Drug Discontinuation Rates Research Articles

One-Month Outcomes of Cases Receiving Ticagrelor after Percutaneous Coronary Intervention; a Case Series.

Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist that can block ADP-induced platelet aggregation. This study aimed to describe one-month follow-up findings of cases undergoing ticagrelor therapy after percutaneous coronary intervention (PCI). This case series was performed on acute coronary syndrome (ACS) patients who were candidates for PCI and received aspirin plus ticagrelor after PCI. Patients were followed for one month and their outcomes were described. 156 cases with the mean age of 59.74 ± 9.24 years were studied (63% male). 45 (28.8%) cases complained of dyspnea (39 cases with mild and 6 cases with severe dyspnea). Bleeding occurred in 4 (2.5%) cases (intra-cranial hemorrhage (ICH) in one, hematuria in two, and skin hemorrhage in one case). There were no cases with bradycardia or thrombosis. One (0.6%) patient developed drug hypersensitivity reaction, which manifested as skin rash. The use of drug was stopped in 10 (6.4%) cases due to severe dyspnea (n= 6), ICH (n=1), skin rash (n=1), and concomitant left ventricular (LV) clot (n=2). The most important finding of one-month ticagrelor consumption were dyspnea, bleeding, and hypersensitivity reaction. No case of bradycardia and stent thrombosis was detected. In our study , iranian population has more susceptibility to dyspnea than PLATO result. The rate of drug discontinuation in this series of cases was 6.4 %.

Drug survival, discontinuation rates, and safety profile of secukinumab in real-world patients: a 152-week, multicenter, retrospective study.

Psoriasis is a chronic systemic disease that requires long-term management. Despite data on follow-up studies going back 5years, little is known about the condition's sustainability based on patient profiles. The aim of this study was to analyze drug survival and discontinuation rates for secukinumab treatment under real-world conditions. Patients with moderate-to-severe plaque psoriasis treated in the dermatology department of five Spanish medical centers between 2015 and 2019 were included in our retrospective study. Drug survival was assessed with Kaplan-Meier analysis plots and multivariate regression. In total, 171 treated patients were retrospectively recorded and analyzed for 152weeks (37.40% had been diagnosed with psoriatic arthritis [PsA]). The discontinuation rate in the PsA group was 14.10% vs. 12.10% among those who had no PsA. The mean survival time of discontinuation was 63weeks for PsA vs. 65weeks for no PsA (P=0.913). Secukinumab's estimated mean survival in PsA patients was 86% (estimated mean survival time 130weeks) vs. 88% (estimated mean survival time of 133weeks) in non-PsA patients (P=0.676). The mean survival time of patients in secukinumab treatment was comparable in all patient profiles and better than the data found in clinical trials and real-life studies.

Angiotensin receptor neprilysin inhibitor in heart failure with reduced ejection fraction: Real-world experience from a safety perspective

Background: Angiotensin receptor neprilysin inhibitor (ARNI) reduces morbidity and mortality in patients of heart failure with reduced ejection fraction (HFrEF). However, the use of ARNI in real-world practice is limited by safety issues, especially in acute decompensated heart failure (ADHF) patients. Methods and Results: Forty-seven hospitalized ADHF inpatients and 53 chronic compensated heart failure (CCHF) outpatients were enrolled in the study. ARNI was initiated and aimed to be up-titrated to a target dose of 97 mg of sacubitril with 103 mg of valsartan twice daily. Efficacy endpoints were New York Heart Association functional class, 6-min walk distance (6MWD), change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels and left ventricular ejection fraction (LVEF) from baseline with follow-up at 1 month, 6 months, and 2 years. Safety endpoints were the rates of worsening serum creatinine, hyperkalemia, symptomatic hypotension, angioedema, and need for drug discontinuation. Cumulative adverse drug effect was observed in 42.6% and 13.2% patients of ADHF and CCHF groups, respectively. The most common side-effect was symptomatic hypotension that occurred in 10 (21.3%) patients of ADHF group and 3 (5.7%) patients of CCHF group. Drug discontinuation rate was 19.1% in ADHF group and 3.8% in CCHF group. Significant improvement was seen in both the groups with respect to 6 MWD, functional class, change in NT-pro BNP levels and LVEF. At 2-year follow-up, 3 (6.4%) deaths occurred in ADHF group while none was reported from CCHF group. Conclusion: ARNI results in a significant clinical, biochemical, and functional improvement in HFrEF patients but at the cost of worsening renal function and hypotension especially in ADHF setting.

Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group

BackgroundWe evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi).Patients and methodsWe conducted a prospective–retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs.ResultsFrom July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3–4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0–not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events.ConclusionsTreatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs.Trial registration numberNCT04133207

Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial

BackgroundVariation in patient characteristics and practice patterns may influence outcomes at a regional level. MethodsWe assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding. ResultsCompared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking ≥9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0–3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with warfarin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03). ConclusionsPatients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific.

Low Rate of Drug Discontinuation, Frequent Need for Dose Adjustment, and No Association with Development of New Arthralgia in Patients Treated with Vedolizumab: Results from a Tertiary Referral IBD Center.

Evaluating clinical data on the safety and efficacy of vedolizumab (VDZ) in 'real-world' setting is still desirable. Recent reports have raised concerns that arthralgia may be associated with VDZ. The aim of this study is to present clinical experience with VDZ from a tertiary IBD center. Retrospective chart reviews were performed of consecutive patients exposed to VDZ between 2015 and 2018. Clinical, biomarker, and endoscopic efficacy and safety data were evaluated. A total of 130 IBD (75CD, 55UC) patients were included. Median duration of VDZ therapy was 65weeks. Probability of drug discontinuation was 4.9% and 9.4% at 1 and 2 years. Dose intensification was more frequent in CD compared to UC (at 1 and 2years: 64.8/87.9% vs. 26.5/35.7%, p < 0.001). Clinical remission rates at 3-, 6- and 12months were 44.4%, 71.4% and 77.1% in UC, and 9.1%, 26.7% and 29.2% in CD patients, respectively. Prior use of multiple biologic agents was associated with diminished efficacy of VDZ in CD. Three new cases of arthralgia were encountered during follow-up. Vedolizumab (VDZ) therapy displayed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure. Frequent dose intensification was required. The safety profile was good, and no association between newly onset arthralgia and VDZ therapy was observed.

SGLT2 Inhibitors for Treatment of Diabetic Nephropathy

Background: Sodium-glucose co-transporter 2 (SGLT2) are medications approved for treatment of type 2 diabetes. Recent evidence suggests that these agents exert Reno protective effects. Methods: Review of literature (English, French, Spanish) from January 1990 to November 10, 2019. Searching terms include sodium-glucose co-transporters 2 inhibitors (SGLT2) inhibitors, chronic kidney disease (CKD), end-stage kidney disease (ESKD). Randomized trials, meta-analysis, expert opinions and guidelines are also reviewed. Results: The effects of canagliflozin on renal events were evaluated in patients with type 2 diabetes and albuminuric diabetic nephropathy already on renin-angiotensin (RAS) blockade. The primary outcome was a composite of the incidence of ESKD, doubling of serum creatinine, renal or cardiovascular (CV) death. Canagliflozin was associated with 30% reduction in the incidence of this primary outcome [hazard ratio (HR) 0.70, 95% CI 0.59-0.82, P=0.00001)]. Similar results were generally reported in large CV trials of canagliflozin, empagliflozin and dapagliflozin although renal events were secondary or post-hoc outcomes. Renoprotection by SGLT2 inhibitors was observed in patients with different degrees of renal function at baseline, with or without albuminuria, and taking or not RAS blockers. SGLT2 inhibitors were generally safe with drug discontinuation rates similar to placebo. Canagliflozin was tolerated in patients with eGFR &lt;60 ml/min/1.73 m2. The incidence of acute renal injury was numerically less frequent with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors slow progression of diabetic nephropathy and should be standard of care on top of RAS blockers for renal protection in patients with type 2 diabetes. Regulatory authorities should consider allowing using canagliflozin 100 mg/d in patients with estimated glomerular filtration rate (eGFR) between 30-45 ml/min/1.73 m2./p&gt;

Non-Hematologic Therapy Toxicities Correlated with Survival, Drug Discontinuation and Response in Multiple Myeloma Patients: A Retrospective Study

Background The age distribution character makes Multiple myeloma (MM) a geriatric disease. Several geriatric assessment models have built for the identification of the unfit patients and making individual treatments. However, their prediction value on treatment-related toxicities is limited or lacking. It is time to identify the significance of treatment-related toxicities. Methods A total of 119 patients consecutively diagnosed as active MM with previous untreated between 2010 and 2018 in Nanfang Hospital were reviewed. Results Among all 119 patients analyzed, 30 patients exhibited grad 3-4 non-hematologic adverse events (non-HAEs). The MM patients with non-HAEs showed more likely to present geriatric features, such as poor physical status (PS) and renal function, lower hemoglobin (HGB) and albumin (Alb), higher N-terminal B-type natriuretic peptide (NT-proBNP) (P&lt;0.01). Patients with non-HAEs presented poor overall survival (OS), higher drugs discontinuation rate and poor overall response rate (ORR) at 4 months (P&lt;0.01). The multivariate analysis showed that non-HAEs is an independent unfavorable factor for OS, drug discontinuation and response at 4 months. Conclusions Non-hematologic therapy toxicities are correlated with geriatric features, poor survival, high drug discontinuation rate and poor response at 4 months. Disclosures No relevant conflicts of interest to declare.

Comparison of Biologic Discontinuation in Patients With Elderly-Onset Versus Younger-Onset Rheumatoid Arthritis.

ObjectiveThe objective of this study is to compare biologic drug discontinuation rates for older‐ versus younger‐onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices.MethodsWe performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult‐onset rheumatoid arthritis (RA) in 1999‐2013 among residents of a geographically defined area, with follow‐up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death.ResultsA total of 240 cases of elderly‐onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%‐77%) and 53% at 2 years (95% CI: 33%‐66%) for EORA, compared with 61% at 1 year (95% CI: 50%‐69%) and 45% at 2 years (95% CI: 34%‐53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08‐0.53) but not in YORA (interaction P = 0.04).ConclusionDrug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Erratum to: Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1)Trial.

BACKGROUND Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION NCT02559310.

334P - Clinical outcome and toxicity data in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy in a real-world clinical setting

BackgroundClinical trials evaluating treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with aromatase inhibitors (AI) or fulvestrant have shown promising clinical benefit in patients with advanced breast cancer. We evaluated real-world clinical outcomes and toxicity rates in patients with advanced breast cancer who received treatment with CDK4/6i in routine clinical practice. MethodsWe retrospectively reviewed medical records of patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer treated at Departments of Oncology-affiliated with the Hellenic Cooperative Oncology Group (HeCOG). All patients received hormonal therapy in combination with CDK4/6i as first-, second- or third-line of treatment and beyond. The primary end point was progression-free survival (PFS). ResultsFrom 07/2015 to 03/2019, 191 women were treated with CDK4/6i combined with endocrine therapy (median age: 52.2 years, postmenopausal 87, 45.5%); 86 (45%) patients received CDK4/6i in combination with AI and 105 (55%) with fulvestrant. CDK4/6i were administered as first-line treatment in 65 (34%) patients, second-line treatment in 39 (20.4%) and third-line and beyond in 83 (43.5%) patients. The median follow-up was 54.3 months (95%CI 43.0-61.2). The median PFS for patients who received first-line treatment was 18.7 months, second-line treatment 11.5 months and ≥3 lines of treatment 7.5 months. The median overall survival since the initiation of CDK4-6i treatment was 23.2 months (95% CI 20.4-30.3). The most common adverse events were neutropenia (100 patients, 52.4%) and fatigue (24, 12.6%). Grade 3-4 adverse events occurred in 55 (28.8%) patients, while 2 (1.0%) patients permanently discontinued treatment due to toxicity. ConclusionsAmong patients with HR-positive advanced breast cancer treated with CDK4/6i combined with endocrine, the estimated PFS was comparable to previously reported data. Treatment was well tolerated, with a low drug discontinuation rate. Legal entity responsible for the studyHellenic Cooperative Oncology Group. FundingHellenic Cooperative Oncology Group (HeCOG). DisclosureE. Fountzilas: Travel / Accommodation / Expenses: K.A.M ONCOLOGY / HEMATOLOGY; Travel / Accommodation / Expenses: Merck; Shareholder / Stockholder / Stock options: Deciphera. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche Hellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer. G. Fountzilas: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Honoraria (self): AstraZeneca. E. Razis: Honoraria (self), Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genesis Pharmaceuticals; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: , Bristol-Myers Squibb; Travel / Accommodation / Expenses: Genekor. All other authors have declared no conflicts of interest.

Ibrutinib monotherapy outside of clinical trial setting in Waldenström macroglobulinaemia: practice patterns, toxicities and outcomes.

Ibrutinib-related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n=67 (84%), treatment-naïve, n=13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off-study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major-response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2-4] and 5·7 (95% CI: 4-12) months, respectively. The median follow-up was 19 (95% CI: 14-21) months; 18-month progression-free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3-16·7) months, and the median duration-of-response was 32 (range: 23-32) months. Twenty-five patients (31%) had discontinued therapy at last follow-up (68% due to treatment-related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial-fibrillation (11%) were common non-haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.

Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium.

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25IU/mL 12week post-therapy). A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5years, p < 0.0001), had lower body mass indices (22.9kg/m2 vs. 24.6kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes. In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes.ClinicalTrials.govNCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-00146-6) contains supplementary material, which is available to authorized users.

P260 Adverse drug reactions and discontinuation rate during the first year on Orkambi - the earliest results of the STORM study

P260 Adverse drug reactions and discontinuation rate during the first year on Orkambi - the earliest results of the STORM study

Benefits and limitations of TKIs in patients with medullary thyroid cancer: a systematic review and meta-analysis

Introduction Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.

Efficacy and safety profile of roflumilast in a real-world experience.

Roflumilast is the only phosphodiesterase enzyme 4 inhibitor approved in the treatment of chronic obstructive pulmonary disease (COPD) patients with chronic cough and sputum and a history of exacerbations. Real-world studies about the use of roflumilast are limited. Our aim was to assess the efficacy, safety and tolerability of roflumilast in the treatment of stable COPD, in a real-world setting. From August 2014 to August 2017, medical records of all COPD patients who were prescribed roflumilast therapy in Akdeniz University Hospital were analyzed retrospectively. COPD patients were studied in terms of efficacy, safety, and drug discontinuation rate. Efficacy was evaluated as the effect of roflumilast on exacerbation and hospitalization rates of COPD compared to the pre-treatment period. Eighty-three COPD patients treated with roflumilast were included (mean age 66.2±9.3 years, 88.0% male). All the patients were chronic bronchitis and frequent exacerbator clinical phenotype and were classified in the Global Initiative for Chronic Obstructive Lung Disease categories C (n=17; 20.5%) and D (n=66; 79.5%). Mean duration of roflumilast use was 18.9±10.4 months. There was a significant decrease in both COPD exacerbations (2.7 vs. 1.16; P<0.001) and hospitalizations (0.77 vs. 0.32; P<0.001) in roflumilast users compared to the pre-treatment period. Of the patients, 22 (26.5%) experienced adverse events (AE) during their treatment period. The most frequently reported AEs were weight loss (10.8%), loss of appetite (10.8%) and nausea (8.4%). Serious or life-threatening AEs were not detected. Sixteen (19.3%) patients discontinued roflumilast because of AEs. Roflumilast reduced exacerbations and hospitalizations in our real-world population with severe COPD. AEs are common and frequently leading to discontinuation of roflumilast therapy.

Abstract 210: Rates of Drug Switching and Discontinuation among Nonvalvular Atrial Fibrillation Elderly Patients Treated with Direct Oral Anticoagulants in the US

Background: While many studies have demonstrated the efficacy of direct-acting oral anticoagulants (DOACs) for stroke risk reduction among nonvalvular atrial fibrillation (NVAF) patients, there is little information regarding drug switching and discontinuation patterns in real-world settings, particularly in older adults. Thus, we evaluated rates of switching and discontinuation among elderly NVAF patients who initiated any of the three most commonly prescribed DOACs in the US. Methods: Patients ≥65 years who initiated apixaban, rivaroxaban or dabigatran (index event/date) were identified from the Humana database (1/1/2013-9/30/2017) and grouped into cohorts by index DOAC. Patients were required to have an NVAF diagnosis and continuous health plan enrollment for ≥12 months prior to the index date and ≥3 months during the follow-up period after the index date. Percentages of patients in each study cohort who switched to any other DOAC or warfarin or discontinued their index DOAC were evaluated. Multivariable Cox regression analyses were carried out to evaluate the impact of index DOAC treatments on the likelihood of switching or discontinuation while controlling for differences in patient characteristics. Results: Of the final study population (n=38,250), 56% initiated apixaban (n=21,376; mean age: 78.6 years), 37% rivaroxaban (n=14,277; mean age: 77.4 years), and 7% dabigatran (n=2,597; mean age: 77.0 years). During follow-up, the switching rate was lowest for patients treated with apixaban at 5.2%, followed by patients treated with rivaroxaban (10.6%), and patients treated with dabigatran (16.9%, p&lt;0.001 across the 3 cohorts). Patients treated with apixaban also had the lowest discontinuation rate (63.2% vs. 68.7% vs. 71.7%, p&lt;0.001). After controlling for patient differences, those treated with rivaroxaban and dabigatran had significantly greater likelihood of switching treatment than patients treated with apixaban (Figure A). Also, rivaroxaban and dabigatran treated patients were significantly more likely to discontinue DOAC treatment (Figure B). Conclusion: Of the DOACs evaluated in this real-world study, apixaban was associated with the lowest rates of switching and discontinuation among elderly NVAF patients.

Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice. Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS. In this cohort, 411 women were included. The median age and follow-up times were 53.5years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1months for patients treated in first line, 10.5months in second line, and 4.2months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4months, respectively. The most common adverse events were hematologic, with grade 3-4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events. Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial.However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.

Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis

Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.