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Characteristics of Patients with Psoriatic Arthritis Receiving Secukinumab and Reasons for Initiation: A US Retrospective Medical Chart Review

Introduction Secukinumab is a fully human anti-interleukin 17A monoclonal antibody approved for the treatment of psoriatic arthritis (PsA) in the United States. Few studies have investigated prescribing patterns among rheumatologists who have initiated secukinumab for the treatment of patients with PsA in real-world settings. This US medical chart review describes clinical and treatment characteristics of patients with psoriatic arthritis (PsA) who were prescribed secukinumab and rheumatologist-reported reasons for prescribing secukinumab in clinical practice. Methods This US medical chart review included patients with physician-diagnosed PsA aged ≥ 18 years initiating secukinumab after January 15, 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, comorbidity profiles, and treatment histories before or on the date of the first secukinumab prescription recorded in the medical chart. Information on reasons for secukinumab prescription and dosing was also collected. Results Medical charts from 153 patients with PsA who initiated secukinumab were reviewed by 46 rheumatologists between July 7, 2017, and August 11, 2017. Overall, 53.6% of patients were male, mean (standard deviation) age was 47.3 (11.5) years, and 24.8% were biologic naive. The most common reasons for secukinumab prescription among biologic-naive and biologic-experienced patients, respectively, were efficacy/effectiveness of secukinumab (84.2%) and failure of other prior biologics (80.9%). Nearly all patients (94.1%) received a loading regimen, including 150 mg every week (32.7%) and 300 mg every week (61.4%). Overall, 145 patients (94.8%) received ≥ 1 maintenance dose, of whom 49.7% received 150 mg every 4 weeks and 50.3% received 300 mg every 4 weeks. Conclusions At the time of the chart review, most patients with PsA who initiated secukinumab were biologic experienced, although one-quarter received secukinumab as first-line biologic therapy. Efficacy/effectiveness of secukinumab and failure of other biologics were the most common reasons for initiating secukinumab. Funding Novartis Pharmaceuticals Corporation, East Hanover, NJ. Plain Language Summary Plain language summary available for this article.


INTRODUCTION
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis involving the skin and musculoskeletal system that affects approximately 6-41% of patients with psoriasis, with an estimated prevalence of 0.25% in the United States [1,2]. PsA is a heterogenous condition associated with nail and skin changes, peripheral joint inflammation, enthesitis, dactylitis, and/ or axial involvement, along with additional comorbidities that impact clinical burden and complicate disease management [3,4].
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR) have developed guidelines for the treatment and management of patients with PsA [5,6]. The goals of therapy for all patients with PsA are to achieve the lowest possible level of disease activity in all domains of disease (peripheral arthritis, spondylitis/axial disease, enthesitis, dactylitis, skin disease, nail disease); to optimize functional status, improve quality of life and well-being, and prevent structural damage to the greatest extent possible; and to avoid or minimize complications, both from untreated active disease and from therapy [5]. For patients with moderate-to-severe PsA, or for patients whose disease remains active despite traditional therapies, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic therapies, or targeted synthetic DMARDs are recommended. Switching biologic therapies can be an effective strategy for many patients whose disease does not respond to their initial biologic; however, switching to therapies with different mechanisms of action may be associated with better outcomes than cycling between therapies within the same class [e.g., subsequent lines of tumor necrosis factor inhibitors (TNFis)], but more research is needed to compare these responses [7,8]. Therapies with novel mechanisms of action provide patients and physicians with additional options for managing the disease. Indeed, the biologic landscape for the treatment of PsA has seen tremendous growth since early 2013, when only TNFis were available in the United States. Within the last 5 years, several non-TNFi biologics and targeted synthetic DMARDs have been approved by the US Food and Drug Administration for the treatment of PsA, including monoclonal antibodies targeting interleukin (IL) 12/23 [9,10] and IL-17A [11][12][13][14], a selective T cell costimulation modulator [15,16], an oral phosphodiesterase 4 inhibitor [17][18][19], and an oral Janus kinase inhibitor [20,21].
Secukinumab is a fully human anti-IL-17A monoclonal antibody, and in January 2016, it became the first IL-17A inhibitor approved for the treatment of PsA in the United States. Studies examining physicians' reasons for why or how a treatment is prescribed would make available valuable information to help navigate complex treatment algorithms or decision trees. However, a limited number of studies have investigated prescribing patterns among rheumatologists who have initiated secukinumab for the treatment of patients with PsA in real-world settings.
The objectives of this descriptive analysis were to characterize clinical and treatment profiles of patients with PsA who were prescribed secukinumab treatment in US clinical practice and to evaluate rheumatologist-reported reasons for prescribing secukinumab.

Data Source and Study Design
This was a retrospective medical chart review of patients in the United States diagnosed with PsA aged C 18 years who initiated secukinumab after its approval date, January 15, 2016. Rheumatologists from an existing physician panel across various practice settings and regions in the United States were screened on the basis of the following eligibility criteria: (1) completed their residency and fellowship training, (2) treated C 1 patient with PsA in the past 12 months prior to the chart review, and (3) had prescribed secukinumab for the treatment of PsA. Eligible rheumatologists were then invited to provide patient information using an online chart abstraction form.
This study was designed and implemented in accordance with the Guidelines for Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, and the ethical principles laid down in the Declaration of Helsinki [22,23]. An institutional review board exemption was obtained for the study prior to initiation of data collection.

Study Population
Eligible patients were required to meet the following criteria: (1) physician diagnosis of PsA; (2) prescription of secukinumab for the treatment of PsA by participating rheumatologists in a real-world setting (i.e., outside an interventional clinical trial) on or after January 15, 2016; (3) age C 18 years at the time of secukinumab initiation; and (4) medical records containing information on PsA diagnosis, comorbidities, and treatment history prior to the secukinumab initiation that were accessible to the participating rheumatologists.

Measures and Outcomes
The chart abstraction form was used to collect patient-level information extracted by rheumatologists from eligible patients' medical charts, such as demographics (age, sex, race, and insurance type), disease characteristics (disease duration, physician-assessed disease severity, PsA symptoms experienced, and comorbidities), treatment history (previous treatments and reasons for discontinuation of treatment immediately preceding secukinumab), and characteristics of secukinumab use [duration of treatment, dosing, current secukinumab treatment status, rheumatologist-reported reasons for secukinumab prescription, and reasons for secukinumab discontinuation (if applicable)].

Data Analysis
Descriptive analyses were conducted for all patient demographics, disease characteristics, treatment history, and characteristics of secukinumab use, as well as for physician-level characteristics. Rheumatologist-reported reasons for secukinumab prescription were also described for patients stratified by use of prior biologics. Categorical variables were summarized using frequency counts and percentages. Continuous variables were summarized by means and standard deviations (SDs) or medians and interquartile ranges. All data analyses were conducted using SAS, version 9.4 (SAS Institute).

Rheumatologist Characteristics
Medical charts from 153 patients with PsA who initiated secukinumab were reviewed by 46 rheumatologists between July 7, 2017, and August 11, 2017. Participating rheumatologists contributed a mean (SD) of 3.3 (1.6) PsA patient medical charts to the analysis. Characteristics of the participating rheumatologists are presented in Table 1. Overall, the rheumatologists had been in practice for a mean (SD) of 14.2 (9.5) years; 73.9% were from a private practice setting, and 41.3% were from the Northeast region of the United States. Most rheumatologists (78.3%) referenced published international treatment guidelines to assist with PsA diagnosis (i.e., GRAPPA and/or EULAR).

Patient Demographic and Disease Characteristics at the Time of Secukinumab Initiation
Among the 153 patients with PsA whose charts were reviewed, 53.6% were male, and the mean (SD) age was 47.3 (11.5) years (Table 2). At the time of secukinumab initiation, 15.0% of patients had a disease duration of [ 10 years, and 28.1% of patients had severe rheumatologist-assessed PsA disease severity. The most   Inflammatory eye disease 6 (3.9) PsA psoriatic arthritis; SD standard deviation a Multiple PsA symptoms could be selected for each patient except when ' 'none of the above' ' was selected b Other symptoms included ' 'impaired activities of daily living and job performance (carpenter),'' ' 'could not hold eating utensils because of arthritis,' ' and ' 'impaired activities of daily living (works as a chef).' ' secukinumab were any biologics (65.3%), conventional synthetic DMARDs (43.1%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (33.3%). The most common reasons for discontinuation of treatment directly preceding secukinumab initiation were lack/loss of efficacy/effectiveness (70.8%), disease progression (34.7%), and availability of new treatment (18.1%) (Fig. 1a).

Rheumatologist-Reported Reasons for Prescription of Secukinumab and Characteristics of Secukinumab Use
The most common rheumatologist-reported reasons for secukinumab prescription included efficacy/effectiveness of secukinumab (74.5%), failure of other prior biologics (60.8%), and newly available agent with a new mechanism of action (34.0%) (Fig. 1b). When patients were stratified by use of prior biologics, efficacy/effectiveness of secukinumab (84.2%) remained the most common reason for secukinumab prescription among biologic-naive patients, followed by newly available agent with a new mechanism of action (36.8%), and favorable safety profile of secukinumab (31.6%). Failure of other prior biologics (80.9%) and efficacy/effectiveness of secukinumab (71.3%) were the most common reasons for secukinumab prescription among biologic-experienced patients (Fig. 1c).
At the time of chart abstraction, patients had received secukinumab for a mean (SD) duration of 5.9 (4.6) months (Table 5). Nearly one-third of patients with PsA (32.7%) received a loading regimen using a dose of 150 mg every week, while 61.4% received a loading regimen using a dose of 300 mg every week, and 5.9% did not receive a loading regimen. Of the 145 patients who received an initial maintenance dose, approximately one-half (49.7%) received an initial maintenance dose of 150 mg every 4 weeks, while the remaining 50.3% received an initial maintenance dose of 300 mg every 4 weeks. The majority of patients (90.2%) were still receiving secukinumab at the time of chart abstraction, while nine patients (5.9%) had discontinued treatment, and six patients (3.9%) had an unknown treatment status. Of the nine patients who discontinued treatment, reasons for discontinuation included lack/loss of efficacy/effectiveness (n = 5), intolerance to the treatment (n = 2), adverse events from the treatment (n = 2), and worsening or new comorbid condition (n = 1).

DISCUSSION
In this medical chart review of patients with PsA who initiated secukinumab in clinical practice, nearly all patients had moderate or severe rheumatologist-reported PsA disease severity, and psoriasis was the most common comorbid condition noted at the time of secukinumab initiation, reported in approximately 40% of  [13,14]. Although there were no such tender or swollen joint requirements for inclusion in the current study, [ 90% of patients included in the chart review reported joint pain and swelling, which may be a surrogate for increased tender and swollen joint counts.
In the phase III randomized controlled trials, approximately 65-70% of patients were TNFinaive, which differed from our chart review, in which one-quarter of patients were biologic naive at the time of secukinumab initiation [13,14,24]. Additionally, the rates of enthesitis and dactylitis in our study (46.4 and 37.3%, respectively) were on the lower end of what was reported in randomized controlled trials (range 46.0-64.1% and 36.9-56.0%, respectively), possibly due to the lack of evaluation by rheumatologists or the lack of a washout period in real-world studies that is typically carried out in clinical trial settings. Despite similarities in patient characteristics between populations in clinical trials and in real-world clinical practice, comparison of disease severity across both treatment settings may be challenging due to data availability and differences in inclusion criteria. Patients enrolled in clinical trials are rigorously monitored and often have regular clinical visits in accordance with study protocols, whereas patients treated in real-world clinical practice settings may have fewer visits or visits at irregular intervals. In addition, clinical trial populations often do not represent real-world heterogeneity with regard to features such as ethnicity, age, differences in disease severity, and comorbidities. Accordingly, data obtained from real-world studies may provide insight into characteristics of more diverse patient populations.
Our study also provides information on characteristics of the rheumatologists who prescribed secukinumab to patients with PsA in clinical practice based on a short screening section of the chart abstraction form. There are limited data describing rheumatologists who treat patients with PsA in the United States, let alone data focusing only on rheumatologists who have experience with secukinumab [25,26]. The rheumatologists participating in this chart review were primarily from private practice, with approximately 15 years of experience treating PsA.
The most common prescriber reasons for initiating secukinumab among patients with PsA in this study were its efficacy/effectiveness, failure of other biologics, and its status as a newly available agent with a new mechanism of action. Because PsA is a heterogenous disease that can affect one or more domains of disease (i.e., peripheral arthritis, spondylitis/axial disease, enthesitis, dactylitis, skin disease, and nail disease), it is important to consider the efficacy/effectiveness of the treatment agents in the disease domains affecting the patient. Rheumatologists in our study may have considered prescribing secukinumab because there are high proportions of patients in this study with symptoms reflecting impairment in different disease domains, and secukinumab has shown efficacy across all PsA disease domains [13,14,24,27]. For instance, a diagnosis of moderate or severe psoriasis was reported as a prescriber reason for initiating secukinumab in approximately 14% of patients in this study. Additionally, more than 90% of patients included in the medical chart review had rheumatologist-assessed moderate or severe PsA disease severity, which may have contributed to the use of secukinumab earlier in treatment for some patients.  DMARD disease-modifying antirheumatic drug; NSAID nonsteroidal anti-inflammatory drug; PsA psoriatic arthritis; SD standard deviation a Among patients who had received C 1 treatment prior to secukinumab (n = 144). The number of all previous distinct treatments was considered, regardless of treatment combinations b Multiple treatments directly preceding secukinumab could be selected for each patient As with any retrospective chart review study, there are limitations of the study that should be considered when interpreting the results. The sample size was relatively small, which may preclude generalizability of the findings to larger patient populations in the United States; however, all regions of the United States were well represented by participating rheumatologists. Because of the small sample size, characteristics or events with a low prevalence may also not be estimated reliably. At the time of chart abstraction, approximately 90% of patients who initiated secukinumab had remained on therapy, but further longitudinal investigation is needed to document patient experiences and treatment outcomes. This study might have been affected by nonrandom missing data from the medical charts; for example, although information about comorbidities was collected by the chart review, the level of detail in the documentation may not have been consistent across medical charts. In addition, validated instruments that assess quantifiable measures of disease severity [e.g., the Composite Psoriatic Disease Activity Index (CPDAI), the Disease Activity Index for Psoriatic Arthritis (DAPSA), or achievement of minimal disease activity (MDA)] [28][29][30] or severity of patient-reported outcomes (e.g., the Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire] [31,32], which are more relevant for clinical trials, are not often captured in clinical practice and are not reported in medical charts. Instead, assessments of disease severity and treatment effectiveness in realworld settings may be based on heterogeneous criteria from clinical opinion. Although our study captured the proportion of patients who experienced symptoms associated with PsA disease domains, additional studies with larger sample sizes that provide clarity on the number, type, and severity of disease domains affected in patients with PsA would help rheumatologists better understand which aspects of disease are most common among those patients treated with secukinumab. Finally, the choice of biologic and the decision of when to use secukinumab might have differed on the basis of the formulary of each payer/employer group.

CONCLUSIONS
Findings from this retrospective medical chart review provide information on the characteristics of patients with PsA who initiated secukinumab in US clinical practice. Most patients with PsA who initiated secukinumab were biologic experienced and had moderateto-severe rheumatologist-reported PsA; efficacy/effectiveness of secukinumab, failure of other biologics, and desire to initiate a newly available agent with a new mechanism of action were the most common reasons for initiating secukinumab. These findings are among the first data to highlight characteristics of patients with PsA who initiate secukinumab in realworld clinical practice and may help inform treatment decisions for rheumatologists.
Medical Writing and Editorial Assistance. Support for third-party writing assistance, furnished by Eric Deutsch, PhD, CMPP, of Health Interactions, Inc, was provided by Novartis Pharmaceuticals Corporation, East Hanover, NJ.
Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all of the data in this study, take complete responsibility for the integrity of the data and accuracy of the data analysis, and have given their approval for this version to be published.

Disclosures. Prashanth
Sunkureddi has received speakers bureau fees from Novartis and is an investigator of a clinical trial sponsored by Novartis Pharmaceuticals Corporation. Dominick Latremouille-Viau is an employee of Analysis Group, Inc. Mark K. Meiselbach is an employee of Analysis Group, Inc. Jipan Xie is an employee of Analysis Group, Inc. Peter Hur is an employee of Novartis Pharmaceuticals Corporation. Reeti Joshi has received consulting fees from Novartis Pharmaceuticals Corporation.
Compliance with Ethics Guidelines. This study was designed and implemented in accordance with the Guidelines for Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, and the ethical principles laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards [22,23]. An institutional review board exemption was obtained for the study prior to initiation of data collection.
Data Availability. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open Access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/ by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.