OBJECTIVE: This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.
METHODS: This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005-2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose > recommended label dose, (2) average ending dispensed dose > maintenance dose, and (3) average dose after maintenance dose > maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.
RESULTS: Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional dose escalation rates and magnitudes of escalation were directionally consistent with national rates. Etanercept had the lowest cost per treated RA patient ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030).
LIMITATIONS: Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ∼50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.
CONCLUSIONS: In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.
OBJECTIVE: To describe dosing patterns of etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA) patients in US managed care.
METHODS: This retrospective analysis included adult (18-64 years) RA patients in the HealthCore Integrated Research Database with ≥ 1 claim for etanercept, adalimumab, or infliximab between 7/1/2007 and 1/31/2010. Patients had 6 months pre-index and 12 months post-index claim eligibility. Patients without any TNF blocker claim during the pre-index period were considered new patients and patients with a TNF blocker claim during the pre-index period were considered continuing patients. Persistence, discontinuation, switch, and dose escalation patterns were evaluated. Patients with 1-year persistence were evaluated for dose escalation using two methods: (1) average weekly dose and (2) increase from 50 mg to 75 mg or 100 mg weekly of etanercept or from 40 mg every other week to 40 mg weekly of adalimumab or increase in vial or decreased infusion interval for infliximab.
RESULTS: Data from 2426 patients were analyzed (1595 etanercept; 417 adalimumab; 414 infliximab). Persistence ≥ 1 year on index medication was reported in 62.2% and 89.2% of new and continuing patients on etanercept, respectively, 66.0% and 94.0% on adalimumab, and 68.9% and 96.4% on infliximab. Discontinuation occurred in 19.7% and 7.9% of new and continuing patients on etanercept, respectively, 20.6% and 4.5% on adalimumab, and 18.8% and 2.1% on infliximab. Switching occurred in 12.2% and 4.3% of new and continuing patients on etanercept, respectively, 9.1% and 1.8% on adalimumab, and 10.4% and 2.1% on infliximab. Dose escalation was lower with etanercept (0.4-2.6%) than adalimumab (12.6-24.3%) or infliximab (40.0-79.5%) (P < 0.0001).
CONCLUSIONS: Discontinuation and switching were common within 1 year of initiating etanercept, adalimumab, and infliximab in patients with RA in this analysis. Study limitations included the restricted patient age range; analysis of three TNF blockers; study period (prior to approval of additional agents); and missing reasons for treatment changes.
OBJECTIVES: This retrospective, multicentre, observational study aimed to assess the mean annual doses and associated costs of three anti-tumour necrosis factor agents in daily clinical practice in rheumatoid arthritis patients, correlating these costs with disease activity.
METHODS: Adult rheumatoid arthritis patients were treated and followed at the Rheumatology departments of two Spanish hospitals for at least 6 months, with adalimumab, etanercept or infliximab over a 4-year period. ANOVA and multivariate statistical analyses of dosing patterns, disease activity and annualised costs were carried out.
RESULTS: A total of 198 patients, comprising 215 cases, met the inclusion criteria (73 on adalimumab, 81 etanercept and 61 infliximab). Compared to recommended doses, mean doses of adalimumab and etanercept decreased by 7% and 19%, respectively, while the mean dose of infliximab increased by 36%. There were no statistical differences between treatments in terms of clinical effectiveness. The hazard of dose escalation was significantly higher for either adalimumab (4.4-fold) or infliximab (11.8-fold) compared to etanercept (p<0.05). Clinical control was achieved and maintained in more than half of the patients treated with reduced doses of etanercept. Associated mean patient-year costs were significantly higher in adalimumab patients (€11.962.58) (etanercept €9.594.73; infliximab €10.094.53; [p<0.05]).
CONCLUSIONS: In rheumatoid arthritis patients, it is possible to reduce doses and associated costs of biological therapies while controlling disease activity. Mean doses used in our clinical practice were significantly lower with etanercept than with the anti-TNF monoclonal antibodies, adalimumab and infliximab. Dose differences impact directly on associated patient-year costs, and thus on treatment efficiency.
INTRODUCTION: Dose escalation with tumor necrosis factor (TNF)-blockers is poorly characterized in pharmacy benefit management (PBM) settings.
METHODS: This retrospective study used integrated pharmacy and medical claims from the PBM Medco to characterize dose escalation among rheumatoid arthritis (RA) patients treated with etanercept and adalimumab. Data from adults with RA with pharmacy claims for etanercept or adalimumab between 1/1/2007 and 12/31/2009 and continuous enrollment for ≥ 6 months before and ≥ 12 months after first (index) pharmacy claim were analyzed. "New" patients had no claim for TNF-blocker in the 6 months prior to receipt of their index TNF-blocker; otherwise, they were classified as "continuing" patients. Endpoints included 12-month persistence and duration on index medication and dose escalation. Dose escalation (allowed per adalimumab label but not for etanercept) in patients' persistent ≥ 12 months was estimated using five methods: (1) average weekly dose ≥ 110% of recommended label dose; (2) average subsequent dose ≥ 130% of starting dose; (3) last dose ≥ 110% of starting dose; (4) ≥ 2 consecutive instances of dose ≥ 130% of starting dose; and (5) any instance where dose increase connoted an additional syringe/vial use.
RESULTS: Data from 1,260 patients on etanercept and 852 patients on adalimumab were analyzed; 45.3 and 45.9% of new patients on etanercept and adalimumab, respectively, and 60.5 and 60.8% of continuing patients had ≥ 12 months persistence on index medication. Across all five methods used to estimate dose escalation, patients receiving etanercept had significantly lower rates of dose escalation (P < 0.001) than patients receiving adalimumab. For new patients, rates of dose escalation were 0.4-1.2% for etanercept and 8.3-14.1% for adalimumab. For continuing patients, rates ranged from 1.1 to 2.9% for etanercept and 7.0-28.3% for adalimumab.
CONCLUSIONS: New and continuing patients from this PBM database on etanercept had significantly lower rates of dose escalation than patients on adalimumab.
BACKGROUND: According to prescribing information for rheumatoid arthritis (RA) treatments in the United States, infliximab should be administered at weeks 1, 2, 6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to 10 mg/kg and/or every 4 weeks based on clinical response.
OBJECTIVE: This study evaluated dosing and intervals of the first 12 infliximab infusions in patients with RA across multiple large administrative databases.
METHODS: Data were obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database (PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged ≥18 years, diagnosed with RA, and naive to biologic therapy. Patients with other select inflammatory conditions were excluded. The induction period included infusions 1 through 3; the maintenance period included infusions 4 through 12.
RESULTS: Observed dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8, and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3, 45.7, and 45.7 mg, respectively) to the highest dose during the first 12 infusions. The mean number of days between infusions in the maintenance period ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in PPD, and 52.3 to 55.0 in the WKPS database.
CONCLUSION: Data from multiple databases of patients with RA suggest that, in clinical practice, infliximab dosing and intervals are consistent with FDA prescribing information and remain relatively stable during the first 12 infusions.
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain.
OBJECTIVE: To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9-15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation.
METHODS: This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9-15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab).
RESULTS: HAQ-DI change scores at 9-15 months did not differ by treatment (-0.12, -0.10, and -0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001).
CONCLUSIONS: Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.
OBJECTIVE: This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab.
METHODS: Non-elderly adult (age 18-65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose.
RESULTS: A total of 2747 patients met the inclusion criteria (mean age 50 years [SD=10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8-1.5% for etanercept, 10.8-12.5% for adalimumab, and 16.4-42.5% for infliximab; ranges at 24 months were 0.8-2.1% for etanercept, 14.3-17.5% for adalimumab, and 26.4-57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p<0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions.
CONCLUSION: Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.
OBJECTIVE: This study aims to provide a description of real life treatment patterns of biologic anti-TNF in 23 Italian Rheumatology centers.
METHODS: This was an observational, multicenter, retrospective study. Patients >18 years of age, diagnosed with rheumatoid arthritis and treated with the first biologic anti-TNF agent between the 1st July 2002 to the 31st March 2004 were included. Total follow-up was 36 months.
RESULTS: In total, 248 patients were first treated with infliximab, 259 with etanercept and 196 with adalimumab. First course of therapy with infliximab was associated with lower cumulative drug survival than the other two agents. At 36 months, 74.7% of patients on etanercept, 72.0% of those on adalimumab and 57.7% of subjects receiving infliximab were still on therapy. In total, 149 patients switched to a second anti-TNF agent. At 24 months of the second line treatment, 75%, 22%, and 54% of infliximab, etanercept and adalimumab recipients, respectively, had discontinued their second anti-TNF.
CONCLUSIONS: Anti-TNF agents may be associated to a rather high incidence of discontinuation and dose adjustments over a 36-month period, with a possible effect on healthcare expense. In particular, infliximab was associated with a higher incidence of discontinuations compared with etanercept and adalimumab.
OBJECTIVES: To evaluate prevalence of dose escalation among RA patients in normal clinical practice treated with etanercept, adalimumab or infliximab and to estimate its economic impact.
METHODS: A retrospective observational study of 739 patients with RA receiving continuous treatment with etanercept (n=319), adalimumab (n=313) or infliximab (n=107) for 18 months. Dose escalation, intensification of concomitant DMARDs and risk of dose escalation were evaluated, as well as costs.
RESULTS: Significantly more patients prescribed adalimumab (10%, p<0.001) or infliximab (35%, p<0.001) experienced dose escalation compared with patients treated with etanercept (3%). DMARD or steroid dose adjustment, when added as criteria of escalation, occurred more often among patients treated with adalimumab (28%; p=0.022) or infliximab (47%; p<0.001) than those prescribed etanercept (19%). Independent of confounding covariates, hazard of dose escalation was significantly higher for either infliximab (28.1-fold) or adalimumab (4.9-fold) relative to etanercept. Escalation among subjects treated with either infliximab or adalimumab incurred statistically significant increases in total cost of care compared with non-escalators whereas such differences observed for subjects treated with etanercept were not significant.
CONCLUSIONS: Patients receiving monoclonal antibody therapies, adalimumab or infliximab, had significantly higher rates of dose escalation than patients receiving the soluble TNF receptor, etanercept, and related costs were higher.
OBJECTIVES: Tumor necrosis factor (TNF) antagonists, most frequently prescribed biologics for moderate to severe rheumatoid arthritis (RA), are subject to dose escalation. Even though different methods have been employed to estimate the timing and magnitude of dose escalation, there is no consensus on which method is optimal. The purpose was to evaluate different methods for assessing dose escalation patterns for the subcutaneously delivered TNF antagonists, etanercept and adalimumab.
METHODS: Five different methods to describe dose escalation patterns were compared using a large administrative claims database from US health plans. RA patients age 18 and above with >or=2 claims for etanercept or adalimumab were included. These methods included last dose versus index dose (the dose of a patient's first biologic prescription [adalimumab or etanercept]), average dose versus recommended dose, multiple (>or=2) instances of subsequent doses exceeding the index dose, subsequent doses exceeding a predetermined threshold above the index dose, and the time-trend method, comparing each subsequent dose throughout the course of therapy to the index dose.
RESULTS: A total of 1369 etanercept and 461 adalimumab RA patients were evaluated for dose escalation. Estimates of dose escalation were highest for both drugs based on the average dose method (10.3% for etanercept, 33.6% for adalimumab). The time-trend method demonstrated the temporal trends in the percent of patients with dose escalation. Adalimumab patients had a higher rate of dose escalation than etanercept patients, regardless of method. The study is limited in that it could not assess the reason for or clinical outcomes associated with dose escalation.
CONCLUSIONS: Different methods for evaluating dose escalation yield different numerical estimates but consistently give the same overall comparative result. The choice of method should depend on the specific research question. The average dose method may be the most useful for cost impact studies, whereas the time-trend method provides the most comprehensive information on dose patterns.
This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.
METHODS:
This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005-2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose > recommended label dose, (2) average ending dispensed dose > maintenance dose, and (3) average dose after maintenance dose > maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.
RESULTS:
Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional dose escalation rates and magnitudes of escalation were directionally consistent with national rates. Etanercept had the lowest cost per treated RA patient ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030).
LIMITATIONS:
Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ∼50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.
CONCLUSIONS:
In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.
