Drug Discontinuation Rates Research Articles

Real World Experience of Ibrutinib in an Ethnically Diverse Canadian Community Hospital

Chronic Lymphocytic Leukemia (CLL) is an indolent lymphoproliferative disorder commonly managed in community centers. Ibrutinib revolutionized the management of patients with CLL (2). Ibrutinib was initially considered an easy to administer, well tolerated oral medication with excellent efficacy. It was the first clinically available Bruton's Tyrosine Kinase (BTK) inhibitor widely used to treat CLL (3). Recently there have been concerns about cardiovascular toxicities leading to the use of alternative BTK inhibitors (5). Where alternative BTK inhibitors are available these toxicity concerns have led to a decline in the use of ibrutinib to treat CLL. The population served is ethnically diverse consisting of 52% South East Asian with a significant population of African origin. We suspected that the concerns regarding Ibrutinib toxicity were not seen in our patient population prompting a retrospective review of our experience. Ibrutinib therapy A total of 106 CLL patients treated with Ibrutinib were identified from which data was extracted. The mean age was 63.4 years. Patients with CLL treated with Ibrutinib from 2014 to 2021 were identified using OPIS and Meditech and data was extracted manually. Table 1 60% of patient received their initial drug funding through compassionate access, 2% via private insurance and the remaining 38% through the provincial health system. The majority of patients who received funding through compassionate access were eventually transitioned to the provincial health system for drug funding. Toxicity and outcomes Table 2 81% of treated patients never required a dose adjustment of Ibrutinib. The majority of dose reductions were of a temporary nature. We were unable to obtain accurate response data in our retrospective review. 82 of the 106 patients continue on ibrutinib therapy. It is presumed that these patients continue to benefit from therapy without disease progression although response data details were poorly recorded in the medical record. Conclusions There is a lack of data of community real world experience with Ibrutinib particularly in the Canadian setting. Community centers generally are lacking in information technology required to do retrospective audits. Our data shows that ibrutinib therapy for CLL is a reasonable and effective option with good tolerability in a patient population with high cardiovascular risk. The data is limited by the retrospective data collection. The efficacy of therapy is likely comparable to that of the published literature. These data suggest that the tolerability of Ibrutinib therapy seems better than that of the published literature (1) with a low incidence of atrial fibrillation, dose adjustments and low drug discontinuation rate. Of note Richter's transformation was also uncommon in our patient population. This is particularly of interest as our study did capture patients in the early days of ibrutinib therapy when there were concerns that Richter's transformation was more common than seen today. Many of the patients who were treated with ibrutinib would not have received the drug today because of cardiovascular concerns (4). At that time, it was the only available oral targeted agent for the treatment of chronic lymphocytic leukemia. Other agents such as Venetoclax, Acalabrutinib, Zanubrutinib and novel combinations were unavailable at that time or were not funded. These lack of options likely contribute to the persistence of Ibrutinib therapy in our patients. These data suggest that ibrutinib can be used in a high cardiovascular risk population with good efficacy and tolerability. 1.Alloucjery, M., Tomowiak, C., Lombard, T., & et al. (2021). Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Front Pharmacology, 12:769315. 2.Byrd, J. C., Brown, J. R., O'Brien, S., & et al. (2014). Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. NEJM, 371(3):213-223. 3.Byrd, J. C., Furman, R. R., & Coutre, S. S. (2013). Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. NEJM, 369(1):32-42. 4.Lovell, A. R., Jammal, N., & Bose, P. (2022). Selecting the optimal BTK inhibitor therapy in CLL: rationale and practical considerations. Therapueltic Advances in Hematology, 13:1177/20406207221116577. 5.Salem, J. E., Manouchehri, A., & Bretagne, M. (2019). Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. J Am Coll Cardiol, 74:1667-1678.

SAT379 Potassium Levels in Women with PCOS Using Spironolactone for Long-term

Abstract Disclosure: T.A. Oliveira: None. L.B. Marchesan: None. P.M. Spritzer: None. Introduction. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Spironolactone (SPL) has been used off-label to manage hyperandrogenic manifestations in women with PCOS but the incidence of hyperkalemia in these population is scarce. Materials and Methods. In this retrospective study, we assessed data collected from electronic medical records of women with PCOS that received spironolactone, in addition to other drugs, to manage hyperandrogenic manifestations. Women with PCOS, defined by the Rotterdam criteria, without heart or kidney disease, who were treated with SPL for a minimum of 12 months and had records of serial potassium concentrations, were included for the analyses. Mild hyperkalemia was defined as potassium concentration between 5.1 to 5.5mEq/L, moderate 5.6 to 6,0mEq/L or severe ≥ 6,0mEq/L. Results. Data from 78 women with PCOS with potassium dosages totaling 98 measurements, were analyzed. Mean age was 29.1 ± 9.6 years, BMI 32.2 ± 8.1 kg/m², 9 had Diabetes (9.2%) and 22 (22.4%) pre-diabetes. SPL was used in association with combined oral contraceptives (COCP) in 55 participants (56.1%), progestin only pill (POP) in 21 (21.4%), metformin (MTF) in 35 (35.7%) and ACEi/angiotensin receptor blockers (ARBs) in 15 (15.3%). The median SPL dose was 100mg (50 to 150mg). Ten(12,8%) women had hyperkalemia, 4 of them more than once during follow-up, all classified as mild. The most common minor adverse effects included menstrual irregular bleeding in 8 (8.2%) in 5 using POP irregularly and 3 using COCP, followed by dizziness in 6 (6.1%) and postural hypotension in 3 (3.1%). Only in two cases (2.1%) SPL was discontinued due to poor tolerance, one due to breast pain and the other due to cramps. Conclusion: The present study suggests that women with PCOS, without kidney or heart diseasee, using SPL associated with hormone contraception for managing clinical hyperandrogenism, have a low incidence of hyperkalemia, no life-threatening episodes, well-tolerated minor adverse effects and a low rate of drug discontinuation. Sources of research support: INCT/CNPq and FAPERGS. Presentation Date: Saturday, June 17, 2023

Evaluation of pentamidine tolerability and efficacy between CYP2C19 phenotypes.

Intravenous pentamidine is used for prophylaxis against Pneumocystis jirovecii pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially metabolized by CYP2C19, which is vulnerable to pharmacogenetic variation. This retrospective study evaluated allogeneic hematopoietic stem cell transplant patients who received intravenous pentamidine as P. jirovecii pneumonia prophylaxis. The primary objective was the association between CYP2C19 phenotype and discontinuation of pentamidine due to drug-related side effects based on univariate logistic regression (N=81). Ten patients (12.3%) discontinued pentamidine because of side effects. There was no difference in discontinuation between phenotype groups (p=0.18) or discontinuation due to side effects (p=0.76). Overall, no association was seen between phenotypes and pentamidine-related side effects (p=0.475). Drug discontinuation rates and P. jirovecii pneumonia infection rates were low.

Pulmonary Arterial Hypertension in the Elderly: Peculiar Features and Challenges for a Proper Phenotyping Approach.

(1) Introduction. Although pulmonary arterial hypertension (PAH) usually affects young people with a low cardiovascular risk profile, progressive epidemiologic changes have been providing a codified phenotype of elderly subjects with PAH and increased risk predictors for left heart disease. We therefore conducted a systematic review to describe the current knowledge and characteristics of elderly individuals with PAH and further insights concerning their prognostic outcomes and therapeutic response. (2) Methods. A search was conducted in PubMed, Embase, and Cochrane Library for publications evaluating the epidemiology, diagnostic work-up, and treatment of PAH in elderly subjects. (3) Among the 74 publications initially retrieved, 16 full-text articles were selected for the present systematic review. Compared to their younger counterparts, elderly individuals with PAH showed greater clinical deterioration, reduced exercise capacity, and worse prognostic outcomes, as well as less response to PAH-targeted therapy and higher rates of PAH drug discontinuation. (4) Conclusions. Demographic changes over time contributed to define a peculiar PAH phenotype in elderly patients, with an increased burden of cardiovascular comorbidities and distinctive features compared to young patients. Further investigations are needed in order to better clarify the nosologic criteria, and management in this subset population.

Real-World Safety and Efficacy of Biosimilar CT-P13 in Patients with Immune-Mediated Inflammatory Diseases: Integrated Analysis of Three Japanese Prospective Observational Studies.

Biosimilar CT-P13 was approved with limited data from clinical trials compared to the originator infliximab in biologic-naïve patients with rheumatoid arthritis. Three prospective post-marketing surveillance studies have been conducted in Japanese biologic-naïve patients and switched patients from biologics including the originator infliximab. We performed an integrated analysis of final data from three post-marketing studies to provide long-term safety and efficacy data of CT-P13 in a real-world clinical setting. A total of 1816 patients consisting of 987 patients with rheumatoid arthritis, 342 patients with Crohn's disease, 322 patients with ulcerative colitis, and 165 patients with psoriasis were evaluated for safety. Efficacy was assessed in 1150 patients whose disease parameter values were serially collected. Adverse drug reactions were reported in 24.2% of all patients. The incidence of adverse drug reactions differed by the prior treatment status with biologics: 30.5% in patients naïve to biologics, 17.0% in patients switched from the originator infliximab, and 33.5% in patients switched from other biologics. Infusion reactions were the most frequent adverse drug reactions (8.2%), and its incidence was significantly higher in patients with ulcerative colitis and an allergy history in a multivariable Cox regression analysis. Infection was the second most frequent (6.1%), but tuberculosis only occurred in four patients (0.2%). The incidence of infection was low in patients with Crohn's disease and psoriasis, and significant risk factors were an allergy history, comorbidities, and concomitant steroid use. Interstitial lung disease occurred in 16 patients (0.9%), including 11 patients with rheumatoid arthritis. With CT-P13 therapy, disease activity parameters decreased similarly in all four diseases, although long-term drug discontinuation rates because of inefficacy varied by disease. In naïve patients, the disease activity parameters decreased rapidly and the proportion of patients in remission increased. Patients switched from infliximab maintained lowered parameter levels with infliximab pretreatment. Decreases were also observed in patients switched from other biologics, but discontinuations were most often because of insufficient efficacy. The integrated analysis of a large number of patients detected no new safety signals with long-term CT-P13 treatment. Efficacy in rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis cases was confirmed in biologic-naïve patients and switched patients from the originator infliximab or other biologics.

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

ObjectivesThis multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in...

Safety and efficacy of colchicine for the prevention of post-operative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

Colchicine is an anti-inflammatory drug that may prevent post-operative atrial fibrillation (POAF). The effect of this drug has been inconsistently shown in previous clinical trials. We aimed to compare the efficacy and safety of colchicine vs. placebo to prevent POAF in patients undergoing cardiac surgery. A systematic search of EMBASE, MEDLINE, SCOPUS, ClinicalTrials.gov, and the Cochrane Library for randomized controlled trials (RCTs) was conducted from inception till April 2023. The primary outcome was the incidence of POAF after any cardiac surgery. The secondary outcome was the rate of drug discontinuation due to adverse events and adverse gastrointestinal events. Risk ratios (RR) were reported using the Mantel Haenszel method. A total of eight RCTs comprising 1885 patients were included. There was a statistically significant lower risk of developing POAF with colchicine vs. placebo (RR: 0.70; 95% CI: 0.59-0.82; P < 0.01, I2 = 0%), and this effect persisted across different subgroups. There was a significantly higher risk of adverse gastrointestinal events (RR: 2.20; 95% CI: 1.38-3.51; P < 0.01, I2 = 55%) with no difference in the risk of drug discontinuation in patients receiving colchicine vs. placebo (RR: 1.33; 95% CI: 0.93-1.89; P = 0.11, I2 = 0%). This meta-analysis of eight RCTs shows that colchicine is effective at preventing POAF, with a significantly higher risk of adverse gastrointestinal events but no difference in the rate of drug discontinuation. Future studies are required to define the optimal duration and dose of colchicine for the prevention of POAF.

432 Comparative treatment persistence of different advanced-therapies in patients with atopic dermatitis

Abstract Multiple advanced therapies are used to treat atopic dermatitis (AD), each with different efficacy, safety, tolerability, accessibility and treatment success that can affect treatment persistence. Little is known about how treatment persistence rates compare between different therapies. We compared treatment persistence for subcutaneous dupilumab, oral cyclosporine, mycophenolate, and upadacitinib, and narrowband ultraviolet B (NB-UVB) treatment of AD. A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015 to 10/1/2021. The AD cases were identified using Hanifin–Rajka criteria. Drug persistence was assessed using proportion of patients who discontinued therapy and median time to discontinuation. Chi-square tests were used to assess if there were differences in drug discontinuation rates by advanced therapy. Overall, 766 patients with AD were identified, including 139 (18.1%) prescribed dupilumab, 10 (1.3%) cyclosporine, 21 (2.7%) mycophenolate, 5 (0.7%) upadacitinib and 64 (8.4%) NB-UVB; no patients were treated with methotrexate. Drug persistence was highest for upadacitinib (100%), followed by dupilumab (86.3%), mycophenolate (38.1%), cyclosporine (30.0%) and NB-UVB (12.5%) (Chi-square, P &amp;lt; 0.0001). Highest median (days) time to discontinuation was observed with dupilumab (638), followed by cyclosporine (539), mycophenolate (274) and NB-UVB (167). Lack of efficacy was the most common reason for discontinuation of dupilumab, cyclosporine, mycophenolate and NB-UVB alike. Discontinuation due to adverse-events was highest for cyclosporine (42.9%), followed by dupilumab (31.6%), mycophenolate (30.8%) and NB-UVB (16.1%). Dupilumab had the most patients who discontinued due to disease improvement and no longer requiring advanced-therapy (21.1%). Our data suggest that drug persistence varies substantially across different advanced therapies for AD. Recently approved advanced therapies, including dupilumab and upadacitinib, showed the highest proportion of drug persistence.

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab.

Infliximab is considered superior to adalimumab in patients with ulcerative colitis, especially in severe cases. Whether this is true for Crohn disease (CD) patients with colonic involvement is unclear. Our aim was to compare the clinical effectiveness of infliximab versus adalimumab in pediatric ileocolonic (L3) CD. This retrospective study included patients <18 years with ileocolonic CD treated with infliximab or adalimumab between 2014 and 2021. Primary outcome was steroid-free clinical remission by week 52. Secondary outcomes were treatment modifications, drug discontinuation, inflammatory bowel disease (IBD)-associated hospitalizations, and surgery during the first year of treatment. We identified 74 patients treated with adalimumab and 41 with infliximab, with comparable demographic features. Concomitant immunomodulator therapy at biologic initiation was significantly lower in the adalimumab group (28% vs 85%, P < 0.001). Rates of drug intensification were higher in the infliximab group at end of induction (EOI) and at 52 weeks (55% vs 32% and 88% vs 46%, P < 0.001). Given significant differences between initial median Pediatric Crohn Disease Activity Index scores (20.0 [interquartile range, IQR 15.0-27.5] vs 11.0 [IQR 7.5-20.0] for infliximab and adalimumab groups, respectively, P < 0.001), propensity score matching was performed. Following matching, the rate of patients in steroid-free clinical remission by EOI was significantly higher in the adalimumab group (93.8% vs 46.9%, P < 0.001), but comparable by 1 year. Moreover, inflammatory markers and fecal calprotectin values were also similar at these time points. Rates of drug discontinuation, IBD-associated admissions, and surgery were similar between groups. In a retrospective study of patients with ileocolonic CD, adalimumab and infliximab had comparable outcomes by 52 weeks.

Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe.

The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naïve patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach.

P008 Hydroxychloroquine-related adverse events, attrition and reasons for cessation over 5 years at a district general hospital: estimating future ophthalmology screening service use

Abstract Background/Aims Hydroxychloroquine (HCQ) is used widely in the management of rheumatic diseases and is considered to be generally well tolerated. HCQ ocular toxicity is a dose- and time-related reaction. The Royal College of Ophthalmologists (RCOphth) noted a low rate of drug discontinuation as a result of baseline testing (&amp;lt; 4%) and that prevalence data for HCQ ocular toxicity was based on treatment duration &amp;gt;5 years. The RCOphth updated their ocular toxicity screening guideline in 2020. A major change was removal of requirement for baseline screening, with screening commenced at 5 years of treatment unless risk factors are present. Though the number of patients starting HCQ treatment and the UK prescribing data could be estimated, the proportion of patients remaining on treatment for &amp;gt;5 years was stated to be unknown. We reviewed departmental HCQ prescribing, adverse event and attrition data over 5 years from Bolton NHS Foundation Trust, a district general hospital which serves a population of nearly 300,000. Methods Patients were identified as newly commencing HCQ if they had a shared care agreement in the calendar year 2016. Adverse events, attrition rates and reasons for cessation were obtained through review of hospital records over 5 years. Results In the 2016 calendar year, 100 patients commenced HCQ. The mean age was 58, and 70% patients were female. The most common indication was rheumatoid arthritis (75%). At 1 year, 30% of patients had stopped taking HCQ. At 5 years 57% of patients had stopped taking HCQ. The most common reason for cessation at 1 year was gastrointestinal symptoms (30%), and remained the most common reason at 5 years (19%). Eye symptoms were documented as reason for cessation in 7% of patients at 1 year, and 5% of patients at 5 years. On review of records, none of these were thought to be attributable to HCQ, though it was not recommenced. There were no patient deaths directly attributable to HCQ use. Conclusion A significant proportion of patients (57%) stopped taking HCQ after 5 years. The rate of attrition was highest within 12 months, which then almost doubled by 5 years. Centres wishing to estimate the workload related to HCQ retinopathy screening can capture their prescribing for patients newly starting HCQ and/or their catchment population numbers to estimate the Ophthalmology activity related to this 5 years' hence. This may help to fund and staff adequately to successfully carry out this drug safety activity. Disclosure D. Barahman: None. C. Saleh: None. A. Paul: None.

Persistence of Biologics in the Treatment of Psoriatic Arthritis (Psa): Data From a Large Hospital Based Longitudinal Cohort.

To analyze the trends in biologics use at a specialized center over a period of 20 years. We performed a retrospective analysis of 571 patients diagnosed with PsA enrolled at the Toronto cohort who initiated a biologic therapy between January 1, 2000, and July 7, 2020. The probability of drug persistence over time was estimated nonparametrically. The time to discontinuation of first and second treatment was analyzed using Cox regression models, whereas a semiparametric failure time model with a gamma frailty was used to analyze the discontinuation of treatment over successive biologic therapy. When used as a first biologic, the highest 3-year persistence probability was observed with certolizumab, while IL-17i had the lowest probability. However, when used as second medication, certolizumab had the lowest drug survival even when accounting for selection bias. Depression and/or anxiety was associated with a higher rate of drug discontinuation due to all causes (RR 1.68, p= 0.01) while having higher education was associated with lower rates (RR 0.65, p= 0.03). In the analysis accommodating multiple courses of biologics, a higher tender joint count was associated with a higher rate of discontinuation due to all causes (RR 1.02, p=0.01). Older age at start of first treatment was associated with a higher rate of discontinuation due to side effects (RR 1.03, p=0.01) while obesity had a protective role (RR 0.56, p=0.05). Persistence on biologics depends on whether it is the first or second biologic used. Depression/anxiety, higher tender joint count, and older age lead to drug discontinuation.

Evaluating ropeginterferon alfa-2b for the treatment of adults with polycythemia vera

ABSTRACT Introduction Interferons (IFNs) have been used for decades to treat polycythemia vera (PV). Single-arm clinical trials assessing IFN in PV patients demonstrated high hematological and molecular response rates, indicating potential disease-modifying activity of IFN. However, discontinuation rates of IFNs have been rather high due to frequent treatment-related side-effects. Areas covered Ropeginterferon alfa-2b (ROPEG) is a monopegylated IFN consisting of a single isoform, which differentiates it from previous IFNs with respect to tolerability and dosing frequency. ROPEG has improved pharmacokinetic and pharmacodynamic properties, which allow extended dosing every 2 weeks and monthly administration during maintenance phase. This review covers ROPEG’s pharmacokinetic and pharmacodynamic properties, presents results of randomized clinical trials (RCT) that evaluated ROPEG in the treatment of PV patients, and discusses contemporary findings regarding the potential disease-modifying activity of ROPEG. Expert opinion RCT have demonstrated high rates of hematological and molecular responses in PV patients treated with ROPEG, irrespective of thrombotic risk. Drug discontinuation rates were generally low. However, even though RCT captured the most important surrogate endpoints of thrombotic risk and disease progression in PV, they were not statistically powered to fully determine whether therapeutic intervention with ROPEG indeed has a direct positive effect on these important clinical outcomes.

Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis

BackgroundThe routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. ObjectivesWe evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). MethodsIn this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. ResultsAmong the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). ConclusionsModerate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665)

Monotherapy with oxcarbazepine and controlled-release carbamazepine in newly diagnosed adult focal epilepsy (open comparative study)

Introduction. Oxcarbazepine is the first-line therapy for newly diagnosed focal epilepsy in children, but data on its use in adult patients in the Russian population are limited.Aim. Improvement of the efficacy of initial therapy with oxcarbazepine and controlled-release carbamazepine for newly diagnosed focal epilepsy in adults.Patients and methods. The study included 74 adult patients, 39 of them were included in the oxcarbazepine group and 35 in the controlledrelease carbamazepine group. During the 6-month follow-up period, patients completed 5 visits, during which adverse events and effectiveness were assessed, as well as video-EEG monitoring with an assessment of the epileptiform activity index. Results. The proportion of patients with a reduction in seizure frequency of more than 50 % was comparable in both groups, constituting 82.4 % (n = 28) and 85.2 % (n = 23) in the oxcarbazepine and carbamazepine group, respectively. Adverse events developed in 20 % (n = 7) of patients taking carbamazepine, and in the oxcarbazepine group in 12.8 % (n = 5) of patients. The 6-month initial monotherapy retention rate was higher in oxcarbazepine group (71.8 %) compared to carbamazepine group (65.7 %). In both groups, a 2.0–3.5-fold decrease in the average and total epileptiform activity index and epileptiform activity index during sleep was registered.Conclusions. The obtained results indicate similar effectiveness of oxcarbazepine and controlled-release carbamazepine in the treatment of newly diagnosed focal epilepsy in adults and better tolerability of oxcarbazepine in terms of both adverse events rate and lower frequency of drug discontinuation due to adverse events. A decrease in the epileptiform activity index by 2.0–3.5 times is evidence of possible use of the epileptiform activity index as an objective marker of the disease dynamics

PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials.

Chemotherapy is the standard treatment for triple-negative breast cancer (TNBC). Whether the addition of PARP inhibitors improves treatment efficacy remains controversial clinically. Thus, we performed a meta-analysis to compare the efficacy and safety of combination treatment (PC) and chemotherapy alone (CA). Relevant studies were identified through searches of 7 databases. The primary endpoints were progression-free survival (PFS) and overall survival (OS). We screened 317 studies and included seven RCTs involving 2091 patients in the final analysis. PC tended to have better efficacy than CA according to PFS (HR [hazard ratio]: 0.83 [0.75, 0.93], p = 0.001), OS (HR: 0.89 [0.76,1.03], p = 0.11) and overall response rate (ORR) (RR [risk ratio]: 1.19 [0.97,1.46], p = 0.10). However, grade 3-5 AEs (RR: 1.50 [0.87,2.61], p = 0.15) were observed in the PC group. In the PC arm, the 10 most-reported grade 3-5 AEs were neutropenia (62.8%), anemia (28.5%), thrombocytopenia (26.4%), lymphopenia (19.05%), leukopenia (16.9%), fatigue (5%), heart failure (4.76%), lung infection (4.76%), thromboembolic events (4.76%) and ventricular tachycardia (4.76%). Similar results for pathological complete response (pCR), total AEs, rate of complete response (CR), stable disease (SD) and progressive disease (PD), breast conservation rate (BCR), and drug discontinuation (DD) rate were found between the two groups. For TNBC treatment, the combination of PARP inhibitors and chemotherapy appears to be superior to chemotherapy alone with better antitumor efficacy. However, its higher rate of AEs needs to be taken seriously. More high-quality RCTs are needed to confirm these results.

Sglt-2 Inhibitors: A Useful Addition for Treatment of Heart Failure with Mildly Preserved and Preserved Ejection Fraction

Background: The use of sodium-glucose cotransporters type 2 (SGLT2) inhibitors is associated with reduction in cardiorenal outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Objective: To clarify the therapeutic role of SGLT2 inhibitors in patients with heart failure and mildly preserved ejection fraction (HFmpEF) and heart failure with preserved ejection fraction (HFpEF). Methods: Pubmed search until October 13, 2022. Search terms included: heart failure, SGLT2 inhibitors, hospitalization, mortality, safety. Randomized clinical trials and guidelines of major societies were reviewed. Results: 2 well-designed trials, the EMPEROR-Preserved and DELIVER trials, have shown that use of SGLT2 inhibitors was associated with decrease cardiac events in patients with HFmpEF and HFpEF. In the EMPEROR-Preserved, empagliflozin 10 mg/d decreased a composite primary outcome of cardiovascular (CV) death or hospitalization for heart failure (HHF) compared with placebo, hazard ratio (HR) 0.79 (95% CI, 0.69-0.90, P&lt;0.001). In the DELIVER Trial, dapagliflozin 10 mg/d decreased the primary outcome of CV death or worsening HF, HR 0.82 (95% CI 0.73-0.92, P&lt;0.001). The effects of empagliflozin and dapagliflozin on the primary outcome were evident and statistically significant versus placebo after 13-18 days post randomization. In both EMPEROR-Preserved and DELIVER trials, no significant effects on CV death were demonstrated. By pooling data from the 2 trials, the effects of empagliflozin and dapagliflozin on CV death was close but did not reach statistical significance, HR 0.88 (95% CI 0.77-1.00, P=0.052). Meanwhile, after pooling 2 dapagliflozin trials to include patients with HFrEF (DAPA-HF trial) and HFmpEF + HFpEF (DELIVER trial), dapagliflozin significantly decreased CV death, HR 0.86 (95% CI, 0.75-0.98, P=0.02) and all-cause mortality, HR 0.90 (95% CI, 0.82-0.99, P=0.03). The CV effects of empagliflozin and dapagliflozin were consistent regardless of age, gender, presence or absence of diabetes or atrial fibrillation. Yet, the effect of empagliflozin on decreasing HHF was attenuated in patients with baseline left ventricular ejection fraction (LVEF) of ≥60% and disappeared at LVEF ≥65%. On the other hand, dapagliflozin effects on cardiac outcomes remained consistent regardless of baseline LVEF. Both empagliflozin and dapagliflozin were generally well tolerated, with rates of drug discontinuation due to adverse effects similar to those with placebo. Conclusions: SGLT2 inhibitors should be the standard of care in patients with HFmpEF and HF pEF similar to their established indication in patients with HFrEF. Until direct comparison between empagliflozin and dapagliflozin becomes available, dapagliflozin should be the SGLT2 inhibitor of choice, particularly in patients with HFmpEF and HFpEF.

Withdrawal of antihypertensive medication in young to middle-aged adults: a prospective, single-group, intervention study

BackgroundAlthough antihypertensive drug therapy is commonly believed to be a life-long therapy, several recent guidelines have suggested that antihypertensive medications can be gradually reduced or discontinued for some patients whose blood pressure (BP) is well-controlled for an extended period. Thus, this pilot study aimed to describe the success rate of antihypertensive drug discontinuation over 6 months among young and middle-aged patients with hypertension.MethodsThis was a prospective, single-group, intervention study. Patients were eligible for inclusion if their cardiologist judged them to be appropriate candidates for this study, their BP had been controlled both in the office (< 140/90 mmHg) and 24-h ambulatory BP monitoring (< 135/85 mmHg) for at least 6 months with a single tablet dose of antihypertensive medication. A total of 16 patients withdrew their antihypertensive medications at baseline after they received the education, and were followed up over 6 months. After the follow-ups, six patients participated in the in-depth interview.ResultsThe likelihood of remaining normotensive at 30, 90, 180, and 195 days was 1.00, 0.85, 0.51, and 0.28, respectively. There were also no significant differences in baseline characteristics and self-care activities over time between normotensive (n = 8) and hypertensive groups (n = 8). In the interview, most patients expressed ambivalent feelings toward stopping medications. Psychological distress (e.g., anxiety) was the primary reason for withdrawal from this study although the patients’ BP was under control.ConclusionsWe found that only a limited portion of antihypertensive patients could stop their medication successively over 6 months. Although we could not identify factors associated with success in maintaining BP over 6 months, we believe that careful selection of eligible patients may increase success in stopping antihypertensive medications. Also, continuous emotional support might be essential in maintaining patients’ off-medication.

Rescue use of Pegylated Interferon in Dialysis Patient who Failed to Respond Sofosbuvir.

Rescue use of Pegylated Interferon in Dialysis Patient who Failed to Respond Sofosbuvir.

Adagrasib: A landmark in the KRASG12C-mutated NSCLC.

Adagrasib: A landmark in the KRASG12C-mutated NSCLC.