Initial monotherapy for Parkinson’s disease (PD) includes carbidopa/levodopa; however, treatment approaches vary with disease progression owing to fluctuations in symptom control and increasing disability. This study describes treatment patterns in newly treated patients with PD following carbidopa/levodopa initiation. This retrospective study analyzed claims from a large insurance database. Patients with PD (≥1 inpatient or ≥2 outpatient claims with International Classification of Diseases, Ninth Revision, Clinical Modification [332.xx] or Tenth Revision, Clinical Modification [G20.xx, G21xx] codes) were identified. Among these patients, the index date was the date of the first observed claim for oral carbidopa/levodopa medication from 1/1/2016 to 12/31/2019. Patients were lacking carbidopa/levodopa claims during the 1-year preindex period (baseline) and continuously enrolled during baseline and ≥1 year post index (follow-up). Treatment patterns of various PD medications following initiation of carbidopa/levodopa were measured during follow-up. We identified 16,531 carbidopa/levodopa treatment-naïve patients. Mean (SD) age was 75.3 (8.4) years, 40.5% were female, and 66.2% were White. Mean (SD) number of chronic conditions was 6.0 (2.4). Mean (SD) time from first observed PD diagnosis to the index treatment was 124.5 (153.2) days. Most commonly used index carbidopa/levodopa formulation was the 25/100-mg tablet (81.7%). Median index treatment duration was 238 days; 76.5% of patients discontinued index treatment (ie, had a gap in index treatment of ≥30 days) by follow-up end. During the follow-up period, 31.4% (n=5187) of patients used concomitant PD medication (median 90 days until start), with dopamine agonists being most common (19.7%). Among 5187 patients, 23.9% switched to/added a second class of concomitant medication (median 133 days until event), with dopamine agonist add-on combinations (with monoamine oxidase type B inhibitors or amantadine) being most frequent (49.6%). Treatment patterns suggest that even with medications concomitant to oral carbidopa/levodopa, a need exists for additional therapies to control motor symptoms.

To study associations between initiating eslicarbazepine acetate (ESL) vs. brivaracetam (BRV) after switching from generic antiseizure drugs (ASDs) and healthcare resource utilization (HCRU) and charges among patients with treated focal seizures (FS). This retrospective longitudinal cohort analysis used Symphony Health's Integrated Dataverse claims during 4/1/2015−6/30/2018, with separate cohorts for switches to ESL and BRV following 1 generic ASD. Index date was the earliest claim for ESL or BRV. Patients had 1 generic ASD in the 12 months before index date, ≥1 medical claim with a FS diagnosis, and were ≥ 4 years old. Unit of analysis was the 90-day person-time-block. Baseline period was the block preceding index date, and patients had up to four blocks following. Inverse probability treatment weighted linear regression models with person fixed effects assessed pre-post and between-cohort changes in all-cause and FS-related HCRU and charges. 282 patients initiated ESL (45.1 years, 57.5% female) and 139 BRV (42.7 years, 61.9% female). Levetiracetam was the most common prior ASD (ESL:44.3%, BRV:54.7%). Compared to baseline, ESL patients had reductions in all-cause (7.8 percentage point reduction (ppr); p=0.001) and FS-related (3.4 ppr; p = 0.017) inpatient hospitalization. Both cohorts experienced significant reductions in all-cause and FS-related outpatient visits. Compared to BRV, ESL patients had larger reductions in all-cause outpatient visits (9.0 ppr; p=0.008). Compared to baseline, ESL patients had reductions in all-cause (-$3,017; p<0.001) and FS-related (-$1,016; p=0.002) medical charges, non-FS related medical charges (-$2,001; p=0.001), and all-cause (-$1,544; p=0.013) and FS-related (-$851; p =0.004) outpatient charges. Compared to BRV patients, ESL patients had larger numerical reductions in all categories of all-cause and FS-related charges considered, except FS-related outpatient charges. FS patients switching to ESL (vs.BRV) after one generic ASD had larger reductions in all-cause and FS-related HCRU and charges, except FS-related outpatient HCRU and charges.

Background: "On-demand" treatments approved in the United States (US) for "OFF" episodes in Parkinson's disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing "OFF" episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments' pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without "OFF" episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per "OFF" hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total "on-demand" treatment costs ($42,095) compared with SC-APO ($276,320; difference: -$234,225) and CVT-301 ($69,577; difference: -$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per "OFF" hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and adverse event-related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of "OFF" episodes in patients with PD.

To conduct an indirect treatment comparison (ITC) of 2 approved routes of apomorphine administration for the on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD): apomorphine sublingual film (APL-130277; APL) and apomorphine subcutaneous injection (apo-SC). A systematic literature review was conducted and updated until 20May2020 to identify relevant randomized controlled trials. Eight studies were identified, which varied in design (eg, duration, placebo arm, assessment methods, etc). Outcomes included: (1) change from baseline in Part III score of Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) for APL or UPDRS for apo-SC, (2) mean reduction in “OFF” time (determined by patient-reported “OFF”/FULL “ON” status at discrete timepoints between 0–90 minutes for APL or by mean number of treated “OFF” episodes/day multiplied by mean reduction in “OFF” time/episode due to therapy as reported in patient diaries for apo-SC), and (3) the proportion of patients who turned FULLY “ON” (for APL) or “ON” (for apo-SC) based on patient diaries. ITC feasibility was assessed based on data availability and heterogeneity across studies. Apo-SC had a more favorable mean change in UPDRS Part III score at 20 minutes postdose vs APL in MDS-UPDRS Part III score at 30 minutes postdose (mean difference [95% credible interval], –12.4 [–17.2, –7.6]), APL and apo-SC had similar response estimates at 60 minutes postdose (–0.5 [–8.0, 7.0]), and APL had a more favorable response estimate vs apo-SC at 90 minutes postdose (–8.2 [–15.0, –1.4]). APL and apo-SC had a similar estimated mean reduction in “OFF” time (mean difference [95% credible interval], 4.38 minutes [–7.5, 16.2]). Data limitations prevented ITCs for the proportion of patients who turned FULLY “ON”/“ON.” ITCs suggest that APL may provide comparable efficacy to apo-SC, therefore other factors, such as route of administration, may influence specific treatment decisions.

Patients with Parkinson's disease (PD) treated with levodopa often develop "OFF" episodes, which are characterized by the reappearance or worsening of motor and/or non-motor symptoms. "OFF" episodes may lead to a patient's loss of independence in basic day-to-day functioning and the need for increased caregiver aid. This study aimed to understand the association between "OFF" hours and caregiver burden. We analyzed data collected between 2017-2019 from the Adelphi Parkinson's Disease Specific Programme, a cross-sectional, observational US study of neurologists, their consulting patients with PD, and the patients' caregivers. "OFF" hours were physician-reported, and caregiver burden was self-reported using the 22-item Zarit Burden Interview (ZBI; range score, 0-88). Eligible patients were those who were prescribed levodopa at the time of data capture, and whose respective caregivers had voluntarily completed a caregiver self-completion form. Multiple linear regression analysis was used to determine the association between the number of daily "OFF" hours (compared continuously from zero upwards) and caregiver burden. Regressions were adjusted for patient age, sex, body mass index, comorbidities, and current disease severity as determined by the Hoehn and Yahr scale. Data were available for 235 patients who had a physician-completed patient record form and corresponding caregiver self-completion form. Patients experienced a mean (standard deviation) daily "OFF" time of 1.67 (1.85) hours. Increased daily "OFF" hours were significantly associated with increased caregiver burden for the overall ZBI score (+1.62; P=0.001) and several of its domains: personal strain (+0.91; P=0.003), role strain (+0.98; P<0.001), relationship burden (+0.42; P=0.003), emotional well-being (+0.53; P=0.001), finances (+0.13; P=0.002), and loss of control over one's life (+0.27; P=0.014). Increased "OFF" hours among patients with PD were associated with an increased degree of burden for their caregivers, as measured by the ZBI, highlighting the importance of optimal clinical management of "OFF" episodes.

Quantify patient preferences for on-demand treatments for Parkinson’s disease (PD)-related “OFF” episodes (ie, symptom reappearance/worsening). US adults (18–75 years) with self-reported PD for ≥5 years or <5 years with “OFF” episodes on levodopa were recruited for an online discrete-choice experiment survey. Respondents selected between pairs of experimentally designed profiles for hypothetical on-demand “OFF” treatments that varied by mode of administration (with and without mode-specific adverse events [AEs]), time to FULL “ON,” duration of “ON,” and out-of-pocket cost for 30 doses. Data were analyzed by random-parameters logit model and results used to calculate relative importance of treatment attributes and willingness to pay (WTP). Among 300 respondents, 98% had “OFF” episodes. Over the attribute levels presented, increasing duration of “ON” from 1 to 2 hours was least important. Avoiding $90 cost was most important (9.7 times as important as duration of “ON”) followed by change in mode from injection with site reactions to dissolvable sublingual film without AEs (8.9 times as important as duration of “ON”) and decreasing time to “ON” from 60 to 15 minutes (6.2 times as important as duration of “ON”). Given a choice of mode, dissolvable sublingual film with potential mouth sores was preferred vs inhalation with potential cough or mild respiratory infection (2.2 times as important) or injection with potential site reactions (4.7 times as important). Average WTP to move from injection with site reactions (least preferred) to dissolvable sublingual film without AEs (most preferred) was $83 and was $58 to decrease time to FULL “ON” from 60 to 15 minutes. Based on attributes and levels presented, patients with PD placed most importance on avoidance of high out-of-pocket cost and mode of administration when choosing an on-demand treatment for “OFF” episodes. Time to FULL “ON” was also an important driver of choice.

Background: Better understanding of migraine treatment in US clinical practice could be facilitated by availability of Migraine Disability Assessment (MIDAS) questionnaire results collected in routine care. We present results for migraine patients with MIDAS collected in routine clinical practice through an electronic medical record (EMR) system that presented the MIDAS questionnaire as an electronic form during the patient office encounter. The purpose of this retrospective observational study was to gain better understanding of migraine disability and migraine treatment patterns in US real-world clinical practice. Methods: In this EMR database study, patients were required to have 12 months baseline time for review of patient and clinical characteristics. Adult patients with documentation of migraine with subsequent MIDAS questionnaire data collected between March 2017 and September 2018 were included. Based on MIDAS responses patients were categorized into grade I—little or no disability, grade II—mild disability, grade III—moderate disability, and grade IV—severe disability. Results: This study included 2731 migraine patients with MIDAS results. Overall, 2309 (84.5%) were female with an average age of 46.7 years. Distribution by disability grade was 1161 (42.5%) little or no disability, 424 (15.5%) mild disability, 477 (17.5%) moderate disability, and 669 (24.5%) severe disability. Compared to overall, a larger proportion of patients with severe disability had baseline treatment with acute (71.3% vs. 67.6%) or preventive medications (70.4% vs. 62.0%) and to be on 3+ acute (9.4% vs. 7.0%) or 3+ preventive therapies (17.0% vs. 14.5%). Conclusion: Availability of MIDAS results in usual care provides additional insight into migraine care.

Little is known about factors influencing patients' OFF-episode treatment preference in Parkinson's disease (PD). Fit-for-purpose preference questionnaires are lacking in the evaluation of PD treatments. The Treatment Preference Questionnaire (TPQ) was developed to explore patients' experience with and preference for OFF-episode treatment and further evaluate clinical benefits of APL-130277, a sublingual formulation of apomorphine, shown in a pivotal trial (CTH-300; NCT02469090) to be effective and generally well tolerated in treating OFF-episodes in PD patients. This study confirmed the content validity of the TPQ. Three rounds of qualitative interviews were conducted with adults with PD and OFF-episodes, according to a semi-structured interview guide. Rounds 1 and 2 included concept elicitation and debriefing of the 9-item TPQ; Round 3 included debriefing only. Twenty-six interviews were conducted with 22 adults (4 participated in both Rounds 2 and 3). All participants reported OFF-episodes and current Levodopa/carbidopa use; mean time since diagnosis was 10.4 years. Rapid onset (73%), efficacy (reduced/alleviated symptoms; 59%), lack of side effects (45%), and mode of administration and portability (32%) were most commonly included in participants' list of top 3 treatment attributes influencing preference. During debriefing, all participants reported that the TPQ assessed concepts most relevant to determining preference for an OFF-episode medication (specifically ease of use, efficacy, speed of onset, durability, and side effects). Illustrative quotes include: "I'm thinking about feeling better, quicker, longer, being more normal." "I can't think of anything else you'd want to put in there." Only treatment cost was noted as missing. All participants reported most items were clear and easy to understand and answer. One item was revised during this process and successfully debriefed in Rounds 2 and 3. These data support the salience of TPQ concepts, the ease with which patients understood and answered the TPQ, and overall content validity.

Patients with Parkinson’s disease (PD) experience an onset of motor and/or non-motor symptoms (MS; NMS), including slowed movement, resting tremor, gait and balance problems; anxiety, depression and cognitive impairment. The economic burden associated with PD is considerable, but little is known about the cost engendered by the presence of NMS, which are often treated as peripheral issues to MS. We evaluated healthcare resource utilization (HRU) among real-world PD patients with motor-only (MO) and motor plus non-motor (MNM) symptoms. Data analysed were captured in the 2017 Adelphi Parkinson’s Disease Specific Programme, a point-in-time observational study of 109 neurologists and their consulting PD patients of all disease stages in the US. Patients were separated into two groups for analysis: MO patients and MNM patients, then propensity-score matched for age, sex, BMI, quantities of both motor and non-motor comorbidities and current Hoehn & Yahr severity. The groups were then compared for differences in HRU costs arising from physician-recorded consultations, hospitalisations and treatment related to PD in the last 12 months. From a population of 1,409 PD patients, physician-reported data for 383 MO and 1,019 MNM entered the propensity-score matching analysis. Over the 12 months preceding the most recent consultation, the mean PD-related HRU costs (US Dollars) per patient were: consultations with healthcare professionals totalling $236 for MO vs. $370 for MNM (p<0.001); hospitalisations totalling $245 for MO vs. $1,246 for MNM (p<0.001); and prescribed treatment totalling $1,256 for MO vs. $2,314 for MNM patients (p<0.001). Parkinson’s disease patients with non-motor symptoms alongside motor symptoms had a significantly higher annual PD-related cost - in terms of consultations with healthcare professionals, hospitalisations and prescribed treatment - than those with motor-only symptoms. Further research is required into the presence of non-motor symptoms in order to quantify their burden and the benefits of their treatment.

BACKGROUND:Adherence to disease-modifying therapy (DMT) remains problematic for many patients with multiple sclerosis (MS). An improved understanding of factors affecting DMT adherence may inform effective interventions. This study examined associations between treatment satisfaction, medication beliefs, and DMT adherence. METHODS:A survey was mailed in 2016 to 600 adult patients with relapsing-remitting MS taking an injectable or oral DMT. Patients were sampled from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. The survey measured self-reported DMT adherence (doses taken divided by doses prescribed during previous 2-week period-adherence ≥0.80), DMT satisfaction using the Treatment Satisfaction Questionnaire for Medication version II, medication beliefs using the Beliefs About Medicines Questionnaire, and demographic and clinical covariates. Relationships between variables were examined using multivariate logistic regression. RESULTS:Final analyses included 489 usable surveys. Mean ± SD participant age was 60.5 ± 8.3 years. Most respondents were white (93.8%), female (86.6%), taking an injectable DMT (66.9%), and adherent to DMT (92.8%). Significant predictors of DMT adherence were age (odds ratio [OR], 1.086; 95% CI, 1.020-1.158; P = .011), type of DMT (oral vs. injectable; OR, 23.350; 95% CI, 2.254-241.892; P = .008), and DMT experience (naive vs. experienced; OR, 2.831; 95% CI, 1.018-7.878; P = .046). CONCLUSIONS:In patients with MS sampled from a patient registry, treatment satisfaction and medication beliefs were not significantly associated with DMT adherence. Based on significant predictors, younger patients, patients taking injectable DMTs, and patients with previous experience with another DMT(s) are at higher risk for nonadherence. Future research is warranted to assess relationships between variables in more diverse MS populations.

To describe opioid and other acute medication use in patients presenting to the emergency department (ED) with migraine. This was a retrospective analysis using electronic medical records (EMRs) from Ochsner Health System, Louisiana from 2011 to 2016. Records were extracted for patients aged >18 with an ED visit coded for migraine and with at least six months baseline data. Descriptive statistics of patient demographics and acute medication use during the ED visit were summarized. Across 5,948 patients that met inclusion and exclusion criteria during the study period, a total of 15,153 unique ED encounters with a code for migraine were extracted. At least one acute prescription medication was administered in 9,204 (60.7%) of these encounters. Among ED visits for migraine where prescription medication was administered, nearly half (n=4,370/9,204, 47.5%) included at least one opioid. IV hydromorphone was administered in more than half (n=2,473/4,370, 56.6%) of these ED visits. In over one-fourth (n=1,144/4,370, 26.2%) of ED encounters in which an opioid was administered, patients were administered more than one dose of an opioid (i.e., either administration of a different opioid or administration of the same opioid with same or increased dose). Among non-opioid medications (e.g., antiemetics and non-opioid analgesics), antiemetics were the most frequently administered class, given in over one-third of ED (n=3,617/9,204, 39.3%) encounters where acute prescription medication was administered. Despite best practice guidelines discouraging the use of opioids for migraine, opioids were administered in nearly half of the ED visits, pointing to potentially suboptimal care. Future research focusing on elucidating factors related to clinical decision making in the management of migraine in the ED and barriers to the utilization of effective preventive therapies is needed to reduce opioid overutilization.

Optimal adherence to disease modifying therapies (DMTs) is important to maximize clinical benefits among multiple sclerosis (MS) patients. Poor adherence to DMT can lead to relapse or progression of MS, which worsens patient outcomes. This research aims to qualitatively explore patients’ experiences with DMTs to better understand complex and multifactorial causes of decreased adherence among MS patients. Patients aged 18 years or older, diagnosed with relapsing MS, and prescribed an injectable and/or oral DMT were eligible to participate in the focus groups. Three separate focus groups, based on currently prescribed DMT (injectable, oral, and mix of injectable or oral), were conducted in Austin, TX. Three main areas of discussion were: medication burden, barriers of adherence, and coping strategies. An inductive content analysis was used to identify emergent themes from the data. Twenty-six MS patients were assigned to one of three focus groups: injectable (n=10), oral (n=6), or mix of injectable and oral (n=10). Majority were female (65.4%) and Caucasian (73.1%). On average, patients were 49.6±9.2 years old and had MS for 12.3±6.6 years. Four major themes emerged: DMT-related issues, barriers of adherence, facilitators of adherence (currently used), and facilitators of adherence (desired). DMT-related issues (e.g., administration, storage) contributed to overall medication burden for patients rather than directly impacting adherence; however, several barriers and facilitators (e.g., memory, lack of motivation) directly impacted adherence. Patients utilized various strategies, such as industry-sponsored support programs and reminder devices, to improve adherence and expressed their desire for easier DMT administration and ordering processes. This study identified multiple DMT-related issues, barriers of DMT adherence, and various methods and strategies employed by patients to improve adherence. Findings from this study may be used to tailor initiatives aimed at improving adherence, which may help patients realize full clinical benefits of DMT.