Chureen Carter, PharmD, MS

: This retrospective study compared the treatment patterns of ustekinumab (UST), with recommended maintenance administration every 12 weeks, with adalimumab (ADA) and etanercept (ETA), administered weekly or every other week, for the treatment of plaque psoriasis.

: Persons with psoriasis ≥18 years and having ≥1 medical or pharmacy claim for UST or ≥1 pharmacy claim for ADA or ETA, from February 8, 2010, to January 31, 2011, were selected from the MarketScan databases and assigned to mutually exclusive cohorts. Patient characteristics and dose escalation were described during the 12-month pre-index period and 12-month follow-up period, respectively. Differences in baseline characteristics were adjusted using inverse probability of treatment weights. Pairwise comparisons of rates of discontinuations, restarts, and switches were made between ADA and UST and between ETA and UST.

: A total of 2933 ADA, 4011 ETA, and 583 UST patients were selected. Patients in the UST cohort had higher baseline comorbidity scores and greater exposure to multiple psoriasis drugs at baseline. Dose escalation was observed in 7.8% of ADA patients, 30.9% of ETA patients, and 18.2% of UST patients. Discontinuations were seen in 38.6% of UST patients, 53.3% of ADA patients, and 56.2% of ETA patients. Restarts were seen in 8.9% of UST patients, 17.5% of ADA patients, and 23.1% of ETA patients. Switching to a nonindex medication occurred in 14.8% of UST patients compared with 22.0% of ETA patients and in 14.4% of UST patients compared with 20.8% of ADA patients.

: Discontinuations, restarts, and switches were common for all 3 biologics, but were significantly lower among patients with psoriasis receiving UST compared with those receiving ADA or ETA.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease affecting as many as 7.4 million Americans, or 3.2%of the United States population 20 years and older.

 Plaque psoriasis is the most common form and manifests as elevated red lesions covered by scaling silvery plaques. Psoriasis affects health-related quality of life, treatments can be costly and time-consuming, and patients with more severe psoriasis experience a greater negative impact on their quality of life.

Three subcutaneously administered biologic drugs, adalimumab (ADA),

 are effective for use in the treatment of moderate to severe plaque psoriasis and improve health-related quality of life.

 ADA and ETA block the cytokine tumor necrosis factor-alpha (TNF-alpha) that is associated with inflammation.

ADA is recommended for administration as an initial 80-mg dose (induction dose) followed by 40 mg every other week starting 1 week after the initial dose (maintenance period).

 ETA is recommended for administration as a 50-mg dose twice per week for 3 months (induction period) followed by a step down to a 50-mg dose once per week (maintenance period).

UST, the most recently approved of the 3 biologics (approved September 25, 2009), selectively targets the cytokines interleukin 12 and 23 that are associated with psoriasis inflammation.

 UST is recommended to be administered at weeks 0 and 4, and then every 12 weeks thereafter. It is dosed by weight: 45 mg for patients ≤100 kg and 90 mg for patients >100 kg.

All 3 products can be administered by healthcare professionals or self-administered by patients. Adjustments to the dosing and administration schedules of ADA and ETA are necessary for those responding suboptimally to the standard dosing regimen.

Currently, few studies have been published comparing UST with the other subcutaneous biologic medications used to treat psoriasis in real-world clinical practice.

 The objectives of this study were to examine the dosing and timing of UST and to compare patient characteristics, dose escalation, discontinuation, restarts, and switching with the subcutaneous TNF-alpha inhibitors, ADA and ETA.

This retrospective analysis used the Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases, which contain administrative healthcare claims for inpatient and outpatient medical and outpatient pharmacy services. Individuals in the databases are insured through a variety of private health plans, including preferred provider organizations, indemnity plans, and health maintenance organizations.

The Medicare database contains claims for individuals insured through Medicare supplemental commercial insurance. Both Medicare-covered and insurer-covered services are included due to coordination of benefits. These databases include enrollment data from approximately 150 large employers and health plans across the United States, which provide private healthcare coverage and contain more than 60 million covered lives per year.

Data are de-identified and are fully compliant with the Health Insurance Portability and Accountability Act of 1996. As this study did not involve the collection, use, or transmittal of individually identifiable data, it did not require Institutional Review Board review or approval.

Persons who were included in the analyses were ≥18 years; had ≥1 pharmacy claim for ADA, ETA, or UST, or had ≥1 medical claim for UST, between February 8, 2010, and January 31, 2011 (index date); had at least 12 months of pre- and postindex continuous enrollment in medical and pharmacy benefits; and had at least 1 nondiagnostic claim with a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 696.1) on the index date or during the 12-month pre-index period.

Patients with a diagnosis of any of the following conditions on the index date, or during the 12-month pre-index period, were excluded: rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis. Patients were selected into 3 mutually exclusive cohorts (ADA, ETA, UST) based the index drug.

Measures Assessed During the 12-month Pre-index Period

 and individual comorbidities were assessed using the ICD-9-CM codes on nondiagnostic medical claims during the baseline period. Psoriasis treatments were also assessed during the baseline period. Per-patient healthcare expenditures were measured using paid amounts for adjudicated claims. Psoriasis-related expenditures were measured using medical claims with a diagnosis of psoriasis and pharmacy claims for any psoriasis treatment.

For UST medical claims, the dose was imputed using the amount paid on the claim and data for the wholesale acquisition cost at the time of the claim. This imputation was applied in <5% of the UST cohort. The dose for pharmacy claims was computed by multiplying drug strength (specified by the National Drug Code) by the quantity.

Dose escalation for UST was defined as the presence of any claim with a dose higher than the patient’s initial dose. For ADA and ETA, maintenance dose escalation was defined as an average weekly dose ([total dispensed dose]/[days’ supply/7]) in the maintenance period >15% higher than the maintenance dose recommended on the product label. The ADA maintenance period was defined as starting with the second ADA claim, and the ETA maintenance period was defined as the period starting 91 days after the index date.

Discontinuation was defined as a treatment gap ≥90 days after the end of the days’ supply on a pharmacy claim for ADA and ETA, which allowed for refill of a 90-day mail order pharmacy claim before a patient discontinued. For UST, discontinuation was defined as a treatment gap ≥168 days after the end of the days’ supply for pharmacy claims or the effective days’ supply for medical claims (28 days for the first claim and 84 days for subsequent claims). A treatment gap of twice the dosing interval for UST (168 days) was selected after a review of the literature.

Treatment restart was defined as the presence of a prescription or medical claim for the index medication following discontinuation of the index medication. Treatment switch was defined by the presence of a prescription claim for a nonindex biologic medication following discontinuation of the index medication.

Pairwise descriptive comparisons of demographics, comorbidities, healthcare expenditures, and psoriasis treatments in the pre-index period were made between ADA and UST and between ETA and UST. Chi-squared tests were conducted for differences in dichotomous or categorical variables, and t tests were conducted for comparisons of continuous variables.

To address potential selection bias, a propensity-score—based inverse probability of treatment weighting (IPTW) was used. IPTW was used to reduce the observed differences in the outcomes due to the drug assignment rather than other underlying differences, such as age and comorbidities.

Two logistic regression models were estimated: 1 to compute the propensity score for the choice of ADA versus UST and 1 for ETA versus UST. The variables used in the models included demographics, pre-period comorbidities and expenditures, and the counts of pre-period psoriasis treatments.

The results of these models were used to assign a weight (inverse of the propensity score) to each patient. The comparisons of the proportions of patients who discontinued, restarted, or switched were conducted using the weighted data. To further control for remaining imbalance in baseline characteristics, Cox proportional hazards models were used to estimate the hazard ratios for discontinuation comparing ADA versus UST and ETA versus UST.

There were 2933 ADA, 4011 ETA, and 583 UST patients who received a psoriasis diagnosis who met the selection criteria (Figure 1).

Pre-period Demographic and Clinical Characteristics

Patients in the UST cohort were slightly older, and there was a higher proportion of UST (10.5%) patients ≥65 years compared with ADA (7.8%; P = .033). UST patients had a higher average CCI (0.46) compared with ADA (0.35; P = .004) and ETA (0.37; P = .02).

The UST cohort had a higher proportion of patients with dyslipidemia (23.3%) compared with ADA (18.9%; P = .015) and ETA (20.2%; P = .083), and a higher proportion of patients who had been given an obesity diagnosis (6.3%) compared with ADA (3.8%; P = .004) and ETA (3.5%; P <.001). Patients in the UST cohort had significantly higher pre-period total and psoriasis-related healthcare expenditures than the ADA cohort, but expenditures were not significantly different than those of the ETA cohort (Table 1).

Most UST patients (93.1%), 78.4% of ADA patients, and 72% of ETA patients had a previous topical, systemic, or biologic treatment (P <.001 in all comparisons). Receipt of the index treatment as third-line or higher (2+ prior biologic therapies other than the index drug) was observed in 29.2% of UST patients compared with 8.5% of ADA (P <.001) and 2.4% of ETA (P <.001) patients. The UST patients were all taking UST for the first time, whereas 70.0% of the ADA patients (P <.001) and 82.3% of the ETA patients (P <.001) had taken their respective drugs during the pre-period (Table 2).

The median number of days between UST doses 1 and 2 was 28, as recommended in the drug’s label (Figure 2). The mean and median number of days between subsequent doses were slightly higher than the 84 days in the prescribing guidelines.

Overall, dose escalation was 18.2% among UST patients (Figure 3). At the second dose, only 1.3% of patients had escalated from 45 mg to 90 mg. At dose 3, 12.2% of patients who had initiated at 45 mg were taking the 90-mg dose. The proportion of escalators at doses 4, 5, and 6 were 15.5%, 16.9%, and 18.5%, respectively. Maintenance dose escalation was 7.8% among ADA patients and 30.9% among ETA patients.

IPTW Comparisons of Baseline Characteristics

The propensity models of UST versus ADA and UST versus ETA resulted in weighted cohorts that were well balanced in terms of demographics, CCI, comorbidities, and pre-period healthcare expenditures. The major differences that remained after weighting were the proportions with various types of pre-period treatments.

The weighted UST cohorts had higher proportions of patients with any pre-period biologic, systemic, or topical therapy other than the index drug (90.5% of UST vs 80.3% of ADA; P <.001; 91.6% of UST vs 74.2% of ETA; P <.001) and higher proportions of patients with prior phototherapy (9.4% of UST vs 6.4% of ADA; P = .008; 11.3% of UST vs 5.0% of ETA; P <.001).

IPTW Comparisons of Discontinuations, Restarts, and Switches

Smaller proportions of the UST cohort discontinued, restarted, or switched than in the other cohorts (P <.001 for all comparisons). Specifically, 38.6% of UST discontinued versus 53.3% of ADA, 8.9% of UST restarted versus 17.5% of ADA, and 14.4% of UST switched versus 20.8% of ADA.

Also, 38.6% of UST discontinued versus 56.2% of ETA, 8.9% of UST restarted versus 23.1% of ETA, and 14.8% of UST switched versus 22.0% ETA (Table 2). The results of the multivariate proportional hazard models indicated a lower hazard of discontinuing for UST compared with either drug. The hazard ratio of discontinuing and 95% CI for UST versus ADA was 0.626 (95% CI, 0.580-0.676) and for UST versus ETA, 0.586 (95% CI, 0.545-0.629).

This study found that prior to starting UST treatment, patients with psoriasis initiating UST treatment had higher comorbidity rates and higher baseline healthcare costs compared with patients who were initiating or continuing ADA or ETA. Also, a higher proportion of UST patients were on a third-line biologic therapy.

After using the IPTW technique to balance the baseline characteristics of the 3 cohorts, the UST cohort had the lowest rates of discontinuation, restarts, or switches during 1 year of follow-up. Cox proportional hazards models adjusted for any remaining imbalances and showed that UST patients had a significantly lower hazard of discontinuation compared with ADA or ETA patients.

Clinical studies have shown that dose escalation may improve effectiveness for those with severe disease who are inadequately or only partially responding to the standard dosing regimens of all 3 of the drugs.

 The dosing intervals of UST were consistent with the prescribing guidelines, and dose escalation occurred in 18.2% of UST patients.

 Maintenance dose escalation occurred in 7.8% of ADA patients and 30.9% of ETA patients. This study did not examine whether shortening or lengthening the interval between doses contributed to dose escalation, nor did we have clinical information to understand the reason(s) for dose escalation.

One study used a physician survey to evaluate the baseline characteristics of patients with psoriasis treated with ADA, ETA, or UST and found that UST had a higher proportion of patients with prior biologic use: 62.5% of UST 90 mg, 55.4% of UST 45 mg, 14.4% of ADA, and 25.0% of ETA.

 The highest average number of baseline comorbidities was found in the UST 90-mg group (1.6), while the UST 45-mg group (1.1) was similar to ADA (1.2) and ETA (1.1).

Several studies have examined therapy discontinuation among patients with psoriasis treated with all 3 of our study drugs, each showing that discontinuation of psoriasis treatments was common, but that discontinuation rates were lowest among UST patients.

Feldman and colleagues used administrative claims data to evaluate medication utilization patterns of first-line ADA, ETA, and UST patients.

 In that study, discontinuation rates over a 12-month follow-up period post titration were lowest for UST (16%) and higher for ADA (27%) and ETA (35%). Another study used chart data to follow psoriasis patients for 4 years.

The UST group had the lowest discontinuation rate (39%) compared with 50% for ADA and 60% for ETA. Another study using administrative claims data included 8 patients with psoriasis treated with UST, 195 treated with ADA, and 369 treated with ETA.

Also in that study, discontinuation was evaluated among new initiators and existing users, and was defined as a gap ≥45 days of therapy without a restart or switch during the year. No UST patients discontinued treatment. Discontinuation rates were higher among initiators (ADA, 31%; ETA, 33%) than among existing users (ADA, 13%; ETA, 18%). Note that in our study, all of the UST patients were initiators of UST (see Table 2), while in the weighted cohorts, 68% of ADA and 80% of ETA patients had received the index drug during the baseline year.

Articles

This retrospective study compared the treatment patterns of ustekinumab with recommended maintenance administration every 12 weeks, with adalimumab and etanercept, administered weekly or every other week, for the treatment of plaque psoriasis.

Comparative Treatment Patterns Among Psoriasis Patients Using Adalimumab, Etanercept, or Ustekinumab

Psoriasis—a chronic, inflammatory skin disease affecting approximately 2.2% of the US population&mdash;is considered the most prevalent immune-mediated inflammatory disease.

Approximately 80% of patients with psoriasis have mild to moderate disease, whereas the remaining 20% have moderate to severe disease.

Mild psoriasis involves itching and burning on affected parts of the body, while severe psoriasis is also frequently associated with joint pain or arthritis.

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. 

Notably, due to skin lesions, patients with psoriasis also often experience significant psychological comorbidities, such as anxiety and depression.

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.

 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).

 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.

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.

 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.

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,

 and has also been recently recommended as a first-line systemic treatment specifically for patients with chronic plaque psoriasis.

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.

 Clinical trials have demonstrated the safety and efficacy of ustekinumab in improving the symptoms of psoriasis.

 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.

 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. 

 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

] 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 (

. 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)

 and specific psoriasis-related comorbid conditions during the pre-index period. The DCI consists of 19 diagnoses identified by 

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.

. 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.

. 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 (

). 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 (

). 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.

The majority of study patients (69.5%) used at least 1 biologic agent prior to ustekinumab initiation. Of those with pre-index biologic experience, 22.3% had a history of using 2 or more biologics. Adalimumab and etanercept were the most frequently used biologics, with 38.8% and 40.0% of the biologic-experienced patients, respectively, using them immediately prior to initiating ustekinumab (

). In addition, the average time lapse between the last etanercept fill and the index ustekinumab fill was 77.5 days (± 74.3); similarly, the time lapse between the last adalimumab fill and the index ustekinumab fill was 76.8 days (± 85.2).

In the analysis of ustekinumab dosing patterns, all patients who met the study criteria of having 1 fill or more for ustekinumab were included. Overall, 83.8% (284 of 339 who were followed up for 4 weeks or more) of patients had a second ustekinumab fill and 87.7% (207 of 236 who were followed up for 16 weeks or more) had a third ustekinumab fill after the index fill. On the index date, most patients (n = 294, 78.6%) received a 45-mg ustekinumab dose while the remaining 80 patients (21.4%) received a 90-mg dose (

). During the postindex period, the majority of the study patients remained on the 45-mg dose of ustekinumab, although a few patients switched to a 90-mg dose. Specifically, at the time of the second fill, 8 of 284 patients (2.8%) received a higher dose and only 1 patient received a lower dose than their index dose. By the third fill, 13 of 207 patients (6.9%) received a higher ustekinumab dose, while 5 patients (2.7%) received a lower dose than their previous fill. The median number of days was 28 days between the index and the second ustekinumab fill, and 85 days between the second and the third ustekinumab fills (Table 3). These findings are very much in line with the recommended dosing regimen for ustekinumab, in that the second dose should be administered 4 weeks (28 days) after the first dose and the following doses should be administered every 12 weeks (84 days) thereafter.

Among patients with a second ustekinumab fill (n = 284), most patients (70.1%) had their second prescription filled as expected (within 21-35 days of index fill). Fewer patients (4.2%) got their second fill earlier than expected, while 25.7% had it filled later than expected (

). Among patients with a third ustekinumab fill (n = 207), 75.9% had their third prescription filled as expected (within 71-97 days from the date of the second fill), while the rest had their third filled earlier (8.7%) or later (15.4%) than expected.

This is the first study to provide real-world evidence of the demographic and clinical characteristics, as well as the treatment patterns, of patients with psoriasis who were initiated on ustekinumab. Specifically, this study described the observed dosage patterns of ustekinumab in a large managed care population in the United States.

Results from this study show that approximately 69.5% of patients used at least 1 type of biologic agent, 58.0% used topical steroids, and 36.4% used nonbiologic systemic treatments prior to ustekinumab initiation. Among those who had received other biologics prior to receiving ustekinumab, the majority (78.9%) had used etanercept or adalimumab as the most recent biologic agent, and the average time between switching from etanercept or adalimumab to ustekinumab was quite similar (about 77 days). Previous studies present mixed evidence for patients with psoriasis who were treated with systemic therapy. For example, a claims study found that only 3.1% of patients had used biologic therapy and more than 30% had used 1 type of systemic therapy.

 found that only 26% of respondents had used systemic medication, phototherapy, or both, and 35% received only topical therapy. Consistent with results from another psoriasis administrative claim—based study,

 this study found that dyslipidemia and hypertension were the 2 most prevalent comorbidities for patients with psoriasis. Diabetes, anxiety, and depression were found at baseline in more than 10% of patients in the current study.

This study found that approximately 78.6% of the patients were initiated at a 45-mg dose on the index date and the remaining patients (21.4%) received 90-mg ustekinumab. Fewer than 7% of patients had an increased dose at the third fill, in contrast to a nearly 3% of patients receiving a decreased dose at the third fill. This study also showed that most patients had their second and third prescriptions filled as expected, per the recommended dosing schedule. When ustekinumab was not filled as expected after the index fill, 50.7% and 78.1% had their second and third ustekinumab, fill, respectively, within 30 days of the recommended schedule date.

Information on treatment adherence is important because better treatment adherence has been associated with decreased healthcare resource utilization and decreased other costs for many chronic diseases such as diabetes,

 Although this study did not assess adherence or persistency of ustekinumab due to a limited sample size and follow-up time, this study demonstrated that the majority of patients had their second (83.8%) and third (87.7%) ustekinumab prescriptions filled within the expected time frame, suggesting that adherence with ustekinumab may be promising. However, this hypothesis needs to be confirmed with further research, at which time it would also be worthwhile to examine ustekinumab treatment adherence and the associated economic benefit of adherence among patients with psoriasis.

This study was subject to a few limitations inherent in analyses of retrospective claims data. The existence of a pharmacy claim for a filled prescription does not guarantee that the medication was actually used by the patient, nor does it indicate that the medication was taken as prescribed. Administrative claims data do not typically include clinical data to assist with inferring the effectiveness of a treatment (such as ustekinumab in this study). Study results were derived from a database of members of large commercial health plans in the United States; therefore, results may not be generalizable to people with other types of insurance or those who reside outside the United States. Nonetheless, the data used in this study were derived from a large, geographically diverse population, which enhances the generalizability of the results. In addition, the scope of this study was intended to represent initial ustekinumab dosing patterns, and therefore the results should not be generalized for longer-term maintenance use of the drug.

The findings from this study can offer data to health plans regarding the characteristics of patients with psoriasis who were initiated on ustekinumab. As the first study to investigate the utilization patterns of ustekinumab in a large US managed care population, this study provides insights on the real-world dosage patterns and fill intervals of ustekinumab. The majority of patients with psoriasis in this study received fills per the recommended administration schedule at the 45-mg dose with very few changes in dose following the index administration. Results on ustekinumab dosage and fill patterns have important implications in estimating the cost of ustekinumab from the perspective of healthcare payers. These results may be incorporated in health plan utilization reviews, may be used as part of indirect comparisons with existing data for other biologics, and may offer payers a path to treatment cost predictability.

This study is an evaluation of the dosing patterns of ustekinumab among patients with psoriasis in a real-world setting.