Karthik Ramakrishnan

Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers.

Abstract Objective: To compare persistence and adherence among patients with chronic obstructive pulmonary disease (COPD) treated with either multiple- or single- long-acting maintenance inhalers. Methods: Patients with ≥2 COPD medical claims and ≥2 prescriptions for a long-acting inhaler within 1 year were classified as single- or multiple-inhaler users based on their treatment regimen (MarketScan database; 2004–2008) and matched on demographics and statistically significant baseline characteristics. Persistence, analyzed via time to treatment discontinuation, and treatment adherence, measured by proportion of days covered (PDC), were compared between the two groups over a 12-month period. Sensitivity analyses were conducted in patients with poorly and well-controlled disease. Results: A total of 23,494 patients were grouped into 11,747 matched pairs. After adjusting for confounding factors, multiple-inhaler users had a significantly higher discontinuation rate [Hazard ratio = 1.40, p < 0.0001] compared with single-inhaler users. Multiple-inhaler users were less likely to be adherent than single-inhaler users with an average PDC of 0.51 (SD = 0.272) vs. 0.55 (SD = 0.279), respectively (p < 0.0001). These results were consistent for the poorly- and well-controlled disease groups. Conclusions: Multiple long-acting inhaler users demonstrated lower treatment persistence and adherence rates than single long-acting inhaler users. Limitations of the study are related to the retrospective, observational design and use of claims data.

Clinical and economic outcomes of multiple versus single long-acting inhalers in COPD.

OBJECTIVE To compare healthcare resource utilization and healthcare costs between COPD patients who used multiple long-acting inhalers versus those who used a single long-acting inhaler. METHODS COPD patients meeting study inclusion criteria were identified in the Market Scan database (2004-2008) and were classified as being a multiple- or single-inhaler user. 11,747 multiple- and single-inhaler users were matched on baseline characteristics to balance disease severity. Patients were followed for 12 months. Incremental differences between the two groups were estimated for: number of exacerbations; time to first exacerbation; all-cause and COPD-related inpatient admissions, inpatient days, emergency room visits, urgent care visits, outpatient visits, and other medical services visits; all-cause and COPD-related healthcare costs. Multivariate regression analyses were also used to control for a number of potentially confounding factors. RESULTS After controlling for a number of potentially confounding factors, multiple-inhaler users experienced significantly more exacerbations (0.52; p < .0001) and had a higher risk of exacerbation (HR = 1.40; p < .0001) than single-inhaler users. Multiple-inhaler users also incurred significantly more inpatient admissions (IRR = 1.15; p < .0001), inpatient days (IRR = 1.20; p < .0001), urgent care visits (IRR = 1.10; p = 0.0026), outpatient visits (IRR = 1.06; p < .0001), and other medical services visits (IRR = 1.12; p = <.001) than single-inhaler users, resulting in significantly higher all-cause health care costs (

Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: Comparison of adverse event–free response days in the CHAMPION trial

3,319; p < .0001). Results of COPD-related resource use and costs were comparable. CONCLUSIONS After controlling for a number of potentially confounding factors, multiple-inhaler users had more exacerbations, a higher risk of exacerbation, and higher healthcare resource utilization and costs compared to single-inhaler users.

Economic Impact of Therapeutic Substitution of a Brand Selective Serotonin Reuptake Inhibitor with an Alternative Generic Selective Serotonin Reuptake Inhibitor in Patients with Major Depressive Disorder

BACKGROUND The Comparative Study of Humira versus Methotrexate (MTX) versus Placebo in Psoriasis Patients (CHAMPION) demonstrated superior efficacy of biologic over conventional systemic immunosuppressant therapy in psoriasis. OBJECTIVE We sought to compare the risk-benefit profile of adalimumab (ADA), MTX, and placebo using data from CHAMPION. METHODS Patients randomized to ADA (n = 107), MTX (n = 110), or placebo (n = 53) were followed up for 16 weeks. Response (≥75% improvement in Psoriasis Area and Severity Index), days free of adverse events (AEs), moderate to severe AEs, infection-related AEs, and study drug-related AEs were analyzed. RESULTS ADA treatment was associated with substantially more days (SD) of AE-free response compared with MTX or placebo treatment, respectively: 36.9 (31.1) versus 8.3 (15.9) or 6.7 (18.1) days of response free of any AEs, 43.8 (31.9) versus 11.1 (19.9) or 7.9 (19.9) days of response free of moderate to severe AEs, 48.5 (29.2) versus 12.4 (21.7) or 9.2 (21.8) days of response free of infection-related AEs, and 44.6 (31.4) versus 11.8 (21.1) or 10.0 (24.0) days free of study drug-related AEs (all P < .0001 for ADA vs MTX or placebo). LIMITATIONS This clinical trial-based analysis may not have captured the full spectrum of AEs in the actual clinical setting. The short (16-week) duration of the trial limited the ability to capture some important but uncommon AEs associated with long-term ADA or MTX use. CONCLUSION With 4 times as many AE-free response days, ADA demonstrated a superior benefit-risk profile.

Persistence with nebivolol in the treatment of hypertension: a retrospective claims analysis.

Background To reduce pharmacy costs, managed care organizations encourage therapeutic substitution from brand to a generic product. However, little is known about whether these cost-containment strategies can also potentially lower total expenditures for payers in treatment of major depressive disorder (MDD). Objective: To compare economic outcomes of patients with MDD who were switched from a brand selective serotonin reuptake inhibitor (SSRI) to an alternative generic SSRI for nonmedical reasons versus patients who continued on the brand SSRI. Methods: Adult MDD patients in the Ingenix Impact Database (2003–2007) were considered “switchers” if they received treatment with a brand SSRI and were later switched to an alternative generic SSRI for nonmedical reasons. Patients who remained on the brand SSRI (nonswitchers) were matched 1:1 with switchers. All-cause, mental health-related, and MDD-related rates of hospitalizations/emergency department (ED) visits and costs over 6 months were compared both descriptively and by using adjusted regression models. A subgroup analysis on patients who were switched from escitalopram (Lexapro) to an alternative generic SSRI was also performed. Results: The study included 4449 matched pairs. Compared with nonswitchers, switchers had higher risk of all-cause, mental health–related, and MDD-related use of hospitalizations/ED visits (OR 1.15, 1.34, and 1.54, respectively; all p < 0.01) and higher risk-adjusted mental health–related and MDD-related medical costs (

Effects of Adalimumab versus Placebo on Risk of Symptom Worsening in Psoriasis and Subsequent Impacts on Health-Related Quality-of-Life

219 and

Remission of major depressive disorder without adverse events: a comparison of escitalopram versus serotonin norepinephrine reuptake inhibitors.

222, respectively; both p < 0.05). Subgroup analysis on escitalopram showed similar results; switchers experienced higher risk of any-cause, mental health–related, and MDD-related use of hospitalizations/ED visits (OR 1.21, 1.41, and 1.53, respectively; all p<0.01) and higher risk-adjusted MDD-related medical costs (

Cardiovascular and economic outcomes after initiation of atorvastatin versus simvastatin in an employed population stratified by cardiovascular risk.

151; p<0.05). Conclusions: Compared with patients who continued on their patented SSRIs, patients who switched to a generic SSRI incurred more resource use of hospitalizations/ED visits and higher MDD-related health-care costs. The effects of therapeutic substitution should be carefully examined, because use of generic alternatives may not be a cost-saving strategy when total health-care costs are considered.

PMH38 THE ECONOMIC IMPACT OF GENERIC SWITCHING FOR PATIENTS WITH MAJOR DESPRESSIVE DISORDER (MDD) TREATED WITH ESCITALOPRAM OR A PATENTED SSRI

Abstract Objective: Examine drug persistence by evaluating the hazard of discontinuation and of switching to different antihypertensive drugs in patients initiating treatment with a recently approved β-blocker, nebivolol, versus other β-blockers. Methods: This retrospective analysis included all patients diagnosed with hypertension in the MarketScan Database (January 2007 – December 2008) with at least two medical claims and no prior β-blocker prescriptions within 6 months of the initial prescription date. Multivariate Cox proportional hazard models (adjusted for baseline differences in demographics, previous use of other antihypertensive medications, initial doses and supply of medication, and number of distinct prescriptions at baseline) were used to assess the hazard of discontinuation, defined as the first prescription gap of ≥30 days, and to assess the hazard of switching to another antihypertensive drug, defined as a prescription fill for another antihypertensive drug within 15 days before and 30 days after discontinuation of the initial β-blocker. Results: Of the 173,200 patients included in the study population, the adjusted hazard of discontinuation for nebivolol-initiated patients was 8–20% lower than that of patients who initiated treatment with atenolol (hazard ratio [HR] 0.82, p < 0.001), metoprolol (HR 0.91, p < 0.001), carvedilol (HR 0.92, p < 0.001), or other β-blockers (HR 0.80, p < 0.001). The adjusted hazard of nebivolol-treated patients switching to a different antihypertensive medication was 12–22% lower than that of the other four β-blocker cohorts (atenolol: HR 0.80, p < 0.001; metoprolol: HR 0.86, p < 0.001; carvedilol: HR 0.88, p < 0.001; other β-blockers: HR 0.78, p < 0.001). Sensitivity analyses defined discontinuation as prescription gaps of ≥45 days and ≥60 days and showed a lower hazard of discontinuation among patients initiating nebivolol than among patients initiating all other drug cohorts (p < 0.001). Limitations: Comparisons of non-randomized treatment groups may be confounded by unobserved differences in patients’ baseline characteristics. Conclusions: Initiation with nebivolol was associated with greater persistence than initiation with atenolol, carvedilol, metoprolol, or other β-blockers.

PGI15 The Economic Burden of Unmet Treatment Needs in Medicaid Patients with Chronic Constipation

AbstractBackground: Rates and impacts of worsening symptoms in patients with psoriasis have not been well characterized. Objectives: To assess the risk of clinically relevant worsening of psoriasis symptoms in patients treated with adalimumab versus placebo and to determine the health-related quality-of-life (HRQOL) impacts of such worsening. Methods: The cumulative incidence of worsening was compared for adalimumab (40 mg every other week following an 80 mg induction dose) versus placebo using data from two phase III randomized, placebo-controlled trials (CHAMPION and REVEAL). Clinically relevant worsening of psoriasis was defined as a follow-up visit with a ≥25% increase in the Psoriasis Area and Severity Index (PASI) from baseline or a ≥5-unit increase in the Dermatology Life Quality Index from baseline during the initial 16-week double-blind treatment periods. Patients with versus without worsening were compared in terms of pain, work productivity and activity impairment (WPAI) and the mental and physical component summary (MCS and PCS) scores of the Short-Form 36 Health Survey. A subgroup analysis was performed for patients with PASI 10-20 at baseline. Results: The 17-week risk of clinically relevant worsening was 37.0% (95% CI 26.1, 46.3) for placebo (n = 445) and 4.2% (95% CI 2.0, 6.3) for adalimumabtreated patients (n = 914) [p< 0.0001]. Patients with versus without worsening experienced substantially increased pain, increased WPAI and greater impairment in MCS and PCS. Results were similar for patients with PASI 10–20 at baseline. Limitations: The short study duration may not reflect long-term outcomes. Conclusion: Clinically relevant worsening of psoriasis symptoms was associated with substantial worsening of HRQOL. Adalimumab treatment was associated with a substantially reduced risk of clinically relevant worsening.