FormalPara Key Summary Points

Why carry out this study?

Psoriatic arthritis (PsA) is an immune-mediated systemic inflammatory disease and associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs have been demonstrated in patients with PsA.

There are limited real-world data on patient compliance and economic burden in a PsA population treated with tofacitinib.

This study follows up from a previously published 6-month study; here, we further describe tofacitinib adherence and persistence over a larger sample size and longer follow-up (up to 30 months) and evaluate costs and HCRU in patients with PsA who were treated with tofacitinib both as monotherapy and/or in combination with conventional synthetic disease-modifying antirheumatic drugs.

What was learned from the study?

Descriptive comparisons of data across two large US databases showed that tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy; costs (driven by numerically lower medication costs) and outpatient visits numerically decreased off-treatment vs on-treatment.

Although this study provided further understanding of tofacitinib use in a real-world setting, studies investigating patient characteristics could help to determine the main factors associated with tofacitinib economic burden and compliance.

Introduction

Psoriatic arthritis (PsA) is an immune-mediated systemic inflammatory disease with multiple disease manifestations, including peripheral arthritis, enthesitis, dactylitis, and spondylitis, together with skin and/or nail psoriasis [1]. PsA may occur in approximately 20–30% of patients with psoriasis [2,3,4], and the incidence of PsA has been reported to range from 0.27 to 2.7 per 100 person-years across two meta-analyses [4, 5]. PsA imposes a significant burden on patients, reducing quality of life by limiting their ability to carry out everyday tasks, negatively impacting work productivity, and causing frequent healthcare visits and hospitalizations and high medical expenses [3, 6]. Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs have been demonstrated in patients with PsA [7]. In a large US cohort study, the unadjusted mean direct annual healthcare costs during a 12-month follow-up period for patients with PsA were reportedly $5108 [8].

Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. The efficacy and safety of tofacitinib 5 and 10 mg twice daily have been demonstrated in two global phase 3 studies [9, 10] and a long-term extension study [11] in patients with PsA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or tumor necrosis factor inhibitor therapy. Tofacitinib adherence and persistence, both as monotherapy and in combination with csDMARDs, were recently evaluated over 6 months in a real-world setting in patients with PsA [12]. As a natural follow-up to that study, this current study further describes the analysis of adherence and persistence using a larger sample size and over a longer follow-up, and evaluates costs and HCRU in patients with PsA who were treated with tofacitinib as monotherapy and/or in combination with csDMARDs.

Methods

Data Sources and Study Design

Data from two health insurance databases, the Optum® Clinformatics® Data Mart (Optum CDM hereafter) and the Merative™ MarketScan® (MarketScan hereafter), were analyzed retrospectively in this study. Optum CDM is derived from a database of administrative health claims for members of a large national managed care company affiliated with Optum (United HealthCare). The database contains de-identified patient data from over 77 million patients in all 50 states in the USA, from both commercial and Medicare Advantage health plans, and includes medical and pharmacy claims, member eligibility, and inpatient confinements, plus standardized pricing for these data. MarketScan Research databases comprise data from the combined healthcare service used by a selection of large employers, health plans (preferred provider and health maintenance organizations, point of service, and indemnity), and government and public organizations. The database contains de-identified patient data from more than 273 million patients in the USA, and includes detailed costs, utilization, and outcomes for healthcare services performed in both the inpatient and outpatient settings.

Eligible patients had at least one tofacitinib prescription between December 4, 2017 and February 28, 2020, and were ≥ 18 years of age at the index date (first tofacitinib prescription). Patients were required to have ≥ 1 International Classification of Diseases code (10th revision) claim for PsA related to an inpatient diagnosis or ≥ 2 claims related to an outpatient diagnosis on different days and < 1 year apart at or during the 12 months pre-index; ≥ 12 months’ continuous medical and pharmacy enrollment pre-index; and ≥ 180 days continuous enrollment in a health plan post-index. Exclusion criteria included any prescription for tofacitinib at any time prior to index date within the available claims history; concurrent use of tofacitinib and a biologic DMARD at any point during the follow-up; and a diagnosis of rheumatoid arthritis at or during 12 months pre-index.

Study Cohorts

Data were analyzed in cohorts stratified by therapy type (monotherapy or combination therapy) and tofacitinib treatment episodes (on-treatment and off-treatment). Tofacitinib monotherapy was defined as the absence of csDMARD use (methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, thalidomide, penicillamine, tacrolimus, auranofin, aurothioglucose, azathioprine, chloroquine, cyclophosphamide, cyclosporine, gold sodium thiomalate, or minocycline) within 90 days on or after the index date. Tofacitinib combination therapy was defined as any csDMARD use within 90 days on or after the index date. Tofacitinib treatment episodes were defined as continuous use until there was a gap in treatment of > 60 days and were considered from the index date to the last claim for tofacitinib plus the number of days supplied. On-treatment was defined as the sum of time during a tofacitinib episode and off-treatment was defined as the sum of time outside of a tofacitinib episode.

Outcome Measures

Baseline demographics and characteristics of patients initiating tofacitinib in the monotherapy and combination therapy cohorts within each claims database were collected, including age, gender, insurance type, and PsA-related comorbidities.

Tofacitinib adherence and persistence were estimated for both the monotherapy and combination therapy cohorts from each claims database. Adherence was estimated both in terms of medication possession ratio (MPR) and proportion of days covered (PDC) at 6, 12, 18, and 24 months post-index. The MPR was calculated as total number of prescription days supply/(days from the first to the last prescription date + the last days supply). MPR was capped at 1.0 with a maximum number of 14 days of carryover allowed, and patients with only one prescription were not included. The PDC was calculated as (total number of prescription days − the number of stockpiled days)/respective fixed intervals [13, 14]. PDC was capped at 1.0 with a maximum number of 14 days of carryover allowed, and patients with only one prescription were included. Persistence (up to month 36) was estimated in terms of months of continuous medication use. Patients were considered non-persistent if a gap of ≥ 60 days was observed between the prescriptions.

Costs and HCRU were calculated during on-treatment and off-treatment episodes, including for the monotherapy and combination therapy cohorts in both claims databases. All-cause and PsA-related medical costs and HCRU were calculated for hospitalizations, emergency room visits, outpatient visits (emergency room visits, laboratory tests, and visits related to routine medical care), and outpatient pharmacy costs. Total medical costs were defined as the sum of costs in each of these settings. Costs were inflation-adjusted to 2020 US dollars. For MarketScan, only costs related to non-capitated plans were included, as claims that were flagged as being part of a capitated plan were not considered to contain accurate cost information. Optum CDM does not have this differentiation in the data.

Statistical Analysis

Descriptive statistics were presented as means and standard deviation (SD) or medians and interquartile ranges (IQRs) for continuous variables, and frequencies and proportions for categorical and dichotomous variables. Treatment persistence was analyzed by Kaplan–Meier survival analysis [15]. Missing or unavailable data were not included in the analysis. Costs were calculated on a per patient per month (PPPM) basis, which was modeled using a generalized linear model with a gamma distribution and log-link clustered on the patient [16, 17]. For HCRU outcomes, generalized estimating equations with a negative binomial distribution clustered on the patient were used to model PPPM utilization using a robust sandwich estimator [18,19,20]. All analyses were conducted using SAS/STAT software, Version 9.4 of the SAS System for Windows. Copyright© 2023 SAS Institute Inc, Cary, NC.

Ethics

The data were statistically de-identified, compliant with the Health Insurance Portability and Accountability Act of 1996, and the research was deemed exempt from institutional review board approval. Access to the Optum CDM and MarketScan databases was allowed under license for this study.

Results

Patient Demographics and Clinical Characteristics

In total, there were 9013 patients with PsA initiating tofacitinib in the study period from Optum CDM and 11,754 patients from MarketScan (see Table S1 in the electronic supplementary material). Following exclusion per the eligibility criteria, 274 patients from Optum CDM and 395 patients from MarketScan were included in this analysis. Patient baseline demographics and clinical characteristics can be found in Table 1.

Table 1 Patient baseline demographics and clinical characteristics
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In Optum CDM, the mean age was 54.4 years (standard deviation [SD] 12.4), the mean Charlson Comorbidity Index (CCI) score was 0.8 (SD 1.4), and the median follow-up period was 25.4 months (IQR 15.6). In MarketScan, the mean age was 51.4 years (SD 9.7), the mean CCI score was 0.5 (SD 1.0), and the median follow-up period was 15.6 months (IQR 11.0). The patient population was mainly female in both databases (Optum CDM, 70.4%; MarketScan, 68.9%). The insurance type was predominantly commercial in both databases (Optum CDM, 77.4%; MarketScan, 94.9%). The majority of patients were from the Southern region in both databases (Optum CDM, 54.0%; MarketScan, 45.8%). Approximately 96% of patients across both databases had at least one PsA-related comorbidity; the most common comorbidity was respiratory diseases followed by hypertension. In total, 175 (63.9%) patients in Optum CDM and 224 (56.7%) in MarketScan had concomitant psoriasis.

Within the first 90 days post-index, most patients in both database populations were receiving monotherapy vs combination therapy (Optum CDM, 74.1% vs 25.9%; MarketScan, 65.8% vs 34.2%). There were fewer female patients in the monotherapy vs combination therapy cohorts (67.0% vs 80.3%) in Optum CDM. Compared with the monotherapy cohorts, more patients in the combination therapy cohorts had Medicare insurance (monotherapy vs combination therapy: Optum CDM, 19.7% vs 31.0%; MarketScan, 4.6% vs 5.9%) and had a longer follow-up period (monotherapy vs combination therapy median [IQR] Optum CDM, 24.4 [16.6] vs 28.7 [14.8] months; MarketScan, 14.3 [10.6] vs 16.6 [12.2] months).

Fewer patients receiving monotherapy switched to combination therapy (addition of csDMARD) vs switching from combination therapy to monotherapy (removal of csDMARDs) at any time during the analysis in both database populations (see Table S2 in the electronic supplementary material).

Adherence and Persistence

In both database populations, the mean MPR was similar for both the monotherapy and combination therapy cohorts and was maintained over time (see Fig. S1a in the electronic supplementary material). At 6 months post-index, the proportion of patients with an MPR ≥ 0.8 was numerically lower in the monotherapy vs combination therapy cohorts in both database populations (Optum CDM, 70.0% vs 73.2%; MarketScan, 66.2% vs 75.6%) (Fig. 1a). This numerically lower pattern was maintained at 24 months post-index (Optum CDM, 62.2% vs 78.7%; MarketScan, 71.4% vs 73.1%). In comparison with the mean MPR, the mean PDC numerically decreased over time in both database populations for monotherapy and combination therapy (see Fig. S1b in the electronic supplementary material). At 6 months post-index, the proportion of patients with a PDC ≥ 0.8 was numerically lower in the monotherapy vs combination therapy cohort in both database populations (Optum CDM, 62.6% vs 67.6%; MarketScan, 58.1% vs 64.4%) (Fig. 1b). At 24 months post-index, this numerically lower pattern was maintained in the Optum CDM population but not in the MarketScan population (Optum CDM, 31.5% vs 44.7%; MarketScan, 31.4% vs 30.8%).

Fig. 1
figure 1

Adherence in patients with PsA initiating tofacitinib evaluated by a MPR ≥ 0.8 and b PDC ≥ 0.8. Optum CDM and MarketScan denote the Optum® Clinformatics® Data Mart and Merative™ MarketScan® databases, respectively. MPR and PDC were capped at 1.0 with a maximum number of 14 days of carryover allowed. N number of evaluable patients, n number of patients with adherence, MPR medication possession ratio, PDC proportion of days covered, PsA psoriatic arthritis

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The rates of tofacitinib persistence decreased over time in both the monotherapy and combination therapy cohorts across both databases (6 months post-index, range across both databases 53.1–70.4%; 30 months post-index, range across both databases 20.0–34.0%; Fig. 2a). The overall median time to tofacitinib discontinuation was 10.6 (95% confidence interval [CI] 8.3–13.1) months in the Optum CDM population and 7.7 (95% CI 6.1–9.9) months in the MarketScan population. Lower treatment persistence was observed for the monotherapy vs combination therapy cohorts in both databases (Fig. 2b, c); however, statistical significance (at the 0.05 level of significance) was not found (median [95% CI] Optum CDM, 10.1 [7.4–11.8] vs 16.7 [8.3–26.6] months, log-rank P = 0.0663; MarketScan, 6.9 [5.6–9.4] vs 11.0 [6.1–13.9] months, log-rank P = 0.1152).

Fig. 2
figure 2

a Persistencea in the Optum CDM and MarketScan populations, and time to treatment discontinuation in patients with PsA initiating tofacitinib in the b Optum CDM and c MarketScan populations. Optum CDM and MarketScan denote the Optum® Clinformatics® Data Mart and Merative™ MarketScan® databases, respectively. Shading represents 95% Hall-Wellner confidence bands. aPersistence was estimated in terms of months of continuous medication use. Patients were considered non-persistent if a gap of ≥ 60 days was observed between the prescriptions. N number of evaluable patients, PsA psoriatic arthritis

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Costs and HCRU

Within the study period, the all-cause total medical costs for the overall patient populations were $5829 PPPM in Optum CDM and $4805 PPPM in MarketScan (Fig. 3a) and PsA-related total medical costs were $3954 PPPM and $3445 PPPM, respectively (Fig. 3b).

Fig. 3
figure 3

Total medical costs in patients with PsA initiating tofacitinib for a all-cause events stratified by treatment episode, b PsA-related events stratified by treatment episode, c all-cause events stratified by treatment type and episode, and d PsA-related events stratified by treatment type and episode. Optum CDM and MarketScan denote the Optum® Clinformatics® Data Mart and Merative™ MarketScan® databases, respectively. Total cost calculated as the sum of hospital admission, outpatient, and emergency room visit costs, and outpatient pharmacy cost. All costs are presented as PPPM and are inflation-adjusted to 2020 USD. Error bars indicate 95% CI. CI confidence interval, PsA psoriatic arthritis, PPPM per patient per month, USD US dollars

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The overall all-cause total medical costs were numerically similar for patients receiving monotherapy and combination therapy in Optum CDM database ($5819 and $5855 PPPM, respectively), but numerically lower for the monotherapy vs combination therapy cohorts ($4539 vs $5270 PPPM) in MarketScan (Fig. 3c).

In comparison, overall PsA-related total medical costs were numerically lower for the monotherapy vs combination therapy cohorts in both Optum CDM ($3869 vs $4173 PPPM) and MarketScan ($3245 vs $3795 PPPM) (Fig. 3d). During off-treatment vs on-treatment periods, numerical cost decreases were observed for all-cause costs (Optum CDM, $5383 vs $6149; MarketScan, $4145 vs $5180) and PsA-related costs (Optum CDM, $3237 vs $4515; MarketScan, $2703 vs $3907), including in patients receiving monotherapy or combination therapy, which was primarily driven by numerical decreases in pharmacy costs off-treatment (see Table S3 in the electronic supplementary material).

All-cause and PsA-related HCRU stratified by treatment episode can be found in Table 2 and stratified by treatment episode and therapy type in Table 3. The number of outpatient visits generally increased numerically during off-treatment vs on-treatment periods for all-cause (Optum CDM, 2.37 vs 2.05 visits PPPM; MarketScan, 2.15 vs 1.99 visits PPPM) and PsA-related (Optum CDM, 0.60 vs 0.46 visits PPPM; MarketScan, 0.47 vs 0.44 visits PPPM) events. Outpatient costs were also numerically increased during off-treatment vs on-treatment periods and can be found in Table S3 in the electronic supplementary material.

Table 2 All-cause and PsA-related HCRU in patients with PsA initiating tofacitinib stratified by treatment episodes
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Table 3 All-cause and PsA-related HCRU in patients with PsA initiating tofacitinib stratified by therapy type and tofacitinib episodes
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In general, all-cause and PsA-related outpatient visits were numerically lower in the monotherapy vs combination therapy cohorts and increased numerically for both therapy types in off-treatment vs on-treatment periods, with exceptions to these observations in the MarketScan PsA-related data (Table 3). The overall number of all-cause medications prescribed was numerically higher during off-treatment vs on-treatment periods in the Optum CDM population (4.56 vs 4.33 prescriptions PPPM), whereas a numerically lower number was observed during off-treatment vs on-treatment periods in the MarketScan population (3.73 vs 4.19 prescriptions PPPM) (Table 2). This increase in medications prescribed in the Optum CDM population was driven by numerical increases in off-treatment vs on-treatment opioid (0.32 vs 0.19 prescriptions PPPM), biologic (0.32 vs no prescriptions PPPM), and non-PsA-related medications (3.36 vs 2.80 prescriptions PPPM) (Table 2).

In comparison, the overall number of PsA-related medications prescribed was numerically lower during off-treatment vs on-treatment periods in both the Optum CDM (1.21 vs 1.53 prescriptions PPPM) and MarketScan populations (1.05 vs 1.48 prescriptions PPPM) (Table 2). The numbers of all-cause and PsA-related emergency room visits were relatively low regardless of therapy type and treatment episode (≤ 0.1 visits PPPM) (Table 3).

Discussion

Unlike other advanced treatments approved for use in PsA [23,24,25], there is currently a lack of knowledge on the long-term, real-world treatment patterns and economic burden of tofacitinib-treated patients with PsA.

In a recent study of US claims data from MarketScan, patients with PsA initiating tofacitinib as monotherapy had numerically lower adherence at 6 months vs patients receiving combination therapy (PDC ≥ 0.8, 56.8% vs 65.5%; MPR ≥ 0.8, 82.7% vs 88.3%) [12]. The current retrospective study extends these results through the inclusion of a larger sample size across two claims databases, a longer follow-up, and cost and utilization outcomes.

In this study, most patients were receiving monotherapy vs combination therapy and more patients switched from combination therapy to monotherapy vs switching from monotherapy to combination therapy. Similar to the observations made previously [12], tofacitinib adherence was generally numerically lower in patients receiving monotherapy vs combination therapy. However, these comparisons were only descriptive in nature. High levels of adherence were observed in the current study up to 24 months when measured as MPR ≥ 0.8; however, adherence measured as PDC ≥ 0.8 numerically declined over time (range across both databases at 6 months, 58.1–67.6%; 12 months, 36.4–49.2%; 24 months, 30.8–44.7%). As PDC adjusts for overlapping days of coverage (e.g., early prescription refills), it provides a more conservative estimate of adherence compared with MPR [26]. These rates of adherence were generally similar to that observed in a real-world administrative claims study of patients with PsA receiving various biologics and targeted synthetic (ts)DMARDs for 12 months by Murage and colleagues: adherence (PDC ≥ 0.8) to the index drug varied from 21.0% for ustekinumab to 48.2% for intravenously administered golimumab, with 46.0% of patients being adherent to tofacitinib [27]. Comparisons of this study to that by Murage and colleagues suggest that tofacitinib adherence in a real-world setting is consistent with other advanced PsA therapies.

The results of this study suggest decreased tofacitinib persistence for those patients receiving monotherapy vs combination therapy; however, no statistical differences were observed. Persistence rates varied across both databases from 53.1–70.4% at 6 months to 35.6–55.8% at 12 months, decreasing over time. These persistence rates were generally similar to real-world tofacitinib persistence rates (< 60-day gap) reported in two different studies: 69.8–73.1% at 6 months and 54.1% at 12 months [12, 27]. Murage and colleagues reported that persistence rates at 12 months for other selected biologics and tsDMARDs ranged from 31.5% for ustekinumab and 59.3% for subcutaneously administered golimumab [27], suggesting that the rates of persistence observed in this study are consistent with other advanced PsA therapies. The median time to treatment discontinuation (≥ 60-day gap) in the current study was 10.6 or 7.7 months depending on the database used. In comparison, the mean time to tofacitinib discontinuation with a ≥ 90-day gap reported by Murage and colleagues was 123.0 days (SD 82) [27], which may be reflective of the longer gap used vs this study.

The overall PsA medical costs in this study (Optum CDM, $3954 PPPM; MarketScan, $3445 PPPM) were similar to those reported for tofacitinib by Murage and colleagues ($3486 PPPM) [27]. The overall all-cause and PsA-related costs and number of outpatient visits were generally numerically lower in patients receiving tofacitinib monotherapy vs combination therapy. Nevertheless, the decreases between combination therapy and monotherapy were not large, and a similar study in patients with rheumatoid arthritis found no significant difference in costs between patients receiving tofacitinib as monotherapy vs combination therapy [28]. During off-treatment vs on-treatment periods in this study, costs and PsA-related medications numerically decreased, and outpatient visits numerically increased. The use of opioids, which have been reported to have a notably high use in patients with PsA [29], numerically increased when patients were off-treatment vs on-treatment in this study, which may contribute to future negative consequences for these patients [30].

Limitations of this study include those that are inherent to the retrospective design, such as potential errors or omissions in claims data. The medications taken by the patients for which they have filed a claim may not be assured because of the potential miscoding of the diagnosis of PsA, rheumatoid arthritis, and other autoimmune conditions. In addition, the diagnosis of PsA may not have been clinically validated and there is a possibility of bias regarding diagnosis; however, given this study concerned patients that received tofacitinib there is some degree of confidence that these patients were diagnosed for a tofacitinib-approved condition. Further, patients with rheumatoid arthritis were excluded from this study and there were no patients with Crohn’s disease included, suggesting the bias of misdiagnosis would be low. There was no information available regarding severity of the disease, which can impact the outcomes assessed in this study. It is presumed that patients with more severe illness will use more resources and perhaps take more concomitant treatment (i.e., steroids or opioids). In addition, less severe cases may lead to lower adherence rates compared with more severe cases. While both databases utilized in this study are large, Optum CDM consists of patients with United HealthCare insurance coverage and MarketScan consists of patients from large employers, which may affect generalizability to the general PsA population. In addition, it is likely that a larger sample size than that included in this study is required to detect statistical significance and confirm the trends found in this study. The reasons for lack of persistence or switching from monotherapy to combination therapy were not obtained and, as such, decisive conclusions could not be reached. Finally, an active comparator was not included in this study, which could be included in future studies.

Conclusion

These results demonstrate that tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased during off-treatment vs on-treatment periods, irrespective of whether patients had received monotherapy or combination therapy, which was driven by numerically lower medication costs. This study provided further understanding of tofacitinib use in patients with PsA in a real-world setting; however, studies investigating patient characteristics could help to determine the main factors associated with tofacitinib economic burden and compliance.