Switching of biologic disease modifying anti-rheumatic drugs in patients with rheumatoid arthritis in a real world setting

Objectives:

This study examined total healthcare costs and rates of patients with rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic drug (bDMARD) therapy in a real world setting.

Methods:

A retrospective longitudinal analysis was conducted in patients with RA using IMS PharMetrics Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow-up. The second-line cohort included patients initiating a bDMARD with evidence of a different bDMARD within the previous 2 years and with 12 months of continuous follow-up. Switching was defined as a different bDMARD claim within a 200% gap in days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD in the follow-up period. Monthly total healthcare costs for switchers and non-switchers and rates of bDMARD switching were examined. Switch rates for each bDMARD were also compared.

Results:

First-line switchers had significantly higher monthly total healthcare costs after the switch than non-switchers ($3759 vs $2343; p?p?Limitations:

There are no clinical data available in this database and, therefore, this study did not examine the clinical drivers of healthcare costs and switch rates.

Conclusions:

Monthly total healthcare costs were higher for bDMARD switchers following the switch compared to non-switchers. Patients on abatacept switched less frequently than patients on anti-TNFs. This study highlights the need to identify patients who are likely to switch in order to ensure they receive the appropriate therapy which may improve outcomes and decrease healthcare costs.     

The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rheumatoid arthritis patients

Aims: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically.

Materials and methods: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010–2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept.

Results: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p?p?p?p?=?.021), and numerically lower all-cause costs ($4,444 vs $4,741, p?=?0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p?=?.031), and numerically higher ED visits (IRR = 1.32, p?=?.093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p?Limitations and conclusions: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.     

Comparison of second-generation antipsychotic treatment on psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder

Abstract

Objective:

To compare second-generation antipsychotics on time to and cost of psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder.

Methods:

Retrospective study using healthcare claims from 10 US state Medicaid programs. Included beneficiaries were aged 18–64, initiated a single second-generation antipsychotic (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) between 1/1/2003–6/30/2008 (initiation date?=?index), and had a medical claim with an ICD-9-CM diagnosis code for bipolar disorder. A 360-day post-index period was used to measure time to and costs of psychiatric hospitalization (inpatient claims with a diagnosis code for a mental disorder [ICD-9-CM 290.xx–319.xx] in any position). Cox proportional hazards models and Generalized Linear Models compared time to and costs of psychiatric hospitalization, respectively, in beneficiaries initiating aripiprazole vs each other second-generation antipsychotic, adjusting for beneficiaries’ baseline characteristics.

Results:

Included beneficiary characteristics: mean age 36 years, 77% female, 80% Caucasian, aripiprazole (n?=?2553), mean time to psychiatric hospitalization or censoring?=?85 days; olanzapine (n?=?4702), 81 days; quetiapine (n?=?9327), 97 days; risperidone (n?=?4377), 85 days; ziprasidone (n?=?1520), 82 days. After adjusting for baseline characteristics, time to psychiatric hospitalization in beneficiaries initiating aripiprazole was longer compared to olanzapine (hazard ratio [HR]?=?1.52, p?<?0.001), quetiapine (HR?=?1.40, p?<?0.001), ziprasidone (HR?=?1.33, p?=?0.032), and risperidone, although the latter difference did not reach significance (HR?=?1.18, p?=?0.13). The adjusted costs of psychiatric hospitalization in beneficiaries initiating aripiprazole were significantly lower compared to those initiating quetiapine (incremental per-patient per-month difference?=?$42, 95% CI?=?$16–66, p?<?0.05), but not significantly lower for the other comparisons.

Limitations:

This study was based on a non-probability convenience sample of the Medicaid population. Analyses of administrative claims data are subject to coding and classification error.

Conclusions:

Medicaid beneficiaries with bipolar disorder initiating aripiprazole had significantly longer time to psychiatric hospitalization than those initiating olanzapine, quetiapine, or ziprasidone, and significantly lower adjusted costs for psychiatric hospitalization than those initiating quetiapine.     

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.     

Outcomes of tumor necrosis factor inhibitor cycling versus switching to a disease-modifying anti-rheumatic drug with a new mechanism of action among patients with rheumatoid arthritis

Objectives: To examine treatment patterns, treatment effectiveness, and treatment costs for 1 year after patients with rheumatoid arthritis switched from a tumor necrosis factor inhibitor (TNFi) (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab), either cycling to another TNFi (“TNFi cyclers”) or switching to a new mechanism of action (abatacept, tocilizumab, or tofacitinib) (“new MOA switchers”).

Methods: This retrospective cohort study used administrative claims data for a national insurer. Treatment persistence (without switching again, restarting, or discontinuing), treatment effectiveness (defined below), and costs were assessed for the 12-month post-switch period. Patients were “effectively treated” if they satisfied all six criteria for a treatment effectiveness algorithm (high adherence, no dose increase, no new conventional synthetic disease-modifying anti-rheumatic drug, no subsequent switch in therapy, no new/increased oral glucocorticoids, and <2 glucocorticoid injections). Multivariable logistic models were used to adjust for baseline factors.

Results: The database included 581 new MOA switchers and 935 TNFi cyclers. New MOA switchers were 39% more likely than TNFi cyclers to persist after the switch (odds ratio [OR]?=?1.39; 95% confidence interval [CI]?=?1.12–1.74; p?=?.003) and 36% less likely to switch therapy again (OR?=?0.64; 95% CI?=?0.51–0.81; p?p?=?.006). New MOA switchers had 16% lower drug costs than TNFi cyclers (cost ratio?=?0.84; 95% CI?=?0.79–0.88; p?p?Limitations: Claims payments may not reflect rebates or other cost offsets. Medical and pharmacy claims do not include clinical end-points or reasons that lead to new MOA switching vs TNFi cycling.

Conclusions: These results support switching to a new MOA after a patient fails treatment with a TNFi, which is consistent with recent guidelines for the pharmacologic management of established rheumatoid arthritis.     

Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population

Abstract

Objective:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys (lupus nephritis) and the central nervous system (neuropsychiatric lupus, or NPSLE). The healthcare costs and resource utilization associated with treating lupus nephritis and NPSLE in a large US managed care plan were studied.

Methods:

SLE subjects ≥18 years of age and with claims-based evidence of nephritis or neuropsychiatric conditions were identified from a health plan database. An index date was set as a randomly drawn date from all qualifying claims during 2003–2008 for study subjects. Subjects were matched on the basis of demographic and clinical characteristics to unaffected controls. Costs and resource use were determined during a fixed 12-month post-index period.

Results:

Nine hundred and seven lupus nephritis subjects were matched to controls, and 1062 subjects with NPSLE were matched to controls. Mean overall post-index healthcare costs were significantly higher among subjects with lupus nephritis in comparison to matched controls ($33,472 vs $5347, p?<?0.001). Similarly, mean overall post-index healthcare costs were significantly higher among subjects with NPSLE compared to controls ($30,341 vs $4646, p?<?0.001). Subjects with lupus nephritis or NPSLE had higher mean post-index numbers of ambulatory visits, specialist visits, emergency department visits and inpatient hospital stays, compared to controls (all p?<?0.001).

Limitations:

Additional research, such as medical chart review, could provide validation for the claims-based identification of lupus nephritis and NPSLE subjects. Also, indirect costs were not evaluated in this study.

Conclusion:

Subjects with lupus nephritis or NPSLE have high costs and resource use, compared to unaffected controls.     

The real-world economic impact of home-based video electroencephalography: the payer perspective

Abstract

Aims: Electroencephalography (EEG) is an established method to evaluate and manage epilepsy; video EEG (VEEG) has significantly improved its diagnostic value. This study compared healthcare costs and diagnostic-related outcomes associated with outpatient vs inpatient VEEG among patients with epilepsy in the US.

Materials and methods: This study used Truven MarketScan Commercial and Medicare Supplemental claims databases. Patients with a VEEG between July 1, 2013 and December 31, 2016 were identified. Index event was the first VEEG claim, which was used to determine inpatient and outpatient cohorts. Continuous health plan enrollment 6?months pre- and 12?months post-index VEEG was required. Primary outcomes were costs during the index event and 12?months post index. A generalized linear model with gamma distribution and a log link was used to estimate adjusted index and post-index costs.

Results: Controlling for baseline differences, epilepsy-related cost of index VEEG was significantly lower for the outpatient ($4,098) vs the inpatient cohort ($13,821; p?<?0.0001). The cost differences observed at index were maintained in the post-index period. The 12-month post-index epilepsy-related costs were lower in the outpatient cohort ($6,114 vs $12,733, p?<?0.0001). Time from physician referral to index VEEG was significantly shorter in the outpatient cohort (30.6 vs 42.5?days). Patients in the inpatient cohort were also more likely to undergo an additional subsequent follow-up inpatient VEEG (p?<?0.0001).

Limitations: Administrative claims data have limitations, including lack of data on clinical presentation, disease severity, and comprehensive health plan information. Generalizability may be limited to a US insured population of patients who met study criteria.

Conclusions: Index VEEG was less costly in an outpatient vs inpatient cohort, and costs were lower during the follow-up period of 12?months, suggesting that outpatient VEEG can be provided to appropriate patients as a less costly option. There were fewer follow-up tests in the outpatient cohort with similar pre- and post-index diagnoses.     

Healthcare resource use and costs of privately insured patients who switch,discontinue, or persist on anti-muscarinic therapy for overactive bladder

Objectives:

To compare the healthcare costs of patients with overactive bladder (OAB) who switch vs persist on anti-muscarinic agents (AMs), describe resource use and costs among OAB patients who discontinue AMs, and assess factors associated with persisting vs switching or discontinuing.

Methods:

OAB patients initiating an AM between January 1, 2007 and March 31, 2012 were identified from a claims database of US privately insured beneficiaries (n?≈?16 million) and required to have no AM claims in the 12 months before AM initiation (baseline period). Patients were classified as persisters, switchers, or discontinuers, and assigned a study index date based on their AM use in the 6 months following initiation. Baseline characteristics, resource use, and costs were compared between persisters and the other groups. Resource use and costs in the 1 month before and 6 months after the study index date (for switchers, the date of index AM switching; for persisters, a randomly assigned date to reflect the distribution of the time from AM initiation to switching among switchers) were also compared between persisters and switchers in unadjusted and adjusted analyses. Factors associated with persisting vs switching or discontinuing were assessed.

Results:

After controlling for baseline characteristics and costs, persisters vs switchers had significantly lower all-cause and OAB-related costs in both the month before (all-cause $1222 vs $1759, OAB-related $142 vs $170) and 6 months after the study index date (all-cause $7017 vs $8806, OAB-related $642 vs $797). Factors associated with switching or discontinuing vs persisting included index AM, younger age, and history of UTI.

Conclusion:

A large proportion of OAB patients discontinue or switch AMs shortly after initiation, and switching is associated with higher costs.     

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.     

The economic burden of psoriasis with high comorbidity among privately insured patients in the United States

Objective: To evaluate the impact of comorbidities on healthcare resource use (HRU), and direct and indirect work-loss-related costs in psoriasis patients.

Methods: Adults with psoriasis (≥2 diagnoses, the first designated as the index date) and non-psoriasis controls (no psoriasis diagnoses, randomly generated index date) were identified in a US healthcare claims database of privately-insured patients (data between January 2010 and March 2017 were used). Psoriasis patients were stratified based on the number of psoriasis-related comorbidities (0, 1–2, or ≥3) developed during the 12?months post-index. All outcomes were evaluated during the follow-up period, spanning the index date until the end of continuous health plan eligibility or data cut-off. HRU and costs per-patient-per-year (PPPY) were compared in psoriasis and non-psoriasis patients with ≥12?months of follow-up.

Results: A total of 9,078 psoriasis (mean age?=?44?years, 51% female) and 48,704 non-psoriasis (mean age?=?41?years, 50% female) patients were selected. During the 12?months post-index, among psoriasis vs non-psoriasis patients, 71.0% vs 83.0% developed no psoriasis-related comorbidities, 26.3% vs 16.0% developed 1–2, and 2.6% vs 1.0% developed ≥3 psoriasis-related comorbidities. Compared to non-psoriasis patients, psoriasis patients had more HRU including outpatient visits (incidence rate ratios [IRRs]?=?1.52, 2.03, and 2.66 for 0, 1–2, and ≥3 comorbidities, respectively [all p?p?p?p?Conclusions: HRU and cost burden of psoriasis are substantial, and increase with the development of psoriasis-related comorbidities.     

Treatment patterns and healthcare system burden of managed care patients with suspected pulmonary arterial hypertension in the United States

Abstract

Objectives:

To describe treatment patterns and healthcare burden among individuals with suspected pulmonary arterial hypertension (PAH), as identified through a practice guideline-based healthcare claims algorithm.

Methods:

Adults with evidence of PAH from 1 January 2004 (commercial and Medicaid) or 1 July 2006 (Medicare Advantage) through 30 June 2008 were identified. Given the lack of an ICD-9 code for PAH, an algorithm was developed requiring: (1) ≥1 claim for PAH medication (index date); (2) ≥1 claim with a pulmonary hypertension diagnosis code in the 6-month pre-index period (baseline) or within 90 days post-index; (3) a right heart catheterization or pulmonary hypertension-related inpatient stay during baseline or within 90 days post-index; and (4) continuous health plan enrollment for 6 months pre-index and ≥6 months post-index. Patients with PAH-specific medications during baseline were excluded. Treatment patterns, healthcare utilization, and costs were assessed during the period ending with the earlier of health plan disenrollment or 31 December 2008.

Results:

Among the 521 included patients, 69% were female. Most patients (94%) initiated treatment with monotherapy (most commonly sildenafil or bosentan), and 12.7% of all patients augmented their therapy by the end of the observation period. The medication possession ratio was 0.96 each for ambrisentan (SD?=?0.04), bosentan (SD?=?0.04), and sildenafil (SD?=?0.05). Overall, 72.6% of patients discontinued therapy with a mean of 149 (SD?=?170) days until discontinuation. A mean (SD) of 2.14 (1.82) all-cause office and 1.64 (1.98) outpatient visits occurred per patient per month. Mean PAH-related healthcare costs were $6617 per patient per month, comprising 71% of all-cause costs. The guideline-based algorithm may not have perfectly captured patients with PAH.

Conclusions:

Patients with suspected PAH were likely to initiate treatment with oral monotherapy, had high compliance rates, and received close ambulatory follow-up. PAH-related costs constituted the majority of all-cause healthcare costs.     

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting

Aims: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013–September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up.

Results: During the follow-up, risks for all-cause (hazard ratio [HR]?=?1.44, 95% confidence interval [CI]?=?1.2–1.7) and MB-related (HR?=?1.57, 95% CI?=?1.0–2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p?=?.002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p?=?.096). Risk for all-cause hospitalization (HR?=?1.98, 95% CI?=?1.6–2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR?=?2.22, 95% CI?=?1.9–2.5) and MB-related (HR?=?2.05, 95% CI?=?1.4–3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p?=?.025) and MB-related medical costs ($96 vs $212 PPPM, p?=?.026) were significantly lower for patients treated with apixaban vs warfarin.

Limitations: This retrospective database analysis does not establish causation.

Conclusions: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.