Real-World Dosing and Utilization of Ustekinumab Among Patients With Psoriasis
Published Online: June 20, 2014
Qian Cai, MS, MSPH; Chureen Carter, PharmD, MS; Azza AbuDagga, PhD, MHA; Brad Schenkel, MS; Megan Jones, PharmD, MPA; and Hiangkiat Tan, BPharm, MS
Psoriasis—a chronic, inflammatory skin disease affecting approximately 2.2% of the US population—is considered the most prevalent immune-mediated inflammatory disease.1,2 Approximately 80% of patients with psoriasis have mild to moderate disease, whereas the remaining 20% have moderate to severe disease.3 Mild psoriasis involves itching and burning on affected parts of the body, while severe psoriasis is also frequently associated with joint pain or arthritis.3-6 As a multisystemic disorder, psoriasis is frequently associated with a number of comorbid conditions, including psoriatic arthritis, cardiovascular disorders, hypertension, dyslipidemia, metabolic syndrome, obesity, and diabetes. 7-11 Notably, due to skin lesions, patients with psoriasis also often experience significant psychological comorbidities, such as anxiety and depression.12,13
There is no available cure for psoriasis; therefore, various lines of therapies are used to alleviate disease symptoms, reduce or clear plaques, and induce remission.14 Conventional therapies, including topical agents, phototherapy (such as psoralen plus ultraviolet A or ultraviolet B), and systemic medications (such as methotrexate, retinoids, or cyclosporine) have been used as the mainstay treatments of psoriasis. However, previous studies have shown that, for some patients, these therapies may be limited in the long term due to adverse events (AEs).3,15,16 With the increased understanding of the immunology of psoriasis, biologics have emerged as an alternative option with significant impact on providing long-term continuous psoriasis control by interfering with T cell function, by inhibiting tumor necrosis factor-α, or by selectively targeting interleukin-12 (IL-12) and IL-23.3,16,17 The American Academy of Dermatology (AAD) guidelines recommend biologics in the management of psoriasis when 1 or more conventional systemic medications are not tolerated due to AEs, are unsuitable due to comorbidities, or fail to produce an adequate response.3,16 Furthermore, the most recent AAD guidelines emphasize that biologics have no relevant drug interactions and have fewer significant safety issues compared with conventional systemic agents; they also highlight the benefits of biologic treatments for patients with complex medical and dermatologic histories on various medications.16
Ustekinumab, as the first agent to inhibit IL-12/23, is a novel biologic. It was approved by the FDA in September 2009 for the treatment of moderate to severe psoriasis,18 and has also been recently recommended as a first-line systemic treatment specifically for patients with chronic plaque psoriasis.16,19 The dose of ustekinumab is determined on the basis of patient weight. For patients weighing 100 kg (220 lb) or less, the recommended dose is 1 initial 45-mg dose followed by another dose 4 weeks later, then another 45-mg dose every 12 weeks thereafter. For patients weighing more than 100 kg (220 lb), the recommended dose is 1 initial 90-mg dose followed by another dose 4 weeks later, then a 90-mg dose every 12 weeks thereafter. It is worth noting that 45-mg ustekinumab was also shown to be efficacious in patients weighing more than 100 kg; however, 90-mg ustekinumab resulted in greater efficacy in these patients.18 Clinical trials have demonstrated the safety and efficacy of ustekinumab in improving the symptoms of psoriasis.20-23 Recently published 5-year efficacy and safety results demonstrate the long-term response associated with ustekinumab as well as the lack of any dose-related or cumulative toxicity with increasing duration of ustekinumab exposure for up to 5 years.24,25 Additionally, results from a phase 3, doubleblind trial have shown that the efficacy of ustekinumab was superior to that of etanercept in patients with psoriasis. 26,27 Despite these positive findings on the efficacy and safety of ustekinumab in clinical trials, limited studies are available to quantify the real-world utilization and dosage patterns of ustekinumab. The main objective of this study was to assess the characteristics and dosing patterns of patients with psoriasis initiated on ustekinumab therapy using a large retrospective administrative claims database.
This retrospective analysis used patient-level data from the HealthCore Integrated Research Database (HIRD, HealthCore Inc, Wilmington, DE). HIRD includes longitudinal claims data from 14 geographically dispersed health plans in the United States, covering approximately 44 million insured lives at the time this study was conducted. HIRD consists of integrated medical claims, pharmacy claims, and eligibility files. All study data were de-identified and developed in compliance with the Health Insurance Portability and Accountability Act. It was determined that a waiver of informed consent from an institutional review board was not required to conduct this study.
The study population consisted of patients 18 years or older who received ustekinumab and had at least 1 medical claim for psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9- CM] code of 696.1x) during the study period of September 1, 2009, through November 30, 2010. Ustekinumab was identified from medical claims using the Healthcare Common Procedure Coding System code C9261, or any of the following National Drug Codes ([NDCs]: 57894006002, 57894006003, 57894006103) from pharmacy claims. The date of the first medical or pharmacy claim for ustekinumab was designated as the index date.
All patients included in the analysis were required to have at least 12 months of continuous health plan enrollment prior to the index date. Due to the recent availability of ustekinumab and its early uptake at the time of the study, limited follow-up data were available for the study patients. Therefore, no minimum follow-up period was required and variable follow-up was allowed; however, patients were followed through the latest date of their continuous eligibility after the index date. Patients were excluded from the study if they had a claim for another biologic (ie, adalimumab, alefacept, etanercept, or infliximab) on the index date (Appendix).
Patient Characteristics. Patient characteristics were evaluated during 12 months prior to the index date. Demographic characteristics included age, gender, geographic region (as determined by the US Census classification), and type of health insurance plan (preferred provider organization [PPO], health maintenance organization [HMO], or other insurance plan type). Patients’ comorbidity burden was measured using the Deyo-Charlson Comorbidity Index (DCI)28 and specific psoriasis-related comorbid conditions during the pre-index period. The DCI consists of 19 diagnoses identified by ICD-9-CM codes, with a scoring weight from 1 to 6 identified for each diagnosis. The final summary DCI score consists of a sum of weighted values for existing comorbidities, ranging from 0 to 33, with higher scores indicating a greater comorbidity burden. Additionally, the use of various psoriasis- related treatments during the 12-month pre-index period was assessed. Pre-index all-cause and psoriasisrelated healthcare resource utilization and costs, including inpatient admissions, emergency department (ED) visits, physician office visits, and pharmacy fills, were presented. Pre-index costs were calculated using health plan allowed amounts, which are the full fees contractually allowed by health plans (inclusive of the amount paid by the health plan and the patient), and were adjusted for 2010 dollars using the medical care consumer price index from the Bureau of Labor Statistics.29
Ustekinumab Dosing Patterns. Observing ustekinumab dosing patterns required methodological considerations as a result of how the drug was packaged and supplied after FDA approval, while accounting for typical reimbursement and practice patterns. Initially, a 45-mg ustekinumab vial could be used in patients with either dose requirement, whereby a patient requiring a 45-mg dose would be prescribed 1 vial and a patient requiring a 90-mg dose would be prescribed 2 vials. The 45-mg vial was subsequently replaced by 45-mg and 90-mg prefilled syringes (PFSs) in February 2010, allowing for more convenient administration options. Preliminary analyses conducted by the authors found that health plans would reimburse for the first 2 doses of ustekinumab in a single prescription. Indicators in the administrative claims of this type of reimbursement practice included the cost of the fill and the time interval between fills.
In determining the index ustekinumab dose, patients with a single claim of 45-mg or 90-mg PFSs were categorized as having received the 45-mg or 90-mg dose, respectively. For patients who had a second fill within 98 to 125 days (ie, 16 weeks ± 2 weeks) between the index date and the next fill date, the index dose was determined using the wholesale acquisition cost ± 15% along with the allowed cost amounts in the claims. For these patients, the second fill was coded as the third dose to account for the first claim including doses 1 and 2, and all subsequent doses were recoded forward thereafter. For all other patients, second and third doses were determined by the dose shown in the claim.
Intervals between fills were calculated as the days between observed ustekinumab fills. Interval patterns were assessed based on a window around the recommended fill intervals per prescribing information (ie, 28 ± 7 days for the interval of index to second dose, and 84 ± 14 days for interval of second and third dose). Patients were then categorized as having fills “expected,” “later than expected,” or “earlier than expected” by comparing the observed fill intervals against the FDA label-recommended fill intervals.
Statistical Analyses. Descriptive statistics were calculated for all study measures and outcomes. Mean (± SD) and median were calculated for continuous variables and frequency (percentage) was used for categorical variables. All the statistical analyses were conducted using SAS Version 9.1 (SAS Institute, Inc, Cary, North Carolina).
Of the 563 patients with at least 1 medical or pharmacy claim for ustekinumab during the study period, 374 met all study criteria and were included in the analysis (Figure 1). The mean (± SD) age was 48.0 (± 11.9) years, 43.6% were female, and 74.9% were primarily covered by PPO health insurance plans (Table 1). Approximately 70% of the study patients resided in the West and Southeast regions of the United States. On average, study patients had a 6-to-7- month follow-up period with a median of 209 follow-up days after the index fill.
At baseline, the mean DCI score was 0.6 (SD ± 0.9), indicating low burden of comorbid conditions. The most commonly occurring comorbid conditions were dyslipidemia (46.3%), hypertension (43.3%), psoriatic arthritis (22.2%), diabetes (16.3%), and anxiety (12.0%). A total of 217 patients (58.0%) used topical steroids during the pre-index period while 36.4% used non-biologic systemic medications (Table 1). Methotrexate (19.3%) and prednisone (13.1%) were the most commonly administered nonbiologic systemic medications.
In terms of healthcare resource utilization, about 9.1% of study patients had at least 1 hospital admission for any cause within the 12-month pre-index period before receiving ustekinumab (Table 1), for which the average length of stay was 4 days. A few patients (2.7%) had 1 or more psoriasis-related hospital admission, with an average length of stay of 3 days, and only 7 patients (1.9%) had 1 or more psoriasis-related ED visit during the preindex period. Within the pre-index period, study patients had an average of 10 all-cause physician office visits and 4 psoriasis-related physician office visits. During the preindex period, the average all-cause costs were $22,495 (± $19,978) and the average psoriasis-related costs were $17,560 (± $26,031), more than half of which were due to prescriptions.
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