Lower Risk Of Treatment Discontinuation Research Articles

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as >5mm erythema & induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having > grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Comparative Effectiveness of Long-Acting Injectable Versus Oral Antipsychotics in Patients With Schizophrenia Using the Prevalent New User Design and Subgroup Analyses.

We compared the effectiveness of long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity. We conducted a prevalent new user cohort study using 2 administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and propensity score-matched patients on OA. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses. In total, 2520 patients using LAI and OA were identified as matched cohorts. Long-acting injectable antipsychotics were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06-1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low proportion of days covered and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30-0.89). Long-acting injectable antipsychotics were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66-0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk). Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. Long-acting injectable antipsychotics had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history.

Real-world use and clinical impact of an electronic patient-reported outcome tool in patients with solid tumors treated with immuno-oncology therapy

BackgroundUtilization of electronic patient-reported outcome (ePRO) tools to monitor symptoms in patients undergoing cancer treatment has shown clinical benefits. Tennessee Oncology (TO) implemented an ePRO platform in 2019, allowing patients to report their health status online. We conducted a real-world, multicenter, observational, non-interventional cohort study to evaluate utilization of this platform in adults with solid tumors who initiated immuno-oncology (IO) therapy as monotherapy or in combination at TO clinics.MethodsPatients initiating IO therapy prior to platform implementation were included in a historical control (HC) cohort; those initiating treatment after implementation were included in the ePRO cohort, which was further divided into ePRO users (platform enrollment ≤ 45 days from IO initiation) and non-users. Data were extracted from electronic medical records; patients were followed for up to 6 months (no minimum follow up). Outcomes included patient characteristics, treatment patterns, duration of therapy (DoT), and overall survival (OS).ResultsData were collected for 538 patients in the HC and 1014 in the ePRO cohort; 319 in the ePRO cohort were ePRO users (uptake rate 31%). Baseline age was higher, more patients had stage IV disease at diagnosis, and more received monotherapy (82 vs 52%, respectively) in the HC vs the ePRO cohort. Median follow-up was 181.0 days (range 0.0–182.6) in the HC and 175.0 (0.0–184.0) in the ePRO cohort. Median DoT of index IO regimen was 5.1 months (95% confidence interval [CI], 4.4–NE) in the HC cohort vs not estimable (NE) in the ePRO cohort. Multivariable regression adjusting for baseline differences confirmed lower risk of treatment discontinuation in the ePRO vs HC cohort: hazard ratio (HR) 0.83 (95% CI, 0.71–0.97); p < 0.05. The estimated 6-month OS rate was 65.5% in the HC vs 72.4% in the ePRO cohort (p < 0 .01). Within the ePRO cohort, DoT of index IO regimen and OS did not differ between users and non-users. In ePRO users, patient platform use was durable over 6 months.ConclusionImprovements in DoT and OS were seen after ePRO platform implementation. Conclusions are limited by challenges in separating the impact of platform implementation from other changes affecting outcomes.

Comparative Safety of Long-Acting Injectable Antipsychotics: A Systematic Review and Network Meta-Analysis.

To find the safety of long-acting injectable antipsychotics (LAIs) compared to each other, and/or placebo in the treatment of schizophrenia (SCZ) and/or schizoaffective disorder (SZA). We performed a systematic review and a network meta-analysis of randomized controlled trials (RCTs) comparing the safety of LAIs versus other LAIs or placebo in adults diagnosed with SCZ or SZA. The primary outcomes were treatment emergent adverse events (TEAEs), serious treatment emergent adverse events (STEAEs), and deaths. The secondary outcomes included treatment discontinuations due to adverse events and all-cause discontinuations. Seventeen RCTs were included (n=7,908). There were no significant differences between LAIs and placebo in the risk of presenting TEAEs. LAIs had a significant lower risk of presenting STEAEs except for aripiprazole. No significant differences in deaths were found. LAIs showed a significant protective effect against all-cause discontinuation, except for haloperidol. Only aripiprazole had a significantly lower risk of treatment discontinuation due to adverse events. We found no significant differences in the risk of presenting TEAEs between LAIs and placebo. The majority of LAIs had a significantly lower risk of presenting STEAEs than placebo. Development of international guidelines for the report of safety outcomes related to antipsychotics especially for LAIs in clinical trials could minimize report and interpretation biases and improve the accuracy of posterior meta-analysis.

Persistence and adherence with Latanoprost: A Danish register-based cohort study in older patients with glaucoma.

This study aims to assess the association between switching patterns and adherence/persistence in Danish patients over the age of 65, who started their first-ever glaucoma treatment with latanoprost eye drops. Patients were assigned to three different cohorts: (1) switchers, (2) non-switchers, and (3) preservative-free latanoprost (Monoprost®) users. Patients were followed for 1 year until the end of data coverage or censoring. Study covariates were used to compute the propensity score. In the adjusted analysis, the propensity score was added to the model as an independent variable. The Cox regression model was used to calculate the hazard ratio (HR) of discontinuation for the three cohorts (the non-switchers cohort was the reference level) in both adjusted and unadjusted analyses. Non-switchers had a statistically significant lower adherence (proportion of days covered, PDC 92%) than switchers (PDC 96%; p < 0.001) and users of Monoprost® (PDC 99%; p < 0.001). Switchers had a 53% lower risk of treatment discontinuation compared to the reference group within 1 year after the first redemption of latanoprost in both unadjusted (HR 0.47; 95% Confidence interval, 95% CI: 0.41-0.53; p < 0.001) and adjusted (HR 0.47; 95% CI: 0.42-0.53; p < 0.001) analyses. In comparison to the non-switchers, Monoprost® users had a 78% lower risk for the above result in both unadjusted (HR 0.22; 95% CI: 0.17-0.28; p < 0.001) and adjusted (HR 0.22; 95% CI: 0.17-0.29; p < 0.001) analyses. This study found increased adherence and persistence in latanoprost users among those who redeemed preservative-free latanoprost (Monoprost®) and among those who switched between different latanoprost formulations.

Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews

Background As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV. Objective To better understand the current treatment and comorbidity burden in people living with HIV (PLWH). Methods Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies. Results Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times. Conclusions There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

Cardiovascular outcomes with glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: A meta-analysis.

BackgroundAccording to available research, there have been no head-to-head studies comparing the effect of glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors on cardiovascular outcomes among patients with type 2 diabetes not reaching glycemic goal with metformin.MethodsRelevant studies were identified through electronic searches of PubMed and EMBASE published up to January 15, 2020. Efficacy outcomes of interest included the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, its individual components, all-cause death, and hospitalization for heart failure (HF). Safety outcomes included all suggested side effects of both agents previously reported.ResultsEleven studies, including 94,727 patients were used for the analysis. The risk of composite end point was significantly lower in both groups compared to the control group (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.85–0.92, p < 0.001). The risk of hospitalization for HF was significantly lower in both groups but the magnitude of the effect was more pronounced in the SGLT-2 inhibitors group (HR 0.68, 95% CI 0.60–0.76, p < 0.001) than the GLP-1 agonists group (HR 0.92, 95% CI 0.84–0.99, p = 0.03). Patients treated with GLP-1 agonists discontinued trial medications more frequently compared to conventionally treated patients because of serious side effects.ConclusionsBoth GLP-1 agonists and SGLT-2 inhibitors showed comparable cardiovascular outcomes in patients with type 2 diabetes. However, the SGLT-2 inhibitors were associated with more pronounced reduction of hospitalization for HF and lower risk of treatment discontinuation than GLP-1 agonists.

Risk of Treatment Discontinuation among Patients with Psoriasis Initiated on Ustekinumab and Other Biologics in the USA.

IntroductionBiologics are a standard therapy for patients with moderate-to-severe psoriasis, yet treatment persistence is essential to achieve disease control. Compared with other biologics, ustekinumab has been associated with lower rates of discontinuation and better adherence among patients with psoriasis, but prior studies have included limited data from the period after approval of self-administration for ustekinumab. This study was conducted to assess discontinuation risk among patients with plaque psoriasis initiating ustekinumab or other biologics.MethodsAdults with psoriasis and one or more claim for ustekinumab, secukinumab, adalimumab, or ixekizumab were identified in Optum’s de-identified Clinformatics Data Mart Database (1 January 2010 to 30 June 2019). Treatment discontinuation was defined as a gap in days of therapy supply based on (1) each drug’s per-label frequency of administration (main analysis) or (2) > 90 days (sensitivity analysis). Differences in baseline characteristics between the ustekinumab and other cohorts were adjusted with entropy balancing. Risk of discontinuation was compared with Cox proportional hazard models.ResultsOverall, 2230 patients were included in the ustekinumab cohort, with 1807 in the secukinumab, 4483 in the adalimumab, and 535 in the ixekizumab cohorts (mean age 49.0 years, 49.3% female for all cohorts). In the main analysis, risk of discontinuation for the ustekinumab cohort was 62.2% lower than for adalimumab, 46.4% lower than for secukinumab, and 43.8% lower than for ixekizumab cohorts (all p < 0.001). Sensitivity analyses revealed no significant differences between the ustekinumab and other cohorts.ConclusionsPatients with psoriasis initiating ustekinumab had lower risk of treatment discontinuation compared with other biologics when discontinuation was based on each drug’s per-label frequency of administration. This finding may help inform choice of biologic based on compliance.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00707-z.

Renal protective effect and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease and type 2 diabetes mellitus: a network meta-analysis and systematic review.

A network meta-analysis was conducted to evaluate the renal protective effect and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease and type 2 diabetes mellitus. PubMed, Embase, Cochrane Library, and Web of Science were searched by two authors using the Cochrane Collaboration risk of bias tool. Compared with controls, luseogliflozin 2.5mg (MD = -3.50, 95% CI -6.65 to -0.35), bexagliflozin 20mg (MD = -3.48, 95% CI -6.57 to -0.39), and dapagliflozin 10mg (MD = -3.08, 95% CI -5.09 to -1.06) reduced the estimated glomerular filtration rate (eGFR). Empagliflozin 25mg (MD = -240.43, 95% CI -414.13 to -66.73), dapagliflozin 10mg (MD = -94.15, 95% CI -111.72 to -76.59), and canagliflozin 100mg (MD = -193.25, 95% CI -279.16 to -107.34) reduced urine albumin-creatinine ratio levels compared with controls. Empagliflozin 25mg, canagliflozin 100mg and dapagliflozin 10mg induced a significant decline in urine albumin-creatinine ratio compared to dapagliflozin 5mg. In terms of safety, ertugliflozin 5mg reduced the risk of urinary tract infection. Compared with controls, empagliflozin 10mg and 25mg, and canagliflozin 100mg reduced the risk of any adverse events while canagliflozin 100mg reduced the risk of serious adverse events. Dapagliflozin 10mg had a lower risk of treatment discontinuation. Sodium-glucose cotransporter-2 inhibitors have favourable renal protective effect and safety; however, additional randomised clinical trials are needed to validate these findings.

Examining differences in retention on medication for opioid use disorder: An analysis of Ohio Medicaid data

BackgroundMedications for opioid use disorder (MOUDs), including methadone, buprenorphine and naltrexone, are associated with lower death rates and improved quality of life for people in recovery from opioid use disorder (OUD). Less is known about each MOUD modality's association with treatment retention and the contribution of behavioral health therapy (BHT). The objectives of the current study were to estimate the association between MOUD type and treatment retention and determine whether BHT was associated with length of time retained. MethodsWe investigated the time from initiation to discontinuation from MOUD by medication type and exposure to BHT using statewide Medicaid Claims data (N = 81,752). We estimated covariate adjusted hazard ratios (AHR) using a Cox proportional hazards model. ResultsCompared to methadone, buprenorphine was associated with a higher risk of discontinuation at the time of initiation (AHR = 2.41, 95% CI = 2.28–2.55), however that difference decreased over one year of maintained retention (AHR = 1.44, 95% CI = 1.37–1.50). Compared to methadone and buprenorphine, naltrexone was associated with a higher risk of discontinuation at the time of initiation (naltrexone vs. methadone AHR = 2.49, 95% CI = 2.30–2.65; naltrexone vs. buprenorphine AHR 1.03, 95% CI = 1.00–1.07), and that relative risk increased over the course of one year of retention (naltrexone vs. methadone AHR = 3.85, 95% CI = 3.63–4.09; naltrexone vs. buprenorphine AHR = 2.67, 95% CI = 2.54–2.81). In general, independent of MOUD type, exposure to BHT during MOUD treatment was associated with a lower risk of discontinuation (AHR = 0.94, 95% CI = 0.92–0.96). However, BHT during the treatment episode was not associated with retention in the adolescent/young adult and pregnant women subpopulations. DiscussionFrom the standpoint of early success, methadone was associated with the lowest risk of treatment discontinuation. While buprenorphine and naltrexone were associated with similar risks at the beginning of treatment, the relative discontinuation risk for buprenorphine was less than half that of naltrexone at one year of retention. In general, BHT with MOUD was associated with a lower risk of treatment discontinuation.

Real-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIs

Back to table of contents Previous article Next article Clinical & ResearchFull AccessReal-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:8 Oct 2021https://doi.org/10.1176/appi.pn.2021.9.32AbstractAn analysis of national VA health databases shows clozapine along with long-acting formulas of aripiprazole and paliperidone have lower discontinuation rates than oral olanzapine, while oral quetiapine and ziprasidone have higher discontinuation rates.Patients with schizophrenia may be less likely to discontinue treatment if prescribed clozapine or long-acting injectable (LAI) formulations of second-generation antipsychotics, according to a report in AJP in Advance. The findings, which also revealed that patients who were taking multiple antipsychotics (polypharmacy) had lower discontinuation rates, were based on data from the U.S. Department of Veterans Affairs (VA).Though the data was limited to veterans, lead author Marc Weiser, M.D., head of the Division of Psychiatry at Sheba Medical Center in Ramat Gan, Israel, noted the findings mirrored those of a 2017 study that used Swedish medical data. “Replicating research findings is difficult,” Weiser noted. “When you have nearly identical outcomes from two studies done by different investigators in different countries using different patient populations, it points to the results being broadly applicable.”Weiser and colleagues compiled VA clinical and pharmacy data from all patients who received a schizophrenia diagnosis and at least one antipsychotic prescription lasting 60 days or more between October 2010 and September 2015. To keep the data robust, the investigators focused on antipsychotics with at least 150 prescriptions during the analysis period. The final sample included 37,368 patients with 62,056 antipsychotic prescriptions among 15 categories: nine oral medications (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and all first-generation antipsychotics), five LAI formulations (first-generation drugs fluphenazine and haloperidol and second-generation aripiprazole, paliperidone, and risperidone), and patients receiving polypharmacy.The investigators compared the treatment discontinuation rates and hospital admission rates associated with all the medications relative to olanzapine. Weiser noted olanzapine was chosen as the reference since it is considered the most well-tolerated oral antipsychotic and it was used as the reference drug in the 2017 Swedish study.After adjusting for patient sociodemographic factors, Weiser and colleagues found that five groups had a lower risk of treatment discontinuation than olanzapine. These included patients taking clozapine (with nearly 60% less discontinuation risk than olanzapine), a trio of second-generation LAIs (aripiprazole, paliperidone, and risperidone), and patients on polypharmacy. Patients taking oral quetiapine, oral ziprasidone, oral aripiprazole, oral risperidone, and oral first-generation antipsychotics all had higher risks of discontinuation than those taking olanzapine. In a secondary analysis, the investigators found that all three second-generation LAIs were associated with lower risks of discontinuation with the oral formulations of the medications.Weiser told Psychiatric News that he was not surprised by the findings that clozapine was associated with a lower risk of treatment discontinuation than the other antipsychotics. “Since clozapine requires patients to check in regularly, physicians tend to prescribe it to patients who they believe will be compliant; there is a pre-screening process built in.”The polypharmacy findings were a bit more surprising, he noted. “Giving patients multiple antipsychotics is considered a no-no in clinical settings, but this finding supports that giving the right combination of drugs can boost their effectiveness,” he said. Future studies should look at which combinations may offer the most symptom improvement along with lowest risks of side effects.In contrast to the discontinuation findings, none of the medications were found to reduce the risk of psychiatric hospitalization compared with olanzapine. Weiser noted this was the one of the few divergences from the Swedish study, which found clozapine to be superior to olanzapine.While no antipsychotics were superior to olanzapine in terms of hospitalizations, several were associated with increased hospitalization risk: these included oral and LAI first-generation antipsychotics, as well as oral lurasidone, quetiapine, and ziprasidone.Weiser noted that he was particularly concerned about the quetiapine finding, being that this was the second most-prescribed medication in the sample (behind oral risperidone) and this medication was associated with a 36% increased risk of hospitalization. “It is interesting since in the general population, quetiapine is not used that extensively for schizophrenia,” he said. Rather, quetiapine is more commonly prescribed off-label for conditions like anxiety or insomnia.This study was supported by the Stanley Medical Research Institute. Weiser also serves on the staff of the Stanley Institute. ■“Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs” is posted here.The 2017 analysis, “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” is posted here. ISSUES NewArchived

Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis

BackgroundReal-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion.Research questionThe data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015–2016.Study design and methodsPatients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period.ResultsDuring the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3–2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0–1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6–0.9).InterpretationThis observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

Real-World Treatment Persistence with Biologic Disease-Modifying Antirheumatic Drugs Among German Patients with Psoriatic Arthritis-A Retrospective Database Study.

IntroductionTo investigate drug survival for biologic disease-modifying antirheumatic drugs (bDMARDs) in a real-world cohort of German adult biologic-naïve patients with psoriatic arthritis (PsA).MethodsClaims data for patients with a diagnosis of PsA, a bDMARD claims record (index date) between 1 January 2014 and 31 December 2017, and no bDMARD prescription for 365 days before the index date were retrospectively analyzed. The primary outcomes were the overall and individual bDMARD persistence rates over 12 months. Nonpersistence was defined as a treatment gap exceeding the days of supply plus 60 days or switching to a bDMARD other than the index therapy. Sensitivity analysis was performed, wherein the treatment gap was found to vary depending on the bDMARD regimen. Kaplan–Meier curves were plotted to determine persistence; the log-rank test was used to evaluate differences in the persistence rate. Factors associated with treatment discontinuation were evaluated using Cox regression analysis.ResultsAmong 10,954 patients with a PsA diagnosis, 348 were eligible. The overall bDMARD persistence rate was 57.5%; individual bDMARD persistence rates were 81.3% for ustekinumab, 66.7% for infliximab, and 60.0% for golimumab. The mean (SD) overall persistence with bDMARDs was 289 (103) days; the mean persistence was 334 (72) days for ustekinumab, 309 (82) days for golimumab, and 305 (92) days for infliximab. The main reasons for nonpersistence were switching to another bDMARD (15.8%) and treatment discontinuation (26.7%). Male gender was significantly associated with a lower risk of treatment discontinuation (hazard ratio 0.54, 95% confidence interval 0.39–0.77; P < 0.001). The sensitivity analysis yielded similar results.ConclusionThe one-year persistence rate for bDMARDs in German PsA patients is modest, although the persistence rate depends on the bDMARD considered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00286-z.

Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data.

IntroductionAlthough clinical guidelines are broadly available, the relationship between adherence and outcomes is not well studied. This study aimed to assess the association between adherence to National Comprehensive Cancer Network (NCCN) guidelines and clinical outcomes for adult patients with advanced non-small-cell lung cancer (aNSCLC).MethodsThis was a retrospective cohort study of adult patients with aNSCLC (stages IIIB, IIIC, and IV) from a de-identified real-world database. The objective was accomplished in a two-step analysis process. We first assessed adherence to NCCN recommendations for biomarker testing and overall survival (OS). Next, we assessed adherence to NCCN-recommended first-line therapy and time to treatment discontinuation (TTD). Multivariable Cox regression analyses were conducted to evaluate the association between guideline adherence and patient outcomes. Kaplan–Meier analyses were used to assess median OS and TTD.ResultsA total of 28,784 patients with a diagnosis for aNSCLC between January 1, 2011 and July 31, 2019 met the inclusion criteria for the analysis of NCCN-recommended biomarker testing adherence. Two-thirds of these patients (n = 19,787) had evidence of biomarker testing (adherent). Multivariable Cox models found that testing-adherent patients had a significantly lower risk of mortality [hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.86, 0.92; p < 0.01]. Median OS was modestly longer in the testing-adherent group compared to the testing-non-adherent group (15.4 vs. 14.2 months; p < 0.01). For the first-line therapy analysis, 15,898 patients met the inclusion criteria, of which 69.9% had evidence of appropriate first-line therapy (first-line-adherent). The multivariable Cox model found that adherent patients had significantly lower risk of treatment discontinuation versus non-adherent patients (HR = 0.60, 95% CI 0.57, 0.62; p < 0.01). First-line-adherent patients had a modest, yet significantly longer median TTD compared to first-line-non-adherent patients (3.45 vs. 2.40 months; p < 0.01).ConclusionsImproved clinical outcomes were observed in patients who were adherent to NCCN-recommended biomarker testing and first-line therapy. This study demonstrated the value of following NCCN guideline recommendations and the need to prioritize timely access to biomarker testing and individualized treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-020-01617-2.

Adverse events associated with peanut oral immunotherapy in children \u2013 a systematic review and meta-analysis

While peanut oral immunotherapy (POIT) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4–9.0; 27 studies, I2 = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5–11.4; 26 studies, I2 = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8–3.7; 15 studies, I2 = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.

Efficacy of tapentadol prolonged release for pre- and post-operative low back pain: a prospective observational study.

Low back pain (LBP) is a highly prevalent chronic pain condition with a neuropathic component of pain that limits the benefits of classical opioids. Tapentadol is an innovative drug for the treatment of chronic severe pain, with a dual mechanism of action combining µ-opioid receptors agonism and noradrenaline re-uptake inhibition (NRI). Its efficacy is equal to that of strong opioids, with a better tolerability profile and a consequently lower risk of treatment discontinuation. The aim of this study was to evaluate the analgesic efficacy and tolerability of tapentadol prolonged release (PR) vs. other analgesics in patients with moderate-to-severe neuropathic low back pain, before and after back surgery. The primary endpoints of the study were the rate of response to treatment, measured as ≥30% reduction in pain intensity on the Numeric Rating Scale (NRS), and tapentadol PR efficacy for pain relief. The secondary endpoints were the improvements of the neuropathic component of pain and of sleep quality. A total of 40 patients were enrolled in the study, receiving either tapentadol PR (n=21, 52.5%) or other analgesics (n=19, 47.5%), both before and after surgery. The rate of response to treatment was statistically in favor of tapentadol PR (p<0.01). The reduction in pain intensity was statistically significant in the group treated with tapentadol PR, both before and after surgery (p<0.01), with a complete resolution of pain 90 days after surgery. The quality of sleep after surgery improved more in patients treated with tapentadol PR than in the comparator group (p<0.01), with 100% of the patients reporting a "good" sleep quality 2 months after surgery. Tapentadol PR was well tolerated by all patients, and its efficacy for pain relief was also confirmed in our small group of "real-life" patients with chronic, severe low back pain. Overall, the tolerability of this treatment may help to improve patients' quality of life, which is frequently compromised because of pain and its related comorbidities.

Comparison of efficacy and tolerability of azathioprine, mycophenolate mofetil, and cyclophosphamide among patients with neuromyelitis optica spectrum disorder: A prospective cohort study

AimsTo compare the efficacy and tolerability of azathioprine (AZA), mycophenolate mofetil (MMF), and cyclophosphamide (CTX) in patients with neuromyelitis optica spectrum disorder (NMOSD). MethodsWe performed a prospective cohort analysis of relapses, disability, and adverse events in NMOSD patients treated with AZA, MMF, or CTX (n=119, 38, and 41, respectively). All the patients were co-treated with oral prednisone. ResultsA significant reduction in relapse rate was found in patients taking AZA (p<0.001), MMF (p<0.001) or CTX (p=0.01). MMF was associated with a lower risk of relapse than AZA, but this difference was not statistically significant (p=0.08). AZA and MMF decreased the mean Expanded Disability Status Scale (EDSS) scores significantly (AZA: p=0.02; MMF: p=0.01), whereas CTX did not. Compared with AZA, MMF had a significantly lower risk of treatment discontinuation due to drug-related adverse events (p=0.02), whereas CTX had a comparable risk (p=0.35). ConclusionsMMF is a good first-line treatment option for NMOSD and AZA remains a valuable first-line drug if its side effects are tolerable while CTX can be a treatment option for patients who cannot tolerate AZA and MMF.

Implication of different initial beta blockers on treatment persistence: atenolol vs new‐generation beta blocker, a population‐based study

Potential heterogeneity within the same class of drug in terms of persistence may lead to different clinical implications. Given that the increased risks of mortality and cardiovascular events are due, in part, to the lack of persistent use of antihypertensive medications, the objective of this study was to evaluate 1-year persistence of new-generation beta blockers compared to atenolol in antihypertensive treatment-naïve patients. A total of 9978 patients aged 18years or older with hypertension newly diagnosed in 2012, without hypertension-related complication and initiated treatment with beta blocker monotherapy during 2012 were included in the analysis. Rate and duration of treatment and drug persistence were compared between atenolol and new-generation beta blockers. Hazards of discontinuation in nonatenolol compared to atenolol were evaluated using a multivariate Cox proportional model. The rate of treatment persistence was higher in the nonatenolol group (57.35% vs 53.40%, P<.0001), and the time to treatment discontinuation was earlier in the atenolol group with a minimal difference in the average (243.2 vs 254days, P<.0001). New-generation beta blockers demonstrated a lower risk of treatment discontinuation (HR: 0.91, 95% CI: 0.86-0.96) compared to atenolol; a notable improvement was observed with carvedilol and nebivolol (HR: 0.74, 95% CI: 0.69-0.80 and HR: 0.79, 95% CI: 0.70-0.89, respectively), whereas betaxolol showed a substantially greater hazard for discontinuation compared to atenolol. This study demonstrated a meaningful improvement in treatment persistence with new-generation beta blockers compared to atenolol, with betaxolol as exception.

Age-related differences in persistence in women with breast cancer treated with tamoxifen or aromatase inhibitors in Germany.

To study age-related persistence in postmenopausal women with endocrine-responsive breast cancer treated with tamoxifen (TAM) and aromatase inhibitors (AI). Data on 29,245 patients diagnosed with metastatic or non-metastatic breast cancer (BC) and initially treated with TAM or AI between 2004 and 2013 were included. The primary outcome measure was the age-dependent rate of discontinuation of endocrine treatment within 5years after initiation. Discontinuation of therapy was defined as a period of at least 90days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance type (private/statutory), type of care (gynecological/general), region (West/East Germany), concomitant diagnoses (depression, osteoporosis, and diabetes), and Charlson Comorbidity Score were included as covariates. The mean ages of the women in the <70 and ≥70 groups were 55.9 (SD: 9.7) and 77.4 (SD: 5.4) years, respectively. Within 5years after treatment initiation, 88.8% of women <70 of age and 82% of women ≥70 years of age had terminated treatment (p-value<0.001). Patients aged ≥70 exhibited a lower risk of treatment discontinuation than patients aged <70 (HR=0.75, 95% CI: 0.66-0.85). Furthermore, gynecological practices, disease management programs, and high Charlson scores increased persistence. Overall, the present study indicates that persistence rates are low in both women with BC aged <70 and those aged ≥70 years. We also found that younger women with BC are at a higher risk of treatment discontinuation than older women.

Age-related differences in persistence with bisphosphonates in women with metastatic breast cancer

AimsTo investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. MethodsWe included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance coverage (private/statutory), type of care (gynecological/general), region (West/East Germany), depression, chemotherapy, hormone therapy, pain medication, antidepressants, and the number of co-medications were included as covariates. ResultsThe mean ages in the group of women <70 and that of women ≥70 years of age were 55.7 (SD: 9.8) and 76.7 (SD: 5.1) years respectively. Within 12 months after treatment initiation, 44.3% of women <70 and 34.8% of women ≥70 had terminated treatment (p-value<0.001). Patients aged ≥70 were at a lower risk of treatment discontinuation than patients <70 (HR=0.78, 95% CI: 0.67–0.91). Furthermore, treatment in gynecological practices, chemotherapy, hormone therapy, pain medication, and number of co-medications decreased the risk of discontinuation. By contrast, residing in West Germany and private health insurance coverage increased discontinuation risk. ConclusionsWomen with metastatic BC aged ≥70 are at a lower risk of BIS treatment discontinuation than younger women.