Lower Risk Of Discontinuation Research Articles

Blunt smoking during emerging adulthood: Characterizing transitions in cannabis and cigar co-use among a diverse cohort in Texas

ObjectiveTo characterize and compare transitions in blunt smoking behaviors among a diverse cohort of youth and young adults observed between Spring 2019 and Fall 2021. MethodsWe analyzed n = 14,152 observations (i.e., completed surveys) provided by n = 2,610 youth and young adults over six (6) waves from Spring 2019 to Fall 2021 via the Texas Adolescent Tobacco and Marketing Surveillance (TATAMS) system. Participants were recruited in age-cohorts, reflecting 16.5 years (0.5), 18.5 years (0.6), and 20.1 years (0.8) of age at baseline. We applied a three-state Markov model to estimate blunt initiation (never → ever), onset (never → current), continuation (ever → current), and discontinuation (current → ever). First, we compared transitions in blunt smoking by race/ethnicity, with non-Hispanic (NH) Whites as the referent. Second, we stratified the Markov models by race/ethnicity to identify common and unique predictors of blunt transitions, including sex, age, alcohol use, depression, anxiety, and tobacco cigar smoking. ResultsAt baseline, 73% of participants had never smoked blunts, 15.3% had ever smoked blunts s, and 11.7% currently smoked blunts. NHB (HR: 2.15; 95% CI: 1.21–3.84) and Hispanic (HR: 1.72; 95% CI: 1.08–2.72) participants had significantly greater risk of blunt smoking initiation, relative to NHWs. Similarly, NHBs had great risk for continuation (HR: 1.65; 95% CI: 1.16–2.34) and lower risk of discontinuation (HR: 0.57; 95% CI: 0.42–0.77), relative to NHWs. Alcohol use predicted greater risk for onset among NHW (HR: 5.22; 95% CI: 1.40–19.45), NHB (HR: 3.14; 95% CI: 1.32–7.46), and Hispanic (HR: 2.99; 95% CI: 1.80–4.97) participants. ConclusionsBlunt smoking initiation was most common among NHB and Hispanic youth and young adults while risk for sustained blunt smoking was higher in NHB youth and young adults. Research and interventions should investigate the link between alcohol use and elevated blunt smoking among young people.

Treatment modification after initiating second-line medication for type 2 diabetes.

To describe changes in antidiabetic medication (ADM) use and characteristics associated with changes in ADM use after initiation of noninsulin second-line therapy. Retrospective cohort study. This study analyzed private health plan claims for adults with type 2 diabetes who initiated 1 of 5 index ADM classes: sulfonylureas, dipeptidyl peptidase 4 inhibitors (DPP4is), sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or thiazolidinediones. Analyses evaluated 3 treatment modification outcomes-discontinuation, switching, and intensification-over 12-month follow-up. Of 82,624 included adults, nearly two-thirds (63.6%) experienced any treatment modification. Discontinuation was the most common modification (38.6%), especially among patients prescribed GLP-1 RAs (50.3%). Switching occurred in 5.2% of patients and intensification in 19.8%. In adjusted analysis, compared with patients prescribed sulfonylureas, discontinuation risk was 7% higher (HR, 1.07; 95% CI, 1.04-1.10) among patients prescribed DPP4is and 28% higher (HR, 1.28; 95% CI, 1.23-1.33) among patients prescribed GLP-1 RAs. Compared with sulfonylureas, all other index ADM classes had higher risks of switching and lower risks of intensification. Younger age group and female sex were both associated with higher risks of all modifications. Compared with index ADM prescription by a family medicine or internal medicine physician, index prescription by an endocrinologist was associated with both lower discontinuation risk and higher intensification risk. Most patients experienced a treatment modification within 1 year. Results highlight the need for new prescribing approaches and patient supports that can maximize medication adherence and reduce health system waste.

Adherence and persistence of HIV pre-exposure prophylaxis use in the United States.

To describe medication adherence and persistence of HIV PrEP overall and compare between sex and age groups of commercially insured individuals in the United States. We conducted a national retrospective cohort study of the Merative MarketScan Claims Database from 2011 to 2019 to describe adherence and persistence of PrEP overall and compared between sex and age groups. High adherence was defined as ≥80% of proportion of days covered and persistence was measured in days from initiation to the first day of a 60-day treatment gap. A total of 29 689 new PrEP users identified. Overall adherence was high (81.9%; 95% confidence interval [CI]: 81.5%-82.3%). Females were more adherent than males (adjusted odds ratio [aOR] 1.87; 95% CI: 1.50-2.34), while those ≥45-years were less adherent than individuals <45-years (aOR 0.87: 95% CI: 0.81-0.93). More than half of individuals discontinued therapy within the first year (median 238.0 days; interquartile range 99.0-507.0 days). Females were less persistent than males (hazard ratio [HR] 1.49; 95% CI: 1.34-1.65), and people ≥45-years old were more persistent (i.e., lower risk of discontinuation) than those <45-years (HR 0.43; 95% CI: 0.33-0.55). These findings show adherence to daily PrEP is high among commercially insured individuals but the majority still discontinue in the first year. Future research should investigate what factors influence PrEP discontinuation among this population and ways to reduce barriers to therapy maintenance to ensure the population-level benefits of PrEP treatment.

Oral Pre-Exposure Prophylaxis for HIV Discontinuation in a Large Cohort of Adolescent Men Who Have Sex With Men and Transgender Women in Brazil

PurposeThis study aimed to describe pre-exposure prophylaxis (PrEP) for HIV discontinuation in adolescent men who have sex with men (aMSM) and adolescent transgender women (aTGW) and to identify factors associated with discontinuation. MethodsThe PrEP1519 study included a cohort of aMSM and aTGW aged 15–19 years old, and it was conducted in three large Brazilian capital cities. For this analysis, we included adolescents who initiated PrEP. PrEP discontinuation was defined as no possession of PrEP pills for >90 days. Kaplan-Meier curves were used to analyze the probabilities of discontinuation, and survival distributions stratified by covariates were compared using log-rank or Wilcoxon tests. Cox regression models were used to estimate the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). ResultsWe included 908 adolescents, 829 (91.30%) aMSM and 79 (8.70%) aTGW, most of whom were 18–19 years (80.29%). The incidence rate of discontinuation was 75.6 per 100 person-years. The probability of discontinuation was 52.61% in the first year. The multivariate analysis demonstrated that the aTGW (aHR = 1.63; 95% CI: 1.02–1.64) and adolescents with a medium (aHR = 1.29; 95% CI: 1.02–1.64) or low (aHR = 1.65; 95% CI: 1.29–2.12) perceived risk of HIV infection had an increased risk of discontinuation, whereas the adolescents with a partner living with HIV had a lower risk of discontinuation (aHR = 0.57; 95% CI: 0.35–0.91). DiscussionAdolescents with a high risk for discontinuation may need additional support that emphasizes the value of PrEP as a tool for HIV prevention because PrEP discontinuation was associated with a disconnect between HIV risk perception and HIV prevention.

Real-world comparative effectiveness of acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia

AbstractNovel agents, including Bruton tyrosine kinase inhibitors (BTKis), have become the standard of care for patients with chronic lymphocytic leukemia (CLL). We conducted a real-world retrospective analysis of patients with CLL treated with acalabrutinib vs ibrutinib using the Flatiron Health database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1 January 2018 and 28 February 2021. The primary outcome of interest was time to treatment discontinuation (TTD). Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional hazards model was used to compare the TTD between cohorts. Of the 2509 patients included in the analysis, 89.6% received ibrutinib, and 14.1% received acalabrutinib. TTD was not significantly different between cohorts in the unweighted analysis. After weighting, the cohorts were balanced on all baseline characteristics except cardiovascular risk factors and baseline medications use. The median (95% confidence interval [CI]) TTD was not reached (NR; 95% CI, 25.1 to NR) for the acalabrutinib cohort and was 23.4 months (95% CI, 18.1-28.7) for the ibrutinib cohort. The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = .005). After additional adjustment for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs ibrutinib (hazard ratio, 0.59; 95% CI, 0.43-0.81; P = .001). In the largest available study comparing BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs those receiving ibrutinib.

Long-Term Real-World Effectiveness of Aripiprazole Once-Monthly. Treatment Persistence and Its Correlates in the Italian and Spanish Clinical Practice: A Pooled Analysis.

BackgroundOne of the most significant risk factors for relapse and hospitalization in schizophrenia is non-adherence to antipsychotic medications, very common in patients with schizophrenia. The aim of this analysis was to evaluate the treatment persistence to aripiprazole once-monthly (AOM) and the factors affecting it in the pooled population of two similar studies performed previously in two different European countries.MethodsPooled analysis of two non-interventional, retrospective, patient record-based studies: DOMINO and PROSIGO. Both analyzed treatment persistence after starting AOM treatment in the real-world setting. The primary variable was persistence with AOM treatment during the first 6 months after treatment initiation. A multivariate Cox regression model was used to evaluate the influence of several baseline characteristics on the persistence.ResultsThe study population comprised 352 patients included in the two studies, DOMINO (n = 261) and PROSIGO (n = 91). The overall persistence with AOM treatment at the end of the 6-month observation period was 82.4%. The multivariate analysis showed that patients with “secondary school” level of education present a 67.4% lower risk of discontinuation within 6 months after AOM initiation when compared with “no/compulsory education patients” (p = 0.024). In addition, patients with an occupation present a 62.7% lower risk of discontinuation when compared with unemployed patients (p = 0.023). Regarding clinical history, patients with a Clinical Global Impression—Severity scale (CGI-S) score ≤3 present a 78.1% lower risk of discontinuation when compared with patients with a CGI-S score ≥6 (p = 0.044), while patients with a time since schizophrenia diagnosis ≤8.4 years present a 52.9% lower risk of discontinuation when compared with the rest of patients (p = 0.039).ConclusionThe AOM persistence rate observed in this study was 82.4%, which was higher than that reported in clinical trials, aligned with other real-life studies and higher than reported for other long-acting injectable antipsychotics. The persistence rate was high in complex patients, although patients with higher level of education, active occupation, lower initial CGI-S score and shorter time since the diagnosis of schizophrenia appear to be more likely to remain persistent with AOM during the 6 months after initiation.

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.

Comparison of Real-World Treatment Patterns Among Biologic-Experienced Patients with Psoriasis Treated with Ixekizumab or Secukinumab Over 18Months.

IntroductionReal-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA.MethodsA retrospective observational study using administrative claims data from IBM® Watson Health MarketScan® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching.ResultsOverall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05–1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68–0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68–0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60–0.93).ConclusionThis study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment.

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

Persistence of antidepressant use among refugee youth with common mental disorder

BackgroundThe objective of this study was to investigate whether persistence of antidepressant use differs between refugee youth and Swedish-born youth after a diagnosis of a common mental disorder (CMD), and if clinical and sociodemographic factors are associated with antidepressant discontinuation. MethodsYouth aged 16-25 years, with an incident diagnosis of CMD (depression, post-traumatic stress disorder (PTSD), anxiety disorders) accessing specialized healthcare in Sweden 2006-2016 were included. New users were identified with a one-year washout period. Refugees (N=1575) were compared with Swedish-born youth (N=2319). Cox regression models [reported as adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs)] were used to investigate factors associated with discontinuation of antidepressant use. ResultsAmong youth (mean age 20.9 years, SD 2.7, 50% females), the median duration of antidepressant use differed considerably between refugee (101 days, IQR 31-243) and Swedish-born youth (252 days, IQR 101-558). Refugees were more likely to discontinue treatment (HR 1.61, 95% CI 1.47-1.77). Factors associated with an increased risk for discontinuation in refugees included ≤5 years duration of formal residency (HR 1.28, 95% CI 1.12-1.45), antidepressant type, and dispensing lag (time from prescription to dispensing) of >7 days (1.43, 1.25-1.64), whereas PTSD (0.78, 0.64-0.97) and anxiolytic use (0.79, 0.64-0.96) were associated with a lower discontinuation risk. LimitationsOnly persons treated in specialized healthcare could be included. ConclusionThe relatively short treatment durations among refugee youth suggest that antidepressant treatment may not be optimal in CMD, and better monitoring of treatment as well as transcultural education of healthcare personnel are warranted.

Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting

BackgroundIncreasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting. MethodsWe compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion. ResultsMost neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p < 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p < 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p < 0.0001). ConclusionsFunding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

Comparison of two-year treatment adherence, persistence, discontinuation, reinitiation, and switching between psoriasis patients treated with ixekizumab or secukinumab in real-world settings

Real-world data on long-term treatment patterns associated with interleukin-17A inhibitors in plaque psoriasis are lacking. To compare ixekizumab or secukinumab treatment patterns over a 24-month period among plaque psoriasis patients. Adult patients with psoriasis who had 1 or more claims for ixekizumab or secukinumab between March 1, 2016, and October 31, 2019, and with 24months of follow-up after starting treatment were identified from IBM MarketScan claims databases. Inverse probability of treatment weighting and multivariable models were employed to balance cohorts and estimate the risks of nonpersistence, discontinuation, and switching and odds of highly adherent treatment (proportion of days covered≥80%). A total of 471 ixekizumab and 990 secukinumab users were included. Compared to secukinumab, ixekizumab use was associated with a 20% lower risk of nonpersistence (hazard ratio, 0.80; 95% CI, 0.70-0.92), a 17% lower risk of discontinuation (hazard ratio, 0.83; 95% CI, 0.72-0.96), and a 42% higher odds of being highly adherent to treatment (odds ratio, 1.42; 95% CI, 1.12-1.80). No difference in risk of switching was observed (hazard ratio, 0.83; 95% CI, 0.68-1.01). Disease severity and clinical outcomes were unavailable. Over 24months, ixekizumab users exhibited better persistence and adherence, and a lower risk of discontinuation than secukinumab users in real-world settings.

Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry

Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug’s overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan–Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan–Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99–1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54–0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00–1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15–1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05–1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00–1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12–1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases.

Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study.

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78 p = 0.001), obesity (HR 0.53, 95% CI 0.30-0.93 p = 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93 p = 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99 p = 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34 p = 0.011 and HR 2.53, 95% CI 1.61-3.96 p < 0.001).Conclusions: SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.

Real-world discontinuation rate of teriflunomide and dimethyl fumarate in multiple sclerosis.

BackgroundFor patients with MS, medication switches increase the risk of disease reactivation.ObjectiveCompare discontinuation rates due to treatment failure or side effects between teriflunomide and dimethyl fumarate, and investigate clinical variables affecting discontinuation rates.MethodsAll patients who received teriflunomide or dimethyl fumarate at Haukeland University Hospital from 2013 until 2018 were identified. Clinical and demographic variables were extracted from the Norwegian MS Registry. Cause-specific Cox regression models estimated the rate of discontinuation due to treatment failure or side effects.ResultsWe included 354 patients treated with either dimethyl fumarate (n = 185) or teriflunomide (n = 169). We found 38% lower risk of discontinuation because of treatment failure for patients using dimethyl fumarate compared to teriflunomide (p < 0.05). In a treatment-naive subgroup (n = 183), we found a 38% reduced risk of discontinuation for any reason among patients using dimethyl fumarate (p < 0.05). There was no significant difference between treatment groups in discontinuation rate due to side effects, although more patients reported side effects when treated with dimethyl fumarate.ConclusionOur findings suggests that dimethyl fumarate has a lower risk of discontinuation because of treatment failure among both treatment-experienced and treatment-naive patients.

Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry.

To compare drug survival of ixekizumab to other IL‐17 inhibitors (IL‐17i) and TNF inhibitors (TNFi) among patients with psoriasis (PsO) in a real‐world setting. Participants included adult PsO patients enrolled in the Corrona Psoriasis Registry who initiated ixekizumab, TNFi, or other IL‐17i between 16 March 2016 to 10 August 2019 and completed ≥1 follow‐up visit. Multivariable adjusted hazard ratios (HR) were calculated to estimate the risk for drug discontinuation in the ixekizumab group relative to the other drugs. Among the 1604 drug initiations, 552 initiated ixekizumab, 450 initiated TNFi, and 602 initiated other IL‐17i. Mean age was 51 years, 49% were women, and 52% were obese (BMI > 30). Ixekizumab patients had a higher proportion of patients with PASI >12 at drug initiation (24%) than TNFi (15%) and other IL‐17i (19%). Over a median of 11 months of follow‐up, 723/1604 (45%) drug discontinuations occurred. Persistence of ixekizumab, TNFi, and other IL‐17i at 24‐months were 68%, 33%, and 46%, among biologic‐naïve patients (n = 543), and 46%, 23%, and 36%, for biologic‐experienced patients (n = 1061), respectively. Ixekizumab patients had a 64% lower risk of discontinuation vs TNFi (HR = 0.36; 95% CI 0.27‐0.47) and a 31% lower risk vs other IL‐17i (HR = 0.69, 95% CI 0.55‐0.87) after adjustment for biologic experience and other covariates. HRs were similar when limited to patients with moderate‐to‐severe PsO (BSA > 3, PASI > 3, and IGA > 1, n = 1076) at initiation. In our study of real‐world patients with PsO, initiators of ixekizumab had more prolonged drug survival than both initiators of TNFi and other IL‐17i up to 2 years of follow‐up.

Measuring Service Quality and Assessing Its Relationship to Contraceptive Discontinuation: A Prospective Cohort Study in Pakistan and Uganda.

The quality of contraceptive counseling that women receive from their provider can influence their future contraceptive continuation. We examined (1) whether the quality of contraceptive service provision could be measured in a consistent way by using existing tools from 2 large-scale social franchises, and (2) whether facility quality measures based on these tools were consistently associated with contraceptive discontinuation. We linked existing, routinely collected facility audit data from social franchise clinics in Pakistan and Uganda with client data. Clients were women aged 15-49 who initiated a modern, reversible contraceptive method from a sampled clinic. Consented participants completed an exit interview and were contacted 3, 6, and 12 months later. We collapsed indicators into quality domains using theory-based categorization, created summative quality domain scores, and used Cox proportional hazards models to estimate the relationship between these quality domains and discontinuation while in need of contraception. The 12-month all-modern method discontinuation rate was 12.5% among the 813 enrolled women in Pakistan and 5.1% among the 1,185 women in Uganda. We did not observe similar associations between facility-level quality measures and discontinuation across these 2 settings. In Pakistan, an increase in the structural privacy domain was associated with a 60% lower risk of discontinuation, adjusting for age and baseline method (P<.001). In Uganda, an increase in the management support domain was associated with a 33% reduction in discontinuation risk, controlling for age and baseline method (P=.005). We were not able to leverage existing, widely used quality measurement tools to create quality domains that were consistently associated with discontinuation in 2 study settings. Given the importance of contraceptive service quality and recent advances in indicator standardization in other areas, we recommend further effort to harmonize and simplify measurement tools to measure and improve contraceptive quality of care for all.

Impact of adherence to National Comprehensive Cancer Network (NCCN)-recommended first-line therapy on treatment duration for patients with advanced non-squamous non-small cell lung cancer (NSCLC).

e21727 Background: Identification of molecular alterations can provide essential information to guide personalized treatment selection for advanced non-small cell lung cancer (aNSCLC) patients. However, in routine oncology practice, not all eligible patients receive biomarker testing and receive treatment according to the testing results following the National Comprehensive Cancer Network (NCCN) guideline. We aim to examine the impact of adherence to guideline-recommended therapy on the duration of treatment in a real-world setting. Methods: Patients diagnosed with non-squamous aNSCLC (stage IIIB and above) and received the first-line of therapy (FLOT) between 2011 and 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database were included in this analysis. Adherence was defined as using any NCCN guideline-recommended FLOT consistent with a patient’s biomarker testing results (EGFR, ALK, ROS1, BRAF and PD-L1) assessed up to 90 days before and/or 14 days after the FLOT start date. Non-adherence was defined as not receiving guideline-recommended FLOT based on the above-mentioned biomarker results, or patients treated without evidence of biomarker testing. Median time to treatment discontinuation (TTD) of FLOT was calculated using Kaplan-Meier analysis. Unadjusted and adjusted Cox proportional hazards regression models were used to evaluate the association between guideline adherence and TTD. Results: A total of 17,137 eligible patients were included (67.5% adherent, 32.5% non-adherent). Mean age at diagnosis was 67 years (SD: 10 years). The majority of patients (92%) received care at a community clinic, and 73% reported having insurance plans. Overall, 87.2% had discontinuation of FLOT, including 84.9% in the adherent group and 92.0% in the non-adherent group. The median TTD was 155 days (95% CI 153-159) in the adherent group and 128 days (95% CI 125-132) in the non-adherent group. Adherent patients had a lower risk of FLOT discontinuation in the unadjusted analysis (hazard ratio [HR] 0.78, 95% CI 0.76-0.81), which remained significant after adjusting for potential confounders including age at FLOT start, sex, history of smoking, and stage at initial diagnosis (HR 0.76, 95% CI 0.74-0.79). Conclusions: Among non-squamous aNSCLC patients, the majority of patients were adherent to NCCN guidelines. Adherence was associated with lower risk of discontinuation and longer duration of FLOT.

Real-world adherence and persistence for newly-prescribed HIV treatment: single versus multiple tablet regimen comparison among US medicaid beneficiaries

BackgroundOnce-daily, single-tablet regimens (STRs) have been associated with improved patient outcomes compared to multi-tablet regimens (MTRs). This study evaluated real world adherence and persistence of HIV antiretroviral therapy (ART), comparing STRs and MTRs.MethodsAdult Medicaid beneficiaries (aged ≥ 18 years) initiating ART with ≥ 2 ART claims during the identification period (January 1, 2015–December 31, 2016) and continuous health plan enrollment for a 12-month baseline period were included. For STRs, the first ART claim date was defined as the index date; for MTRs, the prescription fill claim date for the last drug in the regimen was defined as the index date, and prescription fills were required to occur within a 5-day window. Adherence was assessed in 30-day intervals over a 6-month period, with adherence defined as having less than a 5-day gap between fills. Persistence was evaluated as median number of days on therapy and percent persistence at 12 months. Cox Proportional Hazard models were used to evaluate risk of discontinuation, controlling for baseline and clinical characteristics.ResultsA total of 1,744 (STR = 1290; MTR = 454) and 2409 (STR = 1782; MTR = 627) patients newly prescribed ART had available data concerning adherence and persistence, respectively. Average age ranged 40–42 years. The patient population was predominantly male. Adherence assessments showed 22.7% of STR initiators were adherent to their index regimens over a 6-month period compared to 11.7% of MTR initiators. Unadjusted persistence analysis showed 36.3% of STR initiators discontinued first-line therapy compared to 48.8% for MTR initiators over the 2-year study period. Controlling for baseline demographic and clinical characteristics, MTR initiators had a higher risk of treatment discontinuation (hazard ratio [HR] = 1.6, p < 0.0001). Among STRs, compared to the referent elvitegravir(EVG)/cobicistat(COBI)/emtricitabine(FTC)/tenofovir alafenamide(TAF), risk of discontinuation was higher for efavirenz(EFV)/FTC/tenofovir disoproxil fumarate(TDF) (HR = 3.6, p < 0.0001), EVG/COBI/FTC/TDF (HR = 2.8, p < 0.0001), and abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) (HR = 1.8, p = 0.004). Among backbones, FTC/TAF was associated with lower risk of discontinuation than FTC/TDF (HR = 4.4, p < 0.0001) and ABC/3TC (HR = 2.2, p < 0.0001).ConclusionsAmong patients newly prescribed ART, STR initiators were significantly less likely to discontinue therapy and had greater adherence and persistence compared to MTR initiators. Regimens containing FTC/TAF as a backbone had higher persistence than those consisting of other backbones.

Comparison of Real-World Treatment Patterns Among Psoriasis Patients Treated with Ixekizumab or Adalimumab.

BackgroundThere is lack of real-world treatment pattern comparison data between ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis.ObjectiveTo compare real-world treatment patterns among psoriasis patients initiating ixekizumab or adalimumab in the United States.MethodsPsoriasis patients with ≥1 claim for ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan® databases. Patients were required to be continuously enrolled for ≥12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence.ResultsA total of 646 ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69–0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62–0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57–0.91). Ixekizumab users had higher odds of medication possession ratio ≥80% (odds ratio [OR]=1.36, 95% CI: 1.10–1.69) but similar odds by proportion of days covered ≥80% (OR=1.22, 95% CI: 0.98–1.53).ConclusionPsoriasis patients treated with ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥80%, it did not by PDC ≥80%; hence, further analysis using fixed-length follow-up is required.