Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

BACKGROUND: The first-generation BTK inhibitor ibrutinib is a standard-of-care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. METHODS: This study used 2013-2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. RESULTS: The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow-up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient-months for all discontinuers and 32.9 per 1000 patient-months for non-discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient-months compared with non-discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). CONCLUSION: In this first real-world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib-related AEs and/or new treatments to improve real-world outcomes in patients with CLL.

Real-world adherence and discontinuation among Medicare beneficiaries initiating venetoclax vs. BTKis in relapsed/refractory chronic lymphocytic leukemia.

The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015-2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.

Impact of Updated Clinical Practice Guidelines on Outpatient Treatment for Clostridioides difficile Infection and Associated Clinical Outcomes.

Background: The 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) Clostridium (Clostridioides) difficile infection (CDI) guideline update recommended treatment with fidaxomicin or vancomycin for CDI. We aimed to examine outpatient CDI treatment utilization before and after the guideline update and compare clinical outcomes associated with fidaxomicin versus vancomycin use. Methods: A pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April-September 2017 (preguideline period) and those indexed from April-September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score-matched analyses. Results: From the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all). However, clinical outcomes did not improve. In propensity score-matched analyses, fidaxomicin versus vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% confidence interval [CI], 4.0%-22.9%; P = .0058) and 30.0% (95% CI, 16.8%-44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts. Conclusions: Vancomycin use increased and metronidazole use decreased after the 2017 guideline update. Fidaxomicin use increased but remained low. Improved outcomes associated with fidaxomicin relative to vancomycin suggest benefits from its greater use in Medicare patients.

Barriers and solutions to improve access for chimeric antigen receptor therapies.

Chimeric antigen receptor T cells are a potentially curative new therapeutic option, but access challenges remain. The limited number of certified treatment centers and the need to travel to these centers, the expenses of travel and lodging and the out-of-pocket costs associated with treatment pose a challenge for patients. Further, the logistics of follow-up coupled with an ad hoc reimbursement environment make chimeric antigen receptor T-cell treatment an unattractive proposition for many providers. The patient-specific nature of these gene therapies has made scaling up production difficult for manufacturers. Providing expanded financial assistance for patients and education for community oncologists, and addressing reimbursement challenges, can alleviate some of these access barriers.

Chimeric antigen receptor T cells are a new type of cancer treatment where the cells from a patient's own blood are changed in the laboratory and injected back into the patient so they attack cancer cells. While these drugs offer a possible cure for some cancers, patients have had problems getting these treatments because there are not many approved treatment centers. Patients have to travel to these centers, and there can be high out-of-pocket costs for travel, a place to stay and the treatment itself. The paper discusses several ways to make it easier to get these treatments, such as helping patients pay for lodging and travel and changing insurance payment policies for chimeric antigen receptor T cell treatment.

Treatment utilization patterns of newly initiated oral anticancer agents in a national sample of Medicare beneficiaries.

BACKGROUND: Few studies have examined oral anticancer treatment utilization patterns among Medicare beneficiaries. OBJECTIVE: To assess treatment utilization patterns of newly initiated oral anticancer agents across national samples of Medicare beneficiaries for 5 cancer types: chronic myeloid leukemia (CML), multiple myeloma (MM), metastatic prostate cancer (mPC), metastatic renal cell carcinoma (mRCC), and metastatic breast cancer (mBC). METHODS: This retrospective claims analysis used 100% Medicare Chronic Condition Data Warehouse (CCW) Parts A, B, and D files from 2011 to 2014 (for CML, MM, mPC, and mRCC patients) and a 5% random fee-for-service sample from 2011 to 2013 (for mBC patients). Outcomes of interest were the number of 30-day supply prescriptions, adherence, and discontinuation of newly initiated (ie, index) oral anticancer agents indicated for each of the cancers. Adherence was calculated with both the "traditional" proportion of days covered (PDC) approach, measured over a fixed 1-year period or until hospice/death, and a "modified" PDC approach, measured over the time between the first and last fill of the index oral anticancer agent. Patients with PDC of at least 0.80 were deemed as being adherent. Discontinuation was defined as the presence of a continuous 90-day gap in the availability of days supply of the index oral anticancer agent. RESULTS: Our study included 1,650, 7,461, 6,998, 2,553, and 79 patients for CML, MM, mPC, mRCC, and mBC, respectively. Patients with mRCC had the highest proportion of patients with only 1 fill of their index anticancer agent (28%) followed by mBC (17%), MM (17%), mPC (12%), and CML (12%). Patients with CML had the highest mean (SD) number of 30-day supply equivalent prescriptions (8.3 [4.6]), followed by patients with mPC (6.5 [4.2]), MM (5.7 [4.1]), mBC (4.7 [3.2]), and mRCC (4.5 [3.9]). Using the modified PDC measured between the first and last fills, approximately three-quarters of patients with CML (74%), mRCC (71%), and mBC (70%) were adherent to the index oral anticancer agent. Adherence was highest for patients with mPC (87%) and lowest for patients with MM (58%). The percentage of patients defined as adherent to the index oral anticancer agent decreased for all cancers when using the traditional PDC measure over a fixed 1-year period: CML (54%), MM (35%), mPC (48%), mRCC (37%), and mBC (22%). Rates of discontinuation for patients in our sample were 32% (CML), 38% (mPC), 42% (mRCC), 48% (MM), and 58% (mBC). CONCLUSIONS: Between 13% and 42% of Medicare patients were nonadherent between the first and last fill of their newly initiated oral anticancer therapies across a range of cancers. This study provides a valuable benchmark for stakeholders seeking to measure and improve adherence to oral anticancer agents in Medicare patients. DISCLOSURES: This study was supported by Humana, Inc. (Louisville, KY). The sponsor played a role in the development of the study protocol, interpretation of results, and revisions of the manuscript. The sponsor was not involved in data analysis. Brown is employed by Humana, Inc., and Ward was employed by Humana, Inc., from research inception through initial drafts. Doshi has served as an advisory board member or consultant for Allergan, Ironwood Pharmaceuticals, Janssen, Kite Pharma, Merck, Otsuka, Regeneron, Sarepta, Sage Therapeutics, Sanofi, and Vertex and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, PhRMA, Regeneron, Sanofi, and Valeant. Her spouse holds stock in Merck and Pfizer. All other authors have no financial conflicts of interest to report.

Trends and Factors Associated With Insurer Approval of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Prescriptions.

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is)-innovative yet costly cholesterol-lowering agents-have been subject to substantial prior authorization (PA) requirements and low approval rates. We aimed to investigate trends in insurer approval and reasons for rejection for PCSK9i prescriptions as well as associations between patients' demographic, clinical, pharmacy, payer, and PCSK9i-specific plan/coverage factors and approval. METHODS: We examined trends in PCSK9i approval rates and reasons for rejection using medical and prescription claims from 2015 to 2017 for individuals who received a PCSK9i prescription. We used multinomial logistic regression to estimate quarterly risk-adjusted approval rates for initial PCSK9i prescriptions and approval for any PCSK9i prescription within 30, 90, and 180 days of the initial PCSK9i prescription. For a 2016 subsample for whom we had PCSK9i-specific plan policy data, we examined factors associated with approval including PCSK9i-specific plan formulary coverage, step therapy requirements, and number of PA criteria. RESULTS: The main sample included 12 309 patients (mean age 64.8 years [SD = 10.8], 52.1% female, 51.5% receiving Medicare) and was similar in characteristics to the 2016 subsample (n = 6091). Approval rates varied across quarters but remained low (initial prescription, 13%-23%; within 90 days, 28%-44%). Over time, rejections owing to a lack of formulary coverage decreased and rejections owing to PA requirements increased. Lack of formulary coverage and having ≥11 PA criteria in the plan policy were associated with lower odds of PCSK9i prescription approval. CONCLUSIONS: These findings confirm ongoing PCSK9i access issues and offer a baseline for comparison in future studies examining the impact of recent efforts to improve PCSK9i access.

Omalizumab Treatment Patterns Among Patients with Asthma in the US Medicare Population.

BACKGROUND: Asthma in older adults is associated with high rates of morbidity and mortality; similarly, asthma can be severe enough among younger adults to warrant disability benefits. Reasons for poor outcomes in both groups of patients may include discontinuation and lack of adherence to controller therapies. OBJECTIVE: To examine characteristics and treatment patterns of US Medicare patients initiating omalizumab for asthma, and factors associated with its discontinuation and adherence. METHODS: A retrospective claims database analysis of Medicare beneficiaries with asthma initiating omalizumab treatment was carried out. The primary outcomes were omalizumab discontinuation (gap in use ≥90 days) and adherence (proportion of days covered ≥0.8) over a 12-month follow-up. Multivariable regressions were used to examine factors associated with omalizumab discontinuation and adherence. RESULTS: Of the 3058 Medicare patients initiating omalizumab for asthma (mean age, 62.7 years), 36.9% discontinued omalizumab and 60.6% were adherent. Discontinuation rates were 32.7% and 42.8%, and adherence rates were 65.4% and 53.9%, for disabled and older Medicare patients, respectively. Patients aged 65 to 69 years and 70 to 74 years had significantly lower odds of discontinuation (odds ratios [95% CI], 0.66 [0.46-0.93] and 0.62 [0.43-0.89], respectively) and higher odds of adherence than did patients aged 80 years or older. Compared with patients receiving low-income subsidy, patients not receiving low-income subsidy had lower odds of discontinuation (0.66 [0.52-0.83]) and higher odds of adherence (1.52 [1.20-1.93]). Greater numbers of preindex evaluation and management physician visits and comorbid rhinitis were associated with lower odds of discontinuation and higher odds of adherence. CONCLUSIONS: More than 60% of Medicare patients with asthma continued and were adherent to omalizumab over a 12-month follow-up. Patient age, low-income subsidy status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation.

Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol. However, the high costs of these agents have spurred payers to implement utilization management policies to ensure appropriate use. We examined prior authorization (PA) requirements for PCSK9is across private and public US payers. METHODS AND RESULTS: We conducted an analysis of 2016 formulary coverage and PA data from a large, proprietary database with information on policies governing >95% of Americans with prescription drug coverage (275.3 million lives) within 3872 plans across the 4 major insurance segments (commercial, health insurance exchange, Medicare, and Medicaid). The key measures included administrative PA criteria (prescriber specialty, number of criteria in PA policy or number of fields on PA form, requirements for medical record submission, reauthorization requirements) and clinical/diagnostic PA criteria (approved conditions, required laboratories or other tests, required concomitant therapy, step therapy requirements, continuation criteria) for each of 2 Food and Drug Administration-approved PCSK9is. Select measures (eg, number of PA criteria/fields, medical record submission requirements) were obtained for 2 comparator cardiometabolic drugs (ezetimibe and liraglutide). Between 82% and 97% of individuals were enrolled in plans implementing PA for PCSK9is (depending on insurance segment), and one third to two thirds of these enrollees faced PAs restricting PCSK9i prescribing to a specialist. For patients with familial hypercholesterolemia, diagnostic confirmation via genetic testing or meeting minimum clinical scores/criteria was also required. PA requirements were more extensive for PCSK9is as compared with the other cardiometabolic drugs (ie, contained 3×-11× the number of PA criteria or fields on PA forms and more frequently involved the submission of medical records as supporting documentation). CONCLUSIONS: PA requirements for PCSK9is are greater than for selected other drugs within the cardiometabolic disease area, raising concerns about whether payer policies to discourage inappropriate use may also be restricting access to these drugs in patients who need them.