge medications in patients with myocardial infarction without heart failure. Angiotensin II receptor blockers would be an alternative to ACEIs for those intolerant to ACEI therapy.

Persistence of advanced systemic pharmacological treatment of moderate-to-severe psoriasis among bio-naïve patients-A retrospective register-based cohort study in Finland and Sweden.

Plaque psoriasis (PsO) requires long-term treatment for symptom control and remission; thus, a long-term pharmacological intervention is necessary. Treatment persistence reflects long-term therapeutic effectiveness and tolerance. This study investigates drug persistence and compares treatment discontinuation rates across biologic agents and apremilast used by PsO patients in Finland and Sweden. This retrospective register-based cohort study included bio-naïve patients (≥18 years) with moderate-to-severe PsO, who initiated treatment with abatacept, adalimumab, brodalumab, certolizumab pegol, etanercept, golimumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, ustekinumab or apremilast during 2008-2020 in Finland or Sweden. The main analysis evaluated persistence (based on duration of continuous treatment) and compared rates of treatment discontinuation using guselkumab as reference drug, during 2018-2020 in Finland. Treatment discontinuation was assessed by survival analysis of the time to first drug discontinuation, including switching to other study drugs. Due to limited sample size (n < 20), certain biologics (abatacept, brodalumab, certolizumab pegol, etanercept, golimumab, risankizumab and tildrakizumab) were excluded from the persistence analysis. In Finland, 709 patients fulfilled the inclusion criteria during 2018-2020 for the main analysis. The highest persistence was observed for guselkumab and ustekinumab with 90 and 85% of treated patients, respectively, continuing treatment for ≥1 year. Comparable results were observed in the expanded cohort analysis (index starting in 2008; 2745 bio-naïve patients in Finland and 10,970 in Sweden). Furthermore, patients treated with guselkumab in Finland showed lower treatment discontinuation rates compared to other study drugs. Guselkumab and ustekinumab demonstrated high persistence as measured by continued treatment for at least 1 year. Furthermore, these treatments demonstrated lower rates of discontinuation compared to other study drugs included in the analysis. Understanding the balance between efficacy and feasibility in treatment decisions is crucial, as feasibility may impact persistency outcomes and potentially increase persistency rates.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation

Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg versus other long-acting reversible contraceptives for contraception in Spain

Introduction Condoms and combined oral contraceptive pills are widely used in Spain with high failure rates. Long-Acting Reversible Contraceptive (LARC) methods offer better efficacy and adherence and reduce unintended pregnancies (UP) compared with short-acting reversible contraceptive (SARC) methods. Objective To assess the cost-effectiveness of LNG-IUS 52 mg (Mirena®) versus other LARC for contraception in Spain. Materials and Methods A Markov model with annual cycles and an eight-year time horizon was developed from the Spanish national healthcare system (NHS) perspective, considering costs for contraceptive method acquisition, health care resources (HCR) and UP. Effectiveness was based on failure and discontinuation rates. Sensitivity analyses were performed to test the model’s robustness. Results LNG-IUS 52 mg (Mirena®) resulted in lower costs and fewer UP versus LNG-IUS 13.5 mg (Jaydess®), Implant (Implanon®) and Copper IUD. LNG-IUS 52 mg (Levosert®) prevented the same UP events at a higher cost. LNG-IUS 19.5 mg (Kyleena®) was the most effective option, due to a lower discontinuation rate. Conclusions LNG-IUS 52 mg (Mirena®) is the least costly LARC, driven by lower acquisition costs and reduced HCR utilisation. Increasing LNG-IUS 52 mg (Mirena®) uptake in contraception could generate further cost savings for the Spanish NHS and reduce economic burden of UP.

Clinical Course of Bio Naive Ulcerative Colitis Patients Five Years After Initiation of Adalimumab in a Nationwide Cohort.

There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug. We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up. A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14-2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48-1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission. Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.

Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment. Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs). Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy. Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

Factors that impact aromatase inhibitor adherence in early-stage hormone receptor positive breast cancer.

e12524 Background: Despite efficacy of aromatase inhibitors (AI) in improving survival for patients with hormone receptor positive (HR+) breast cancer, adherence to AI remains suboptimal. The aim of this study is to evaluate factors that may affect patient adherence to first-line AI. Methods: We retrospectively reviewed records of 195 female patients with HR+, HER2 negative early-stage breast cancer who were started on first-line adjuvant AI between 2011-2020 at our academic institution. We collected information on recurrence risk (defined by Oncotype score, with low risk ≤ 15, moderate risk 16-25, high risk ≥ 26), AI-related side effects, supportive therapy use for side effects, and socioeconomic demographics (i.e. income, insurance type, and race). We linked median family income with zip codes based on national census data and sorted them based on the Pew Research Center categorization. The primary end point was the rate of first-line AI adherence at 4 years. The Kruskal-Wallis rank sum test, Fisher’s exact test, and Pearson’s chi-squared test were used to compare AI adherence when varying patient profiles. Results: In our cohort, 50% (n=98) were adherent to first-line AI at 4 years, 9% (n=17) were still taking first-line AI but have not yet reached 4 years, and 41% (n=80) discontinued first-line AI early. Of those who discontinued first-line AI early, 68% (n=54) switched to an alternate endocrine treatment due to side effects, 4% (n=3) stopped all endocrine treatment, and 28% (n=23) were lost to follow up. AI-related side effects were common; 83% (n=162) reported AI-related side effects, yet only 27% of those patients received supportive therapy. Supportive therapy use was not significantly different when varying patients’ recurrence risk and socioeconomic demographics. In addition, adherence did not differ based on side effect frequency or supportive therapy use. The population’s Oncotypes included 36% (n=70) low risk, 36% (n=70) moderate risk and 12% (n=24) high risk; the remaining had no Oncotype sent. There was no significant difference in adherence among the risk groups. In evaluating demographics, the cohort’s median age was 62 and it included 9% Asian, 13% Black, 5% Hispanic, 54% White, and 19% Other/Unknown. The majority (62%) of patients were of middle income ($52,000-145,000), followed by 29% in upper and 9% in lower income. The minority (22%) of patients were on Medicaid. Those with a lower discontinuation rate were older (64 vs. 61, p=0.019), while there was no significant difference based on race, income, or insurance. Conclusions: Despite the small sample, it is reassuring that at our institution, long term adherence to first-line AI and supportive therapy use did not vary among socioeconomic demographics. However, a gap persists between the prevalence of AI-related side effects and usage of proven supportive treatments. Further study on strategies to enhance AI tolerance and adherence is needed.

Treatment discontinuation due to toxicity for patients with acute myeloid leukemia (AML) treated on SWOG S1203.

6529 Background: Curative-intent therapy for patients with newly diagnosed AML centers on the use of cytarabine as part of an intensive multi-drug induction regimen. Treatment-related toxicity may lead to patients stopping treatment, despite the considerable risk of inadequately treated AML. We compared rates of protocol therapy discontinuation due to adverse events (AEs) in either of two standard induction regimens (7+3 or high dose cytarabine + idarubicin, IA) on the S1203 study (Garcia-Manero; Leukemia 2023). Methods: S1203 was a randomized study of patients &lt;60 years old with newly diagnosed AML. Patients were required to have performance status (PS) &lt;3, ejection fraction &gt;45%, and no prolonged QTc interval or known cardiac disease. There were no exclusion criteria for kidney or liver function. On the 7+3 induction arm, subjects received daunorubicin 90 mg/m2 IV daily days 1-3 with continuous infusion cytarabine 100 mg/m2 daily days 1-7. On the IA arm, subjects received idarubicin 12 mg/m2 daily days 1-3 with continuous infusion cytarabine 1.5 g/m2 daily days 1-4. Toxicities were assessed per the Common Terminology Criteria for Adverse Events version 4.0. Rates of discontinuation were compared using Fisher’s exact test. Results: From 4/2013-11/2015, 522 subjects were randomized (261 to each arm). Treatment discontinuation due to either death or toxicity occurred in 8 vs 22 patients on 7+3 vs IA respectively (p=0.014). During induction, 0 patients on the 7+3 arm discontinued treatment due to toxicity versus 4 patients on the IA arm (0% vs 2%; p=0.12). Toxicities leading to treatment discontinuation on the IA arm included congestive heart failure (n=2, one with concurrent arrhythmia), acute kidney injury (n=1), and hypotension complicated by stroke and cardiac arrest (n=1). Two of the 4 patients who discontinued treatment due to toxicity on IA achieved a complete remission after their first cycle. For patients with PS 2-3 (n=40 on 7+3, n=27 on IA), rates of grade 3-5 AEs were 85% vs 86% and rates of grade 5 AEs were 0% vs 11% (p=0.065). Conclusions: 7+3 was well tolerated. Excluding patients from S1203 with PS 2-3 or decreased hepatic/renal function would not have prevented treatment-related toxicity. The low rate of protocol therapy discontinuation due to toxicity suggests that eligibility criteria for clinical trials could be further broadened to improve patient access. Clinical trial information: NCT0180233 . [Table: see text]