FormalPara Key Points

The characteristics of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry participants with rheumatologist-diagnosed psoriatic arthritis initiating the interleukin-23 p19-subunit inhibitor, guselkumab, are described.

Registry participants with psoriatic arthritis initiating guselkumab had active peripheral joint and skin disease, with substantial pain and fatigue.

Most (76%) registry participants with psoriatic arthritis initiating guselkumab had previously received two or more biologic disease-modifying antirheumatic drugs.

1 Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease associated with active psoriasis or a prior history of psoriasis [1]. It is sometimes also associated with related conditions such as inflammatory bowel disease (IBD) and uveitis [2, 3]. The clinical manifestations of PsA can include peripheral arthritis, axial disease, skin and nail disease, dactylitis, and enthesitis [2,3,4,5]. The presence and severity of clinical manifestations vary widely by patient, from mild joint inflammation to severe debilitating joint damage with skin and nail involvement [6]. Treatment recommendations reflect the severity and heterogeneity of PsA disease activity, as well as the domains affected in a particular patient [2,3,4, 6,7,8,9].

Consensus guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the American College of Rheumatology/National Psoriasis Foundation, and the European Alliance of Associations for Rheumatology advocate selecting the most appropriate therapy to broadly address the PsA disease domains present in individual patients [2, 7, 10]. Current treatment recommendations include nonpharmacologic therapies, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), and biologic DMARDs (bDMARDs) [2, 7, 9, 10]. In the most recent update of the GRAPPA treatment recommendations, the use of selective interleukin-23 inhibitors to treat a variety of PsA manifestations, including peripheral arthritis (regardless of prior use of DMARDs), enthesitis, dactylitis, and skin and nail symptoms, was strongly supported [10].

Guselkumab is a high-affinity human monoclonal antibody that selectively inhibits the p19 subunit of interleukin-23. The efficacy and safety of guselkumab in patients with active PsA were evaluated in two phase III trials (DISCOVER-1 and DISCOVER-2) [11,12,13,14,15] and a phase IIIb trial (COSMOS) [16]. In DISCOVER-1 (biologic-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients), DISCOVER-2 (biologic-naïve patients), and COSMOS (patients with inadequate TNFi response), guselkumab was superior to placebo in relieving signs and symptoms of joint and skin manifestations of PsA and improving health-related quality of life and physical function at week 24 [11, 12, 16]. Response rates and average improvements in guselkumab-treated patients were sustained or numerically increased through 1 [13, 14] and 2 years [15]. In addition, in a recent Bayesian network meta-analysis, a primary endpoint assessment of guselkumab at week 24 demonstrated favorable arthritis efficacy comparable to that of drugs with other mechanisms of action, such as interleukin-17A inhibitors and subcutaneous TNFis, while offering a better Psoriatic Area and Severity Index response relative to many other treatments [17].

Guselkumab has been approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis and those with active PsA, the latter approved in July 2020 [18]. Thus, limited information is available about the use of guselkumab in patients with PsA outside of clinical trials. The CorEvitas Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) prospective observational registry includes detailed information about patients with rheumatologist-diagnosed PsA. The objective of this study was to describe the characteristics of patients enrolled in the CorEvitas PsA/SpA Registry who initiated therapy with guselkumab for the treatment of PsA. To our knowledge, this is one of the first reports to describe such a patient population.

2 Patients and Methods

2.1 Data Source

The CorEvitas PsA/SpA Registry was launched in March 2013 and is a US-based, prospective, multicenter, noninterventional registry of patients with PsA or SpA who are under the care of a rheumatologist. As of 30 September, 2021, patients were recruited from 65 private and academic sites across 30 states, through 70 participating healthcare providers. During routine clinical visits occurring approximately every 6 months, patients and providers complete questionnaires capturing information on patient demographics, disease characteristics, PsA medication history, medical history and lifestyle characteristics, disease activity and severity, comorbidities, and adverse events (including infections, hospitalizations, and other targeted safety outcomes). Although other diagnostic tests and blood collection are not required for participation, relevant laboratory and imaging results are reported when available. As of 30 September, 2021, the registry included approximately 5260 patients.

Inclusion and exclusion criteria for the CorEvitas PsA/SpA Registry are described in Table S1 of the Electronic Supplementary Material (ESM). Briefly, the registry includes adults aged 18 years or older who have provided written consent and who have been diagnosed with PsA, the majority of whom fulfill Classification Criteria for Psoriatic Arthritis [19]. If axial PsA is present, they may also then meet the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial SpA [20] or the modified New York classification criteria for ankylosing spondylitis (AS) [21]. Registry participants must also be prescribed or starting an eligible medication for the treatment of PsA, axial SpA, or AS. Patients are excluded if they have been diagnosed with any other form of autoimmune inflammatory arthritis (such as rheumatoid arthritis or systemic lupus erythematosus) and/or were participating in or planning to participate in clinical trials in which a nonmarketed or marketed investigational drug is provided.

2.2 Analysis Population

This analysis included patients with rheumatologist-diagnosed PsA who enrolled in the registry between 1 March, 2013, and 30 September, 2021, and initiated guselkumab at or after registry enrollment. Both biologic-naïve and biologic-experienced patients were included in this analysis if they had not received guselkumab therapy prior to enrollment and could be assigned an initiation visit. An initiation visit was defined as the visit where guselkumab was first administered or prescribed for initiation.

2.3 Assessments

At registry enrollment, the rheumatologist completes questionnaires ascertaining information on patient medical history, including all prior and current treatment start and stop dates for PsA/SpA medications, and inclusive of all history prior to registry enrollment based on patient medical records. At each routine follow-up CorEvitas visit that occurs approximately every 6 months for patients enrolled in the registry (180 days from the last registry visit with a minus 30-day window or ≥ 150 days from the last eligible registry visit), information on therapy changes since the last visit is recorded. Data collected also include patient demographics (age, sex, and race), lifestyle characteristics (smoking status, alcohol use, and body mass index), comorbidities, PsA clinical features, calculated PsA disease activity measures, and patient-reported outcome measures. This analysis included patient-reported and provider-reported data collected during the guselkumab initiation visit, including reasons for guselkumab initiation, or previous routine visits.

Rheumatologists document the patients’ histories of comorbidities, including uveitis, IBD (Crohn’s disease, ulcerative colitis, possible IBD, and/or other IBD), cerebro-cardiovascular disease (see ESM), hypertension, diabetes mellitus, osteoporosis, fibromyalgia, depression, and anxiety. Providers also document PsA clinical features information, including time since onset of PsA symptoms, time since PsA diagnosis, body surface area (BSA) affected by psoriasis, tender joint count (0–68), swollen joint count (0–66), Physician Global Assessment of PsA score (visual analog scale (VAS) 0–100) [22], Physician Global Assessment of PsA and Psoriasis score (VAS 0–100) [23], nail psoriasis VAS score (0–100), dactylitis count (0–20) [24], the Spondyloarthritis Research Consortium of Canada Enthesitis Index score (0–16) [25], and the Leeds Enthesitis Index (0–6) score [24]. Axial involvement was determined based on the following physician-reported criteria: diagnosis of axial SpA (nonradiographic or radiographic) or AS, physician-indicated spinal involvement or completed any of the mobility measurements [includes occiput-to-wall distance, lateral lumbar flexion, and lumbar flexion (Schöber)], or selected any of the clinical features criteria for diagnosing axial SpA [26] (see details in Table S2 of the ESM).

Disease activity was measured using standard calculated efficacy assessment tools such as the Clinical Disease Activity Index [27], Disease Activity Index for PsA (DAPSA) [28,29,30], clinical DAPSA [29], achievement of Minimal Disease Activity (MDA) [30,31,32] or Very Low Disease Activity (VLDA) [30,31,32] (defined as meeting at least five or all seven, respectively, of the following criteria: tender joint count ≤ 1, swollen joint count ≤ 1, Psoriatic Area and Severity Index ≤ 1 or BSA ≤ 3, patient pain VAS ≤ 15, Patient Global Disease Activity VAS ≤ 20, health assessment questionnaire ≤ 0.5, and tender entheseal points ≤ 1), PsA Disease Activity Score (PASDAS) [32], and ASDAS employing C-reactive protein (ASDAS-CRP; in a subgroup of patients with axial involvement) [33, 34]. Table S2 of the ESM provides additional details about these measures.

Patient-reported outcome measures that were assessed were modified Routine Assessment of Patient Index Data 3 [35, 36], patient-reported pain (VAS 0–100), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, 0–10; in a subgroup of patients with axial involvement) [37], Patient Global Assessment of Arthritis (VAS 0–100) [38], Patient Global Assessment of Arthritis and Psoriasis (VAS 0–100) [38], Bath Ankylosing Spondylitis Functional Index (0–10; in a subgroup of patients with axial involvement) [39], the Health Assessment Questionnaire Disability Index [40], the Health Assessment Questionnaire for Spondyloarthropathies [40], and the ASAS Health Index (in a subgroup of patients with axial involvement) [41]. Table S2 of the ESM provides additional details about these measures.

2.4 Statistical Analyses

For those patients who initiated guselkumab during a CorEvitas PsA/SpA Registry visit, data were utilized from that visit. For patients whose guselkumab initiation occurred between registry visits, data from the prior visit were used if that visit was within 4 months prior to initiation. If the prior visit occurred more than 4 months before guselkumab was started, data were utilized from the first subsequent registry visit after guselkumab initiation if this visit was within 3 months after the start of therapy. If the subsequent visit was more than 3 months after guselkumab initiation, patients were excluded from this analysis. Data collected were summarized using descriptive statistics: counts and percentages for categorical variables and means and standard deviations (SDs) and/or medians and interquartile ranges for continuous variables. All analyses were performed using Stata 16 (College Station, TX, USA).

3 Results

Of the 5260 patients enrolled in the CorEvitas PsA/SpA Registry as of 30 September, 2021, 4250 were diagnosed with PsA (Fig. 1). One hundred and thirteen of these registry participants initiated guselkumab at or after registry enrollment and were included in this analysis (Fig. 1). The first instance of guselkumab initiation identified was on 1 June, 2018. Mean (SD) age of these patients was 53.2 (12.5) years, 63% were female, and 90% were White (Table 1). Mean (SD) body mass index was 33.7 (8.8) kg/m2, reflecting a predominantly obese (67%) population. The most prevalent comorbidities were hypertension (32%), depression (30%), diabetes (26%), anxiety (13%), and cerebro-cardiovascular disease (11%). Of note, 7.1% of patients had IBD (ulcerative colitis, Crohn’s disease, possible IBD, and/or other IBD) and 3.5% had uveitis. In 3 of 113 (2.7%) patients, guselkumab initiation occurred between registry visits. Data for these patients were taken from the first registry visit after guselkumab initiation if it occurred within 3 months of the start of therapy.

Fig. 1
figure 1

Flowchart of the selection of analysis population. Selection criteria were applied to the registry population from inception of the registry, 1 March, 2013, through 30 September, 2021. The first instance of guselkumab initiation identified was on 1 June, 2018, and data reported through 30 September, 2021, were used for the analysis. b biologic, DMARDs disease-modifying antirheumatic drugs, PsA psoriatic arthritis, SpA spondyloarthritis, ts targeted synthetic

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Table 1 Demographics, lifestyle characteristics, and related conditions among patients in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry with psoriatic arthritis who initiated guselkumab
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Registry participants who initiated guselkumab had been diagnosed with PsA for a mean (SD) of 9.5 (9.4) years and had a mean (SD) duration of 13.9 (11.3) years since PsA symptom onset prior to guselkumab initiation (Table 2). Eighty-nine percent of patients had a current or personal history of psoriasis. Among all patients with evaluable data, median (interquartile range) BSA affected by psoriasis was 4% (9%), although 27% had ≥ 10% BSA affected by psoriasis, and most had moderate nail psoriasis, with a mean (SD) nail psoriasis VAS score of 7.6 (14.5). Mean (SD) tender and swollen joint counts were 6.8 (8.8) and 2.0 (3.5), respectively, and mean (SD) dactylitis counts were 0.2 (0.7) among the total population and 1.9 (1.2) among the 12 (11%) patients with a dactylitis count ≥ 1. Twenty (22%) patients had a Leeds Enthesitis Index score ≥ 1, and 32 (28%) had a Spondyloarthritis Research Consortium of Canada Enthesitis Index score ≥ 1; the mean (SD) scores among these patients were 1.8 (1.0) and 3.1 (2.1), respectively. Axial involvement was identified in 49% of patients. Additionally, mean (SD) Physician Global Assessment of PsA score was 33.3 (23.4), and mean (SD) Physician Global Assessment of PsA and psoriasis score was 39.5 (23.7).

Table 2 Clinical characteristics and previous and current medication use among patients in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry with psoriatic arthritis who initiated guselkumab
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Among patients who had initiated guselkumab, 71% had ever previously received a csDMARD, 91% had ever previously received a bDMARD (76% had previously received two or more bDMARDs), 81% had ever previously received a TNFi bDMARD (48% had previously received two or more TNFis), and 46% had ever previously received a tsDMARD (note that these categories are not mutually exclusive) (Table 2). Seven patients (6%) were b/tsDMARD naïve. Approximately 81% of patients in this analysis received guselkumab as a monotherapy, 15% received concomitant methotrexate, and 4.4% received a csDMARD other than methotrexate. The last b/tsDMARD therapy for PsA prior to guselkumab initiation was a TNFi in 32% of patients, a non-TNFi bDMARD in 49% of patients, and a tsDMARD in 19% of patients, with a median (interquartile range) duration of use of 7.0 (13) months. Approximately half (51%) of all participants discontinued their last therapy for PsA because of lack of efficacy, whereas others cited safety (9.7%), insurance (1.8%), or other (6%) reasons for discontinuation, including patient preference, tolerability, frequency or route of administration, and cost; data were missing in 34% of participants. The reasons cited for initiation of guselkumab included active disease (84%), safety (1%), insurance (1%), and other (14%) reasons; data were missing in 5% of participants.

The mean (SD) clinical DAPSA score of the overall population was 19.1 (13.1), indicative of a population with moderate disease activity, while 82% of patients did not demonstrate MDA or VLDA (Table 3). Among the 12 of 13 patients who had MDA and provided a reason for guselkumab initiation, the reason for initiating guselkumab was active disease (i.e., inadequate initial response, failure to maintain initial response, or active disease (initially or a flare) leading to initiating a medication or changing the dose/frequency) in 11 patients and other (i.e., fear of future side effect, temporary interruption, patient preference, to improve compliance, to improve tolerability, frequency of administration, route of administration, alternate mechanism of action, and patient doing well) in one patient. Active disease was the reason for guselkumab initiation provided by all three patients in VLDA who initiated guselkumab. Mean [SD] scores for other calculated disease activity measures, including the Clinical Disease Activity Index (13.6 [9.0]), DAPSA (21.1 [14.8]), PASDAS (4.4 [1.6]), and ASDAS-CRP (3.3 [1.4], in patients with axial involvement) also consistently demonstrated that patients were experiencing moderate levels of disease activity at the time of guselkumab initiation. It should be noted that the sample number for ASDAS-CRP (n = 11) is small and should be interpreted with caution.

Table 3 Disease activity measures among patients in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry with psoriatic arthritis who initiated guselkumab
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The mean (SD) BASDAI score of 5.8 (2.0) in patients with axial involvement was also indicative of a population with active disease using cut-off points originally developed for axial SpA (Table 4). These results were consistent with the moderately high mean (SD) patient-reported pain, fatigue, and spine pain (spine pain reported only in patients with axial involvement) VAS scores of 54.0 (26.0), 51.8 (26.9), and 56.6 (25.7), respectively; the mean (SD) patient global assessment of arthritis VAS score of 48.5 (24.8); and the mean (SD) patient global assessment of arthritis and psoriasis VAS score of 49.9 (24.7). In addition, mean [SD] Health Assessment Questionnaire Disability Index and Health Assessment Questionnaire for Spondyloarthropathies scores (both 0.9 [0.7]) and Bath Ankylosing Spondylitis Functional Index (5.2 [2.4]) and ASAS Health Index (7.9 [4.8]) values, the latter two in the subgroup of patients with axial involvement, indicated moderately to severely impaired functioning at guselkumab initiation. The mean (SD) modified Routine Assessment of Patient Index Data 3 (4.1 [2.0]) was below the cut-off point for moderate disease (6.1–12.0).

Table 4 Patient-reported outcomes among patients in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry with psoriatic arthritis who initiated guselkumab
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4 Discussion

This observational analysis is one of the first reports describing the clinical characteristics of registry participants initiating guselkumab for PsA. At the time these patients started guselkumab therapy for PsA, they were experiencing active PsA across multiple domains, as demonstrated by mean tender and swollen joint counts; DAPSA, PASDAS, and BASDAI scores; the low proportion of patients (14%) in MDA; and the moderate levels of functional impairment. In addition, 49% of patients in this population had axial involvement, which is within the 25–70% range reported for patients with PsA [42]. This proportion is higher than the 12.5% previously reported for the CorEvitas PsA/SpA Registry, although that historical analysis used different criteria to define axial involvement than what were used for the current analysis [43]. The substantial proportion of patients with axial involvement may be indicative of a treatment-resistant population who are early adopters of a new PsA therapy. Indeed, the patients in this analysis generally reported inadequate disease control despite having received multiple prior therapies for PsA, thus highlighting the need for PsA treatments with new mechanisms of action.

Although the efficacy of guselkumab in patients with PsA axial disease has not been evaluated in a dedicated randomized controlled trial to date, axial symptoms were evaluated in 312 patients in the pivotal, randomized, placebo-controlled, phase III trials of guselkumab in PsA (DISCOVER-1 and DISCOVER-2) who had investigator- and imaging-confirmed sacroiliitis [44]. A post hoc analysis of pooled data from this subgroup of patients (guselkumab every 4 weeks [N = 103], guselkumab every 8 weeks [N = 91], and placebo [N = 118]) demonstrated that guselkumab resulted in greater mean improvements in BASDAI (including the individual component on spinal pain) and ASDAS compared with placebo at week 24, with improvements sustained through 1 year. A dedicated, prospective randomized controlled trial of guselkumab in patients with PsA axial disease is currently ongoing (NCT04929210) [47].

In this registry setting, most patients were biologic experienced; 91% of patients had previously received a bDMARD and 48% had previously received two or more TNFis. In contrast, per eligibility requirements, only 31% of patients in DISCOVER-1 and no patients in DISCOVER-2 were biologic experienced [11, 12]. In the randomized, double-blind, placebo-controlled, phase IIIb COSMOS trial, which assessed guselkumab in patients with PsA with inadequate response to TNFis, patients had prior treatment with either one (88%) or two (12%) TNFis [16]. Notably, in the current study, most patients (81%) initiated guselkumab as monotherapy, although 19% of patients were receiving a concomitant csDMARD, the majority of which was methotrexate (15%). Use of guselkumab as monotherapy in patients with PsA is supported by prespecified subgroup analyses from the DISCOVER-1, DISCOVER-2, and COSMOS trials, which showed a consistent clinical response whether patients received guselkumab plus methotrexate or guselkumab alone [11, 12, 16].

Although the patients in this analysis had active disease despite being primarily biologic experienced, they had less severe disease, on average, compared with the patients in the DISCOVER trials, likely because of the minimum swollen and tender joint counts and CRP levels required for eligibility for these trials [11, 12]. Across treatment groups, DISCOVER-1 and DISCOVER-2 participants had higher mean baseline tender and swollen joint counts and DAPSA, PASDAS, and BASDAI scores than the patients in the analysis presented here [44, 45]. However, impairment of physical function and patient-reported pain scores were similar between the patient populations. Disease activity in the COSMOS trial population was similar to that in the DISCOVER trials [16]. It should also be noted that, in three patients, disease activity data were derived from the first subsequent registry visit after guselkumab initiation within 3 months of the start of therapy, which could have affected these results.

The demographic and disease characteristics at initiation of guselkumab in the registry participants presented here are similar to those from a recent observational study of a cohort of 24 patients from two Italian joint dermatology-rheumatology clinics with recently diagnosed PsA (≤ 2 years’ duration) who initiated guselkumab [46]. However, a smaller proportion of patients in the Italian study had prior treatment with bDMARDs. The registry participants who initiated guselkumab in this analysis and in the Italian study still had active disease despite many having previously used bDMARDs, with the majority of patients (76%) in this analysis having previously used two or more bDMARDs, suggesting harder to control disease that has not responded to previous therapies for PsA. This is consistent with the fact that 84% of the patients in this analysis initiated guselkumab because of active disease, and 51% cited a lack of efficacy as the reason for discontinuing their last therapy for PsA prior to guselkumab.

This analysis was limited to patients initiating guselkumab for PsA; thus, no comparisons can be made and findings cannot be generalized to patients starting other biologics. Other limitations of this analysis are the small number of patients included, with even fewer patients with evaluable data for some assessments such as ASDAS-CRP, although this is expected given the recent approval of guselkumab to treat patients with active PsA. It is also possible that drug benefit design and formulary status changes could have limited the number of patients who initiated guselkumab. Additionally, because this sample of patients with PsA is restricted to those who have regular visits with their healthcare provider, these results may not be representative of all US adults with PsA initiating guselkumab. Because of the limited number of biologic-naïve (n = 10) versus biologic-experienced (n = 103) patients, subgroup analyses were not performed. Additionally, if subgroups of patients (i.e., sicker or healthier patients) were routinely enrolled or not enrolled in the registry, selection bias could be introduced, thereby limiting the ability to generalize the results. Furthermore, the registry is not an inception cohort and relies on patient self-reporting or having been with the same clinician for an extended period. Patients may not recall their complete medication history, leading to an incomplete or inaccurate description of prior medication use. Registry participants could also have had undiagnosed or unreported confounding conditions or comorbidities with symptoms that overlap, such as central sensitization. Lastly, potential differences in patient profiles may exist among patients treated with guselkumab off-label prior to US Food and Drug Administration approval for active PsA, although the number of patients in this subset is small (n = 13).

5 Conclusions

Active peripheral joint and skin disease, elevated levels of self-reported pain, impaired physical function, substantial fatigue, and a relatively high proportion of patients with axial disease were observed at guselkumab initiation in this analysis of participants with PsA from the CorEvitas PsA/SpA Registry. We report an extensive amount of data allowing for a detailed characterization of patients with PsA who initiated guselkumab in routine clinical practice, thereby complementing the data pertaining to the homogenous patient population meeting the rigorous inclusion and exclusion criteria of phase III clinical trials. As additional patients initiating guselkumab for PsA continue to enroll in the CorEvitas PsA/SpA Registry, further analyses to investigate the clinical characteristics of patients initiating guselkumab and effectiveness of this therapy over time in this patient population will be conducted.