Published Online: July 14, 2011
Anthony M. Louder, PhD, RPh; Ashish V. Joshi, PhD; Amy T. Ball, PharmD; Joseph C. Cappelleri, PhD; Michael C. Deminski, MS, RPh; and Robert J. Sanchez, PhD
Objective: To compare the incidence of serious gastrointestinal (GI) complications and associated medical costs in a population with either osteoarthritis (OA) or rheumatoid arthritis (RA) enrolled in Medicare plans with celecoxib formulary restrictions versus plans without such restrictions.
Methods: This study was a retrospective cohort analysis of Medicare members in plans with and without celecoxib restrictions. Members diagnosed with OA or RA were identified and followed for 1 year.
Results: The restricted group had higher levels of nonselective nonsteroidal anti-inflammatory drug use (51% vs 40%; P <.001), and celecoxib use was double in the unrestricted group (16% vs 8%; P <.001). The incidence of a serious GI complication was slightly higher in the restricted group (5.4% vs 4.6%; P <.001). The adjusted mean serious GI complication–related cost for the restricted group was more than 15 times higher than that for the nonrestricted group ($1559 [95% confidence interval (CI) $1341-$1811] vs $101 [95% CI $87-$117]); adjusted mean arthritis-related medical costs were $5733 per year (95% CI $5097-$6448) for the restricted group and $3170 (95% CI $2816-$3569) for the unrestricted group.
Conclusions: The restricted group had significantly less use of celecoxib, indicating that restriction was effective at reducing celecoxib utilization. Although limitations exist when comparing populations from different health plans, and the underlying causes of serious GI complications are multifactorial, the restricted group had a higher
incidence of serious GI complications and higher costs related to serious GI complications and arthritis.
(Am J Manag Care. 2011;17(7):503-512)
This study compared the incidence of serious gastrointestinal (GI) complications and associated GI- and arthritis-related medical costs between Medicare plans with and without formulary restriction policies for celecoxib.
Plans with a formulary restriction policy had a significantly higher incidence of serious GI complications.
Plans with a formulary restriction policy had significantly higher serious GI-related medical costs.
Plans with a formulary restriction policy had significantly higher arthritis-related medical costs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA).1-3 The most common adverse events experienced by NSAID users are gastrointestinal (GI) related. Adverse GI events can range from very minor dyspepsia to life-threatening GI bleeding or perforation.4,5 The major risk factors for GI complications related to NSAID use include history of GI bleed, concomitant use of anticoagulants, use of 2 or more NSAIDs, history of peptic ulcer, high-dose NSAID, age >60 years, severe illness, Helicobacter pylori infection, and concomitant use of corticosteroids.6 Lanas et al indicated that individuals over the age of 75 years are considered to be at high risk and their risk equals that of persons with a history of peptic ulcer disease.7 It has been estimated that more than 90% of all NSAIDs prescribed are for individuals over the age of 65 years.6 It is well documented that the elderly experience significant and serious GI complications with NSAIDs.7,8
Celecoxib, a selective cyclo-oxygenase (COX-2) inhibitor NSAID, has been shown to be as effective as traditional nonselective NSAIDs (nsNSAIDs), 9 although the product labeling for all NSAIDs carries the same GI and cardiovascular warning. The majority of traditional nsNSAIDs have generic equivalents available, while there are no COX-2 generic equivalents. Many health plans, in an effort to control costs, have implemented utilization management techniques such as tier placement, prior authorization, or step therapy to decrease utilization of COX-2 agents.10-12 In 2004, Briesacher et al found that members in a 3-tier pharmacy benefit design with arthritis and serious GI comorbidity were less likely to use a COX-2 agent compared with those with a 1-tier pharmacy benefit.13 Johnson et al evaluated the impact of NSAID formulary restriction on medical costs.14 They showed that the more restrictive formularies led to higher hospitalizations for OA and RA members and higher total healthcare costs for RA members.14 Although these approaches have the ability to lower pharmacy costs by decreasing utilization, very little has been published to show the impact of the restrictions on medical outcomes. Since 2007, some Medicare Advantage and Prescription Drug Plans have used various formulary management strategies to restrict the use of celecoxib. Humana health plans have used a step-therapy policy with prior authorization restriction. That is, in order to get celecoxib covered through their prescription benefit, Humana Medicare members must have tried and failed with 2 prescription-strength nsNSAIDs on the preferred drug list in the previous 6 months or must satisfy at least 1 of the following secondary criteria: currently on a prescription-strength GI medication, anticoagulant or antiplatelet therapy, bisphosphonate, chronic oral corticosteroid, or antineoplastic agent. If neither of these criteria are satisfied, the member’s provider could file a prior authorization request.
The purpose of this study was to compare the incidence of serious GI complications and associated medical costs in an elderly Medicare population with OA and/or RA enrolled in plans with restrictions on celecoxib versus plans without restrictions on celecoxib.
This retrospective study used a cohort design to identify and track members with arthritis who were covered under a Medicare Advantage or Medicare Supplemental plan. Two groups were identified for comparison: (1) restricted celecoxib coverage and (2) unrestricted celecoxib coverage. The study design was approved by an institutional review board.
All members with coverage through a Medicare Advantage or Medicare Supplemental health benefit plan who were continuously enrolled during an observation period 365 days prior to and after the index date and who were between 65 and 90 years of age on the index date were included in the study. Members who met either of the following 2 criteria were excluded from the study: (1) diagnosis of familial adenomatous polyposis during the preindex or follow-up period (defined as International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 211.3 in any diagnosis field on a medical claim) or (2) diagnosis of ankylosing spondylitis during the preindex or follow-up period (defined as ICD-9- CM code 720.0 in any diagnosis field on a medical claim).
The restricted celecoxib group was identified from Humana’s Medicare population using medical, pharmacy, and eligibility data. The unrestricted celecoxib group was identified using the MarketScan Medicare Supplemental and Coordination of Benefits Database from Thomson Reuters. Unrestricted status was based on participating in a plan that did not have a prior authorization/step therapy requirement for celecoxib. Thomson Medstat associates assigned the unrestricted status specific to each member for each calendar year. To assign this indication, members were first grouped by drug plan and year. Details on celecoxib coverage by plan and year were determined using Fingertip Formulary (Fingertip Formulary LLC, Glen Rock, New Jersey), Epocrates (Epocrates Inc, San Mateo, California), or the plans’ Web sites. When information was not available, the proportion of celecoxib fills relative to all drug fills was used as a proxy for restriction. Members enrolled in plans with <1.5% fills for celecoxib were tagged as restricted. Only members enrolled in a plan with an unrestricted status during their entire study period were considered for inclusion.
The study period was January 1, 2006, to December 31, 2008. Members who met all of the following criteria were included in the study: medical claim with an ICD-9-CM diagnosis code in any of the first 3 diagnosis fields for OA (715.x) or RA (714.x or v82.1) between January 1, 2007, and December 31, 2007. The service date of the first claim was defined as the index date. Those members who met the inclusion criterion were observed for 12 months prior to their index date and 12 months after their index date.
Pharmacy and medical claims with service dates that occurred during the individual subjects’ 24-month observation period were used to identify the outcomes of interest for the study. The composite primary end point of a serious GI complication was defined as a GI bleed or perforation (Table 1). Serious GI complications were further identified as upper or lower in nature. The relevant codes were selected based on published literature and expert opinion. The time until a serious GI complication was calculated as the number of days between the index date and service date on the medical claim.
Serious GI complication–related total medical per member per year (PMPY) costs during the follow-up period included the total outpatient and inpatient medical costs where the primary or secondary diagnosis code was for a serious GI complication. Arthritis-related total medical PMPY costs in the follow-up period included the total outpatient and inpatient medical costs where the primary or secondary diagnosis code was for RA or OA. Both plan-paid and member out-of-pocket costs were included in the calculation of serious GI- and arthritis-related medical costs. Gastroprotective and gastrotoxic medication utilization was evaluated using the pharmacy claims for the member. Arthritis treatment utilization was also evaluated (Table 2). An RxRisk-V score, which is an enhancement of the Chronic Disease Score,15,16 was calculated using pharmacy utilization during the 12 months prior to the index date. The unweighted version used in this analysis was calculated using a simple count of drugs in unique drug categories. The score can range from 0 to 27.17-19
Bivariate descriptive analyses were conducted on all study variables. The t test or Wilcoxon rank-sum methods were utilized for comparing continuous variables, and X2 tests were utilized for the categorical variables. The baseline characteristics (demographic, clinical, and drug utilization patterns) were compared between the celecoxib-restricted and celecoxibunrestricted groups. Statistical significance was set at P <.05.
Cox proportional hazard models were used to compare the restricted and unrestricted groups on the risk of serious GI complications. Time until a serious GI complication was the dependent (outcome) variable used in the model. The independent (predictor) variables used in the model were age, sex, region, OA/RA, use of medications or clinical conditions that increase risk of GI complications, and use of gastroprotective medications. Members were censored if they did not have a serious GI complication by the end of their follow-up period. Collinearity among the covariates was assessed, and based on the results there were no significant correlations between the covariates. Time-dependent covariates were included in the models to assess the proportional hazards assumption.
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