Using observational analysis of multiple sclerosis relapse to design outcomes-based contracts for disease-modifying drugs: a feasibility assessment

Abstract

Objective:

To assess predictors and costs of multiple sclerosis (MS) relapse, a potential outcome measure in payer-manufacturer risk-sharing agreements for disease-modifying drugs (DMDs).

Methods:

A retrospective cohort analysis of medical/pharmacy claims was used. Study patients had ≥1 DMD (interferon beta, glatiramer, natalizumab) claim, without DMD claims in a 6-month pre-period before DMD initiation; were aged 18–64 years and continuously enrolled from the pre-period through a 24-month post-period; and had ≥2 MS medical claims during the 30-month study period. Post-period relapse cohorts included: (1) severe (hospitalization with MS diagnosis); (2) moderate (outpatient services including intravenous methylprednisolone); and (3) none. Poisson regression modeled severe relapse frequency, logistic regression modeled ≥1 severe relapse, and generalized linear modeling predicted healthcare costs. Tested predictors included demographics, insurance type, index DMD, pre-period health status, and DMD medication possession ratio (MPR).

Results:

Severe relapse was experienced by 14.5% and moderate relapse by 13.8% of 2291 patients. In logistic regression, severe relapse was predicted by plan type; age (odds ratio [OR]?=?1.018, 95% confidence interval [CI]?=?1.005–1.031); pre-period Charlson Comorbidity Index (OR?=?1.307, 95% CI?=?1.166–1.464); pre-period proxy measure indicating impaired activities of daily living (OR?=?1.470, 95% CI?=?1.134–1.905); pre-period MS hospitalization (OR?=?2.174, 95% CI?=?1.537–3.074); and DMD non-adherence (MPR OR?=?0.101, 95% CI?=?0.068–0.151). Poisson regression results were similar. Predicted mean [standard deviation] all-cause healthcare expenditures were tripled for patients with severe compared with moderate relapse ($48,173 [$8665] and $13,334 [$1929], respectively).

Limitations:

Commercially insured patients from a single payer; use may have been inconsistent with approved indications; proxy relapse measure may have misclassified patients.

Conclusions:

Severe MS relapses requiring hospitalization, although affecting less than 15% of patients initiating DMD treatment, are associated with high medical costs. The only actionable predictor of severe relapse identified in observational analysis was MPR, raising questions about the feasibility of using observational data to guide outcomes-based contracting.     

Adherence to iron chelation therapy and associated healthcare resource utilization and costs in Medicaid patients with sickle cell disease and thalassemia

Background:

Sub-optimal patient adherence to iron chelation therapy (ICT) may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with sickle cell disease (SCD) or thalassemia.

Methods:

Patients with SCD or thalassemia were identified from six state Medicaid programs (1997–2013). Adherence was estimated using the medication possession ratio (MPR) of ≥0.80. All-cause and disease-specific resource utilization per-patient-per-month (PPPM) was assessed and compared between adherent and non-adherent patients using adjusted incidence rate ratios (aIRR). All-cause and disease-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to compare adherent and non-adherent patients.

Results:

A total of 728 eligible patients treated with ICT in the SCD cohort, 461 (63%) adherent, and 218 in the thalassemia cohort, 137 (63%) adherent, were included in this study. In SCD patients, the adjusted rate of all-cause outpatient visits PPPM was higher in adherent patients vs non-adherent patients (aIRR [95% CI]: 1.05 [1.01–1.08], p?<?0.0001). Conversely, adherent patients incurred fewer all-cause inpatients visits (0.87 [0.81–0.94], p?<?0.001) and ER visits (0.86 [0.78–0.93], p?<?0.001). Similar trends were observed in SCD-related resource utilization rates and in thalassemia patients. Total all-cause costs were similar between adherent and non-adherent patients, but inpatient costs (adjusted cost difference?=??$1530 PPPM, p?=?0.0360) were lower in adherent patients.

Conclusion:

Patients adherent to ICT had less acute care need and lower inpatient costs than non-adherent patients, although they had more outpatient visits. Improved adherence may be linked to better disease monitoring and has the potential to avoid important downstream costs associated with acute care visits and reduce the financial burden on health programs and managed care plans treating SCD and thalassemia patients.     

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts

Abstract

Objective:

To study outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (Copaxone) or interferon beta-1a for once-weekly, intramuscular administration (Avonex).

Methods:

An ‘intent-to-treat’ (ITT) cohort (n?=?1282) was established, consisting of patients diagnosed with MS who began therapy on either glatiramer acetate (GA) or intramuscular interferon beta-1a (IFN beta-1a-IM) and had continuous insurance coverage from 6 months before to 24 months after the date when they began taking the medication. A ‘persistent use’ (PU) cohort (n?=?639) was also constructed, consisting of individuals who, in addition to the criteria listed above, had a claim for GA or IFN beta-1a-IM within 28 days of the end of the 2-year post-period. Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. Multivariate regressions were used to examine both the 2-year total direct medical costs and the likelihood of relapse associated with the use of each of these alternative MS medications. A relapse was defined as either being hospitalized with a principal diagnosis of MS or having an outpatient visit with a MS diagnosis followed within 7 days by a claim for a corticosteroid. All regressions controlled a wide range of factors that may potentially affect outcomes.

Results:

In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (10.01 vs. 5.18%; p?=?0.0034) as well as significantly lower 2-year total medical costs ($44,201 vs. $41,121; p?=?0.0294). In the PU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (7.25 vs. 2.16%; p?=?0.0048) as well as significantly lower total medical costs ($67,744 vs. 63,714; p?=?0.0445).

Limitations:

The analyses relies on an administrative claims database of an insured population and hence, may not be generalizeable to other populations. In addition, such a database precludes measurement of lost work time, unemployment, caregiver burden or other costs associated with MS.

Conclusions:

Results from this study indicate that the use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs than IFN beta-1a-IM.     

Real-world treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriasis

Objective: This study compared real-world treatment patterns and healthcare costs among biologic-naive psoriasis patients initiating apremilast or biologics.

Methods: A retrospective cohort study was conducted using the Optum Clinformatics? claims database. Patients with psoriasis were selected if they had initiated apremilast or biologics between January 1, 2014, and December 31, 2015; had 12?months of pre-index and post-index continuous enrollment in the database; and were biologic-naive. The index date was defined as the date of the first claim for apremilast or biologic, and occurred between January 1, 2014, and December 31, 2015. Treatment persistence was defined as continuous treatment without a?>?60-day gap in therapy (discontinuation) or a switch to a different psoriasis treatment during the 12-month post-index period. Adherence was defined as a medication possession ratio (MPR) of ≥ 80% while persistent on the index treatment. Persistence-based MPR was defined as the number of days with the medication on hand measured during the patients’ period of treatment persistence divided by the duration of the period of treatment persistence. Because patients were not randomized, apremilast patients were propensity score matched up to 1:2 to biologic patients to adjust for possible selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.

Results: In all, 343 biologic-naive patients initiating apremilast were matched to 680 biologic-naive patients initiating biologics. After matching, patient characteristics were similar between cohorts. Twelve-month treatment persistence was similar for biologic-naive patients initiating apremilast vs biologics (32.1% vs 33.2%; p?=?0.7079). While persistent on therapy up to 12?months, per-patient per-month (PPPM) total healthcare costs were significantly lower among biologic-naive cohorts initiating apremilast vs biologics ($2,214 vs $5,184; p?p?p?p?Limitations: Data were limited to individuals with United Healthcare commercial and Medicare Advantage insurance plans, and may not be generalizable to psoriasis patients with other insurance or without health insurance coverage.

Conclusion: Biologic-naive patients with similar patient characteristics receiving apremilast vs biologics had significantly lower PPPM costs, even when they switched to biologics during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize psoriasis care while reducing healthcare costs.     

Inflammatory bowel disease: healthcare costs for patients who are adherent or non-adherent with infliximab therapy

Objective:

Healthcare costs of inflammatory bowel disease are substantial. This study examined the effect of adherence versus non-adherence on healthcare costs in patients with inflammatory bowel disease.

Methods:

Adults who started infliximab treatment between 2006 and 2009 and had a diagnosis of inflammatory bowel disease were identified from MarketScan Databases. Medication adherence was defined as an infliximab medication possession ratio of 80% or greater in the first year. Mean treatment effects (adherence versus non-adherence) on costs in adherent patients were estimated with propensity-weighted generalized linear models.

Results:

A total of 1646 patients were identified. Significant variables in the model used to develop propensity weights were age, year of infliximab initiation, having Medicare coverage, presence of supplementary diagnoses, office as the place of service for infliximab initiation, prior aminosalicylate use, prior outpatient costs, number of prior outpatient visits, and number of prior colonoscopies. Mean total costs in adherent (n?=?674) and propensity-weighted non-adherent (n?=?972) patients were $41,713 versus $47,411 overall (p?p?p?p?p?p?=?0.460).

Limitations:

Costs associated with infliximab administration (infusions, adverse events) were captured in healthcare costs (inpatient, outpatient, and emergency room), not in infliximab costs. The influence of adherence on indirect costs (e.g., time lost from work) could not be determined. Reasons for non-adherence were not available in the database.

Conclusions:

In patients who were adherent to infliximab treatment (a medication possession ratio of 80% or greater in the first year), adherence versus non-adherence was associated with lower total healthcare costs, supporting the overall value of infliximab adherence in patients with inflammatory bowel disease.     

One-year follow-up healthcare costs of patients hospitalized for transient ischemic attack or ischemic stroke and discharged with aspirin plus extended-release dipyridamole or clopidogrel

Abstract

Objective:

To examine healthcare costs among patients hospitalized for transient ischemic attack or ischemic stroke (TIA/stroke) and prescribed aspirin plus extended-release dipyridamole (ASA-ERDP) or clopidogrel (CLOPID) within 30 days post-discharge using a retrospective claims database from a large US managed care organization.

Methods:

Adult patients with ≥1 hospitalizations for TIA/stroke between January 2007–July 2009 and ≥1 claims for an oral anti-platelet (OAP) were observed for 1 year before and after the first TIA/stroke hospitalization or until death, whichever came first. Cohorts were defined by the first claim for ASA-ERDP or CLOPID within 30 days post-discharge. A generalized linear model, adjusting for demographics, baseline comorbidities and costs, compared total follow-up costs (medical?+?pharmacy) between ASA-ERDP and CLOPID patients.

Results:

Of 6377 patients (2085 ASA-ERDP; 4292 CLOPID) who met the selection criteria, mean (SD) age was 69 (13) years and 50% were male. Unadjusted mean total follow-up costs were lower for ASA-ERDP than CLOPID ($26,201 vs $30,349; p?=?0.002), of which average unadjusted medical and pharmacy costs were $22,094 vs $26,062 (p?=?0.003) and $4107 vs $4288 (p?=?0.119), respectively. Multivariate modeling indicated that the following were associated with higher total costs (all p?<?0.05): higher baseline Quan-Charlson comorbidity score, history of atrial fibrillation and myocardial infarction, index stroke hospitalization, death post-discharge, and index CLOPID use. Adjusted mean total follow-up costs for CLOPID were 9% higher than ASA-ERDP (cost ratio: 1.09; p?=?0.038).

Conclusion:

In this study, compared to CLOPID patients, ASA-ERDP patients were observed to have lower total costs 1 year post-discharge TIA/stroke hospitalization, driven primarily by lower medical costs. Further research into the real-world impact of OAP therapies on clinical and economic outcomes of patients with stroke/TIA is warranted. The findings of this study should be considered within the limitations of an administrative claims analysis, as claims data are collected for the purpose of payment.     

Healthcare costs for Crohn’s disease patients treated with infliximab: a propensity weighted comparison of the effects of treatment adherence

Objective:

The objective for the research was to evaluate the direct healthcare costs for Crohn’s disease (CD) patients categorized by adherence status.

Methods:

Adult patients with ≥1 claim for infliximab and ≥2 claims for CD who were continuously insured for 12 months before and after their first infliximab infusion (index date) were identified in a 2006–2009 US managed care database. Patients were excluded if they had rheumatoid arthritis claims, received infliximab billed as a pharmacy benefit, or received another biologic drug. Patients were categorized as being either adherent or intermittently adherent to infliximab using a pre-defined algorithm. Total and component direct costs, CD-related costs, rates of surgery, and days of hospitalization were estimated for the 360-day post-index period. Propensity weighted generalized linear models were used to adjust the cost estimates for potential confounding variables.

Results:

The total propensity weighted cost for infliximab adherent patients was $40,425 (95% CI?=?[$38,686, $42,242]), compared to $41,082 (95% CI?=?[$38,163, $44,223]) for the intermittently adherent (p?=?0.71). However, adherent patients had lower total direct medical costs, exclusive of infliximab, that were $13,097 (95% CI?=?[$12,141, $14,127]) compared with $20,068 (95% CI?=?[$17,676, $22,784]) for intermittently adherent patients as a result of substantially lower hospital and outpatient costs (p?Conclusions:

Greater drug-related costs for infliximab adherent patients were offset by lower costs from hospitalization and outpatient visits. These findings indicate that adherent patients have improved clinical outcomes, at a similar aggregate cost, than patients who are only intermittently adherent to therapy.     

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

Abstract

Objective:

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).

Methods:

Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.

Results:

Of 52,274 patients, 53% (n?=?27,457) were male, 71% (n?=?37,271) were ≥65?years, and three LABD cohorts accounted for over 90% of the sample [53% (n?=?27,654) salmeterol/fluticasone propionate, 23% (n?=?11,762) tiotropium, and 15% (n?=?7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p?<?0.001), formoterol fumarate (p?=?0.032), salmeterol (p?=?0.004), or with combination therapy (p?<?0.001) had higher COPD-related costs and a greater risk of inpatient admission (p?<?0.01 for all) versus tiotropium.

Limitations:

These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.

Conclusions:

Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs     

Comparing treatment adherence of lisdexamfetamine and other medications for the treatment of attention deficit/hyperactivity disorder: a retrospective analysis

Abstract

Objective:

To assess treatment adherence in attention deficit/hyperactivity disorder (ADHD) patients initiated on Lisdexamfetamine (LDX) vs other FDA-approved stimulants and non-stimulant medications.

Methods:

ADHD patients initiated on an ADHD medication (index medication) were selected from a large US administrative claims database. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6–17 years old), previously treated children and adolescents, treatment-naïve adults (over 18 years old), and previously treated adults. Furthermore, based on their index medication, patients were classified into seven mutually exclusive treatment groups: LDX, atomoxetine (ATX), osmotic release methylphenidate hydrochloride long acting (OROS MPH), other methylphenidate/dexmethylphenidate long acting (MPH LA) and short acting (MPH SA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long acting (AMPH LA). Treatment adherence (proportion of days covered by the index medication ≥0.8) over a 12-month period was compared across treatment groups using multivariate logistic regression models.

Results:

In children and adolescents, LDX patients were more likely to be adherent compared to patients in each of the other treatment groups, except in treatment-naïve patients where LDX patients had a similar likelihood (p?=?0.6925) and were less likely (p?=?0.0004) to be adherent compared to ATX and OROS MPH patients, respectively. In adults, the LDX treatment group was also more likely to be adherent compared to each of the other treatment groups, except compared to AMPH LA, where statistically insignificant differences were observed (previously treated: p?=?0.6471, treatment-naïve: p?=?0.0733).

Limitations:

ADHD severity information was not available in the database. Accordingly, this study did not control for ADHD severity.

Conclusion:

Overall, LDX-treated patients demonstrated a better treatment adherence compared to patients initiated on other ADHD medications, except for AMPH LA in adult and OROS MPH and ATX in treatment-naïve children and adolescents.     

Healthcare costs associated with nephrology care in pre-dialysis chronic kidney disease patients

Abstract

Objective:

To compare the healthcare costs of pre-dialysis chronic kidney disease (CKD) patients cared for in a nephrology clinic setting versus other care settings.

Methods:

An analysis of health claims between 01/2002 and 09/2007 from the Ingenix Impact Database was conducted. Inclusion criteria were ≥18 years of age, ≥1 ICD-9 claim for CKD, and ≥1 estimated glomerular filtration rate (eGFR) value of <60?mL/min/1.73?m². Patients were classified in the nephrology care cohort if they were treated in a nephrology clinic setting at least once during the study period. Univariate and multivariate analyses were conducted to compare average annualized healthcare costs of patients in nephrology care versus other care settings.

Results:

Among the 20,135 patients identified for analysis, 1,547 patients were cared for in a nephrology clinic setting. Nephrology care was associated with lower healthcare costs with an unadjusted cost savings of $3,049 ($11,303 vs. $14,352, p?=?0.0014) and a cost ratio of 0.8:1 relative to other care settings. After adjusting for covariates, nephrology care remained associated with lower costs (adjusted cost savings: $2,742, p?=?0.006).

Limitations:

Key limitations included potential inaccuracies of claims data, the lack of control for patients’ ethnicity in the calculation of eGFR values, and the presence of potential biases due to the observational design of the study.

Conclusions:

The current study demonstrated that pre-dialysis CKD patients treated in nephrology clinics were associated with significantly lower healthcare costs compared with patients treated in other healthcare settings.     

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

Abstract

Objective:

To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.

Methods:

Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.

Results:

The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p?=?0.26 vs etanercept; p?=?0.86 vs adalimumab), adalimumab (p?=?0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p?<?0.001 vs etanercept; p?=?0.18 vs adalimumab), 0.63 for adalimumab (p?=?0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).

Conclusions:

Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.