FormalPara Key Summary Points

Why carry out this study?

Guselkumab, a fully human, selective, interleukin-23p19-subunit inhibitor, demonstrated significant efficacy in reducing the signs and symptoms of psoriatic arthritis (PsA) in phase 3 studies and was approved by the Food and Drug Administration July 13, 2020 for adults with active PsA.

Real-world data on the effectiveness of guselkumab in adults with active PsA are currently limited.

We evaluated the effectiveness of guselkumab in a real-world setting utilizing data from a cohort of adults with active PsA from the CorEvitas PsA/Spondyloarthritis Registry, who had persistent on-label guselkumab use at their 6-month follow-up visit.

What was learned from the study?

In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, nearly 80% of patients who initiated treatment with on-label guselkumab had persistent use at the 6-month follow-up visit.

Significant improvements in PsA peripheral joint and skin disease and patient-reported pain were observed in patients with 6 months of persistent on-label guselkumab use.

The findings from this analysis offer valuable insights on the effectiveness of guselkumab in treating adults with active PsA seen in routine clinical practice in the United States.

Digital Features

This article is published with digital features, including a graphical abstract, to facilitate understanding of the article. To view digital features for this article go to: https://doi.org/10.6084/m9.figshare.23748942.

Introduction

Approximately 30% of the more than 7.5 million adults in the United States (US) with psoriasis develop psoriatic arthritis (PsA), [1] a chronic inflammatory disease that is characterized by involvement across distinct domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis [2,3,4]. Uncontrolled active PsA has been associated with profound functional disability, diminished quality of life, and accelerated mortality [2,3,4].

The heterogeneous nature of PsA necessitates treatment individualized by symptom severity, clinical manifestations, and comorbidities [3,4,5,6]. Treatment recommendations include nonpharmacologic therapies and conventional synthetic (cs), targeted synthetic (ts), or biologic (b) disease-modifying antirheumatic drugs (DMARDs) [4, 5, 7]. In the 2021 update of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis treatment recommendations, the use of biologics, including selective interleukin-23 inhibitors, was strongly recommended to treat various PsA manifestations, such as peripheral arthritis (regardless of prior csDMARD use), enthesitis, dactylitis, and skin and nail psoriasis [4].

Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the US Food and Drug Administration (FDA) to treat moderate-to-severe plaque psoriasis in July 2017 and to treat active PsA on July 13, 2020 [8, 9]. In the pivotal, phase 3, placebo-controlled DISCOVER-1 [10] and DISCOVER-2 [11] PsA trials, guselkumab demonstrated significant efficacy across joint, skin, and health-related quality of life outcomes and exhibited a positive benefit–risk profile among both biologic-naïve and tumor necrosis factor inhibitor (TNFi)-experienced individuals with active PsA. Findings from the subsequent Phase 3b COSMOS trial further demonstrated guselkumab efficacy and safety in patients with active PsA and inadequate response to TNFi (TNFi-IR) [12].

Given the relatively recent approval of guselkumab for treating active PsA, real-world data on its effectiveness in this population are limited. We previously described the characteristics of a cohort of patients with rheumatologist-diagnosed, active PsA in the US-based CorEvitas PsA/Spondyloarthritis (SpA) Registry who initiated guselkumab [13]. At guselkumab initiation, these registry participants had active peripheral joint and skin disease and reported substantial pain; a considerable proportion also had axial involvement. The current study evaluated guselkumab real-world effectiveness utilizing data from patients with PsA in the CorEvitas PsA/SpA Registry who initiated guselkumab treatment and had an eligible 6-month follow-up visit. Herein, we report changes in key clinical disease activity outcomes among registry participants who initiated on-label guselkumab treatment and had persistent use through the 6-month follow-up visit.

Methods

Data Source

The CorEvitas PsA/SpA Registry, initiated in 2013, is a US, prospective, multicenter, observational registry of patients with PsA or SpA under the care of rheumatologists. Registry enrollment criteria were previously reported [13] and are detailed in Supplementary Material Table 1. The registry collects data from rheumatologists practicing in private or academic settings and from patients during their clinical visits. At enrollment, a patient’s medical history, including prior and current PsA treatment, is captured from medical records. Longitudinal data are collected from patients and their treating rheumatologist during routine follow-up visits occurring approximately every 6 months (180 days from the last registry visit within a window of − 30 to + 90 days).

Table 1 Demographics, lifestyle characteristics, comorbidities and related conditions, and clinical features at baseline among On-Label Persisters and All Persisters
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As of March 31, 2023, the registry included 68 private and academic clinical sites with 76 rheumatologists throughout 30 states and had enrolled 5996 patients, of whom 4969 (82.9%) had PsA. The registry dataset utilized for the current analyses includes these 4969 participating patients with PsA, representing 13,530.6 patient-years of follow-up and mean/median follow-up times since enrollment of 3.6/2.9 years, respectively.

This study was performed in accordance with the Declaration of Helsinki and the Guidelines for Good Pharmacoepidemiology Practice. All participating investigators were required to obtain full governing board approval for conducting noninterventional research involving humans with a limited dataset. Sponsor approval and continuing review were obtained through a central Institutional Review Board (IRB), the New England Independent Review Board (no. 120160939). For academic investigative sites that did not receive authorization to use the central IRB, full board approval was obtained from their respective governing IRBs, and documentation of approval was submitted to CorEvitas, LLC (Waltham, MA, USA) before the site’s participation and initiation of any study procedures. All patients provided written informed consent and authorization before participating.

Assessments The baseline visit was defined as the CorEvitas PsA/SpA Registry visit associated with guselkumab initiation. For patients who initiated guselkumab during a clinical visit, that visit was considered the baseline visit. For patients who initiated guselkumab between clinical visits, the prior visit was considered the baseline visit if it occurred ≤ 4 months before initiation. If the prior visit occurred > 4 months before guselkumab initiation, the first subsequent visit after initiation was considered the baseline visit if it occurred ≤ 1 month after therapy start. Otherwise, patients were excluded from this analysis. The 6-month follow-up visit was the registry visit within a 5- to 9–month window after guselkumab initiation.

For these analyses, PsA clinical features evaluated included times since PsA symptom onset and diagnosis, tender (TJC; 0–68) and swollen (SJC; 0–66) joint counts, PGA of arthritis (visual analog scale [VAS] 0–100) [14, 15], PGA of arthritis and psoriasis (VAS 0–100) [14], patient-reported pain (VAS 0–100; minimally important improvement defined as 10 points [16]), dactylitis count (0–20) [17], Leeds Enthesitis Index (LEI; 0–6) [18], and Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index (0–16) [19]. Psoriasis assessments included psoriasis diagnosis, percent body surface area with psoriasis (%BSA), and Investigator’s Global Assessment (IGA; 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe) of psoriasis [20] among patients with a history of psoriasis (prior or current), as well as nail psoriasis VAS (0–100) among patients with nail involvement. The presence of axial involvement (axial PsA) was determined by the physician using criteria detailed in Supplementary Material Table 2.

Table 2 Previous and current PsA medication use at baseline among On-Label Persisters and All Persisters
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Composite measures of disease activity included the clinical Disease Activity Index for PsA (cDAPSA), the Clinical Disease Activity Index (CDAI), and the modified Routine Assessment of Patient Index Data 3 (RAPID3). A cDAPSA score (calculated using 0–68 TJC, 0–66 SJC, patient global assessment [PtGA] of arthritis [0–10], and patient-reported pain [0–10]) ≤ 4 indicates remission, and scores > 4 to ≤ 13, > 13 to ≤ 27, and > 27 indicate low, moderate, and high disease activity, respectively [21]. A CDAI score (calculated based on 0–28 TJC, 0–28 SJC, PtGA of arthritis [0–10], and PGA of arthritis [0–10]) ≤ 2.8 indicates remission and scores > 2.8 to ≤ 10, > 10 to ≤ 22, and > 22 indicate low, moderate, and high disease activity, respectively [22]. The modified RAPID3 is derived from the Modified Multidimensional Health Assessment Questionnaire, PtGA of arthritis (0–10), and patient-reported pain (0–10) [23, 24].

Achievement of minimal disease activity (MDA) or very low disease activity (VLDA) disease states required meeting ≥ 5 or all 7, respectively, of the following criteria: TJC ≤ 1, SJC ≤ 1, BSA with psoriasis ≤ 3%, patient-reported pain (0–100) ≤ 15, PtGA of arthritis and psoriasis (0–100) ≤ 20, Health Assessment Questionnaire-Disability Index [25] ≤ 0.5, and tender entheseal points ≤ 1 [26]. Supplementary Material Table 2 provides additional details on outcomes.

Statistical Analyses

Analysis populations The study population included registry participants who initiated guselkumab on or after October 20, 2018 and had a 6-month follow-up visit on or before March 31, 2023. The primary analysis population was defined as patients who received the FDA-approved guselkumab dosing regimen for patients with active PsA (i.e., after July 13, 2020; 100 mg administered subcutaneously at weeks 0, 4, and every 8 weeks thereafter [8]) and persisted with this dosing regimen through the 6-month visit (On-Label Persisters). To support the reliability and generalizability of findings, a sensitivity analysis was conducted in a cohort of All Persisters, defined as all patients who initiated guselkumab, regardless of date or dosing regimen, and had persistent use reported at the 6-month visit.

Primary, secondary, and exploratory outcomes The primary outcome was mean (95% confidence interval [CI]) change in cDAPSA score from baseline at 6 months. Secondary outcomes (in order of multiplicity-controlled testing) were change from baseline at 6 months in PGA of arthritis and psoriasis, patient-reported pain, and %BSA among patients with a history of psoriasis (prior or current) at baseline.

Prespecified exploratory outcomes were mean change from baseline at 6 months in CDAI, modified RAPID3, and PGA of arthritis scores among all patients, and in nail psoriasis VAS score, dactylitis count, LEI score, and SPARCC Enthesitis Index score among patients with respective baseline scores > 0. Additional outcomes at 6 months included achievement of: cDAPSA or CDAI low disease activity (LDA)/remission among patients with cDAPSA or CDAI moderate-to-high disease activity, respectively, at baseline; IGA 0/1 among patients with a score ≥ 2 at baseline; IGA 0 among patients with a score ≥ 1 at baseline; MDA/VLDA response among patients not in MDA/VLDA at baseline; and < 3% BSA among patients with ≥ 3% BSA affected at baseline.

Data analyses Patient characteristics at baseline and clinical features and outcomes at baseline and 6 months were summarized using means and standard deviations (SDs) and/or medians and interquartile ranges for continuous variables and numbers and proportions of patients for categorical or ordinal variables. Clinical features, outcomes at 6 months, and mean (95% CI) changes from baseline at 6 months in continuous clinical features and outcomes were determined among patients with evaluable data at both timepoints. Paired t tests determined whether changes in continuous outcomes from baseline at 6 months were statistically significantly different from 0 (α = 0.05). Generalized McNemar testing was utilized for categorical outcomes; a single proportion, one-sided test was used to calculate p values testing the null hypothesis that the proportion of patients achieving response at 6 months is equal to 0%. Data analyses were performed using Stata 16 (College Station, TX, USA).

A fixed-sequence statistical strategy was employed to control for multiplicity, whereby the primary and secondary outcomes were tested in a predefined order, each at α = 0.05, moving within each outcome family (primary and secondary) to a subsequent outcome only after success (p < 0.05) of the previous outcome. After evaluation of the primary outcome (cDAPSA), PGA of arthritis and psoriasis, patient-reported pain, and %BSA were tested in sequence. All further exploratory outcomes were evaluated in random order without multiplicity controls. As such, the unadjusted (nominal) p values reported for such outcomes should be interpreted as supportive only.

Results

Patient disposition

Of the 329 patients with PsA enrolled in the CorEvitas PsA/SpA Registry who initiated guselkumab at or after enrollment, 133 had eligible baseline and 6-month follow-up visits as of March 31, 2023 (All Initiators) (Fig. 1), while 196 did not. Of the 133 All Initiators, 104 (78.2%) had persistent guselkumab use at 6 months (All Persisters). Among the 29 patients who discontinued guselkumab before the 6-month visit (Non-Persisters), three had a reduction in therapy (discontinued guselkumab in combination with another therapy and continued the alternate monotherapy), eight stopped therapy, and 18 switched from guselkumab to another therapy. Reasons provided by treating rheumatologists for discontinuation of guselkumab therapy included inadequate initial response (n = 10), failure to maintain initial response (n = 4), and minor side effect (n = 3) (Fig. 1).

Fig. 1
figure 1

Flowchart of selection of analysis populations. *A subset of patients who initiated guselkumab after United States FDA approval for active psoriatic arthritis and received the FDA-approved dosing regimen. **As characterized at the time of documentation. FDA Food and Drug Administration

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Of the 133 All Initiators, 114 received guselkumab on-label (after FDA approval for active PsA and at the approved dosing regimen). In this subset of 114 On-Label Initiators, 90 (78.9%) had persistent guselkumab use at 6 months (On-Label Persisters; Fig. 1). The majority of On-Label Persisters (82/90; 91.1%) initiated guselkumab at their baseline visit, while 8.9% (8/90) initiated guselkumab between visits and had a baseline visit within 4 months prior to through 1 month after initiation. Of the remaining 19 All Initiators, three started guselkumab after FDA approval for psoriasis but prior to approval for PsA, four received a non-FDA-approved guselkumab dosing regimen (100-mg dose every 13 weeks), and 12 did not have sufficient information available to determine the dosing regimen received.

Patient demographics and clinical characteristics

Among the 90 On-Label Persisters comprising the primary analysis cohort, mean (SD) age at baseline was 55.2 (12.5) years; the majority were female (69.7%), White (91.1%), and had a body mass index ≥ 30 kg/m2 (63.6%). The most prevalent comorbidities were hypertension (32.2%), fibromyalgia (23.3%), depression (22.2%), and diabetes (20.0%). Three patients had related conditions of inflammatory bowel disease (IBD, i.e., Crohn’s disease, ulcerative colitis, possible IBD, and/or other IBD), and one had uveitis (Table 1).

At baseline, on average, patients had longstanding, treatment-resistant disease that was active across PsA domains (Table 1). Among On-label Persisters, mean (SD) durations since PsA symptom onset and diagnosis were 13.6 (11.2) and 8.9 (7.9) years, respectively. Most (92.2%) patients were b/tsDMARD-experienced, with 18.9 and 73.3% having previously received one or at least two b/tsDMARDs, respectively, and 73.3, 70.0, and 44.4% having previously received at least one TNFi, non-TNFi bDMARD, or tsDMARD, respectively (Table 2).

Despite prior use of multiple advanced therapies by most On-label Persisters, moderate overall disease activity was observed at baseline, as indicated by mean (SD) cDAPSA and CDAI scores of 22.0 (15.1) and 15.8 (9.8), respectively, as well as 71.8 and 67.1% of patients, respectively, exhibiting cDAPSA and CDAI moderate-to-high disease activity (Table 3). Consistently, guselkumab was initiated due to active disease in 83.3% of these patients (reasons for initiating guselkumab and discontinuing prior therapy are summarized in Table 2). In total, 70.0% of patients received guselkumab as monotherapy.

Table 3 Disease activity measures at baseline among On-Label Persisters and All Persisters
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Regarding specific disease domains, 85.1% (74/87) and 47.1% (41/87) of patients had actively tender (mean [SD] 10.2 [12.1]) and swollen (5.0 [4.5]) joints at baseline; mean (SD) PGA of arthritis and psoriasis and patient-reported pain scores were 42.3 (23.7) and 57.0 (24.6), respectively. Twelve (13.3%) patients had a dactylitis count > 0 (mean [SD] 2.6 [1.8]). An LEI or SPARCC Enthesitis Index score > 0 was reported for 25 (28.7%) and 33 (36.7%) patients, respectively, with respective mean (SD) scores of 2.3 (1.4) and 3.5 (2.9). Axial PsA was identified in 40.0% of patients. Among On-Label Persisters with prior or current psoriasis, 49.4% (42/85) had ≥ 3% BSA affected by psoriasis, with a mean of 14.5% BSA affected. Additionally, among patients with prior or current psoriasis, 63.1% (53/84) had an IGA score ≥2 (representing mild-to-severe skin disease) and 41.2% (35/85) had a nail psoriasis VAS score > 0 (mean [SD] 19.9 [17.8]) (Table 1).

Patient demographics and clinical characteristics of All Persisters were generally consistent with those of On-Label Persisters (Tables 1, 2, and 3). Relative to All Persisters, Non-Persisters had a higher prevalence of axial involvement and history of fibromyalgia, a lower mean TJC, a lower proportion of patients with private healthcare insurance, shorter mean duration of most recent prior PsA therapy, and less extensive nail psoriasis at baseline (Supplementary Material Table 3).

Primary analysis of effectiveness—On-Label Persisters

Among On-Label Persisters, the mean cDAPSA score was significantly decreased from 21.6 at baseline to 16.1 at 6 months (mean change [95% CI]: − 5.4 [− 8.5, − 2.3]; p < 0.001) (Fig. 2A). Significant mean improvements in PGA of arthritis and psoriasis (− 19.0 [− 24.2, − 13.8]; p < 0.001), patient-reported pain (− 9.1 [− 14.4, − 3.8]; p < 0.001), and %BSA (− 5.1 [− 7.6, − 2.7]; p < 0.001) were observed at 6 months (Fig. 2A).

Fig. 2
figure 2

Mean change (95% confidence interval) from baseline at 6 months in multiplicity-controlled primary (cDAPSA) and major secondary (PGA of arthritis and psoriasis, patient-reported pain, %BSA) endpoints among On-Label Persisters (A) and All Persisters (B). aRemission = cDAPSA ≤ 4, low disease activity = cDAPSA > 4 to ≤ 13, moderate disease activity = cDAPSA > 13 to ≤ 27, high disease activity = cDAPSA > 27. bPGA ≤ 20 mm (0–100 VAS) considered minimal disease activity. cAmong patients with prior or current psoriasis. Mild = BSA < 3%, moderate = BSA ≥ 3% to ≤ 10%, severe = BSA > 10%. dPatient-reported pain score ≤ 15 mm (0–100 VAS) considered minimal pain; minimally important improvement = improvement ≥ 10 mm (VAS). %BSA percent of body surface area with psoriasis, cDAPSA clinical Disease Activity Index for Psoriatic Arthritis, PGA Physician Global Assessment, VAS visual analog scale

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Prespecified exploratory outcomes also improved from baseline at 6 months in the primary analysis of On-Label Persisters (Table 4). Mean (95% CI) improvement in PGA of arthritis was − 15.4 (− 19.9, − 10.8; nominal p < 0.001). Overall disease activity improvement was also demonstrated by mean (95% CI) decreases in CDAI (− 4.3 [− 6.7, − 2.0; nominal p < 0.001]) and modified RAPID3 (− 0.6 [− 0.9, − 0.3; nominal p < 0.001]) scores. Among patients with enthesitis at baseline, mean (95% CI) change was − 1.6 (− 2.2, − 1.0; nominal p < 0.001) for LEI and − 1.9 (− 3.1, − 0.7; nominal p = 0.002) for SPARCC Enthesitis Index scores. Of the 12 patients with a dactylitis count > 0 at baseline, six achieved resolution by 6 months (data not shown), with a mean (95% CI) change of − 1.5 (− 3.8, 0.8; nominal p = 0.17). Mean (95% CI) reduction in nail psoriasis VAS score among patients with a score > 0 at baseline was − 11.0 (− 17.6, − 4.4; nominal p = 0.002).

Table 4 Mean change in exploratory clinical outcomes from baseline at 6 months among On-Label Persisters and All Persisters
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Additionally, among patients with cDAPSA or CDAI moderate-to-high disease activity at baseline, 25.0% (13/52; 95% CI: 14.0%, 38.9%) achieved cDAPSA LDA/remission and 32.0% (16/50; 95% CI: 19.5%, 46.7%) achieved CDAI LDA/remission, respectively, at 6 months. An IGA 0/1 score was achieved at 6 months by 51.0% (26/51; 95% CI: 36.6%, 65.2%) of patients with a score ≥ 2 at baseline, IGA 0 score was achieved by 29.5% (18/61; 95% CI: 18.5%, 42.6%) of patients with a score ≥ 1 at baseline, and BSA with psoriasis < 3% was achieved by 58.5% (24/41; 95% CI: 42.1%, 73.7%) of patients with ≥ 3% BSA affected at baseline (Fig. 3). Mean changes in %BSA affected by psoriasis were − 6.6 (95% CI: − 9.6, − 3.7) in the 63 patients with > 0 BSA affected at baseline and − 10.0 (95% CI: − 14.3, − 5.8) in 41 patients with ≥ 3% BSA affected at baseline. Among patients not in MDA/VLDA at baseline, 21.5% (14/65; 95% CI: 12.3%, 33.5%) achieved MDA/VDLA at 6 months (Fig. 3).

Fig. 3
figure 3

Change in disease state and disease activity categories from baseline at 6 months among On-Label Persisters (A) and All Persisters (B). *Nominal p < 0.001. aAmong patients with moderate/high disease activity at baseline (cDAPSA > 13). bAmong patients with moderate/high disease activity at baseline (CDAI > 10). cAssessed in patients with prior or current psoriasis. dAmong patients with ≥ 3% BSA affected by psoriasis at baseline. eAmong patients with baseline IGA score ≥ 2. fAmong patients with baseline IGA score ≥ 1. gAmong patients not in MDA/VLDA at baseline. BSA body surface area, CDAI Clinical Disease Activity Index, cDAPSA clinical Disease Activity Index for Psoriatic Arthritis, CI confidence interval, IGA Investigator’s Global Assessment, LDA low disease activity, MDA minimal disease activity, REM Remission, VLDA very low disease activity

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Sensitivity analysis of effectiveness—All Persisters

Consistent with effectiveness observed in On-Label Persisters, mean (95% CI) improvements were observed in All Persisters for cDAPSA (− 4.9 [− 7.6, − 2.1; nominal p < 0.001]), PGA of arthritis and psoriasis (− 17.0 [− 21.8, − 12.2; nominal p < 0.001]), patient-reported pain (− 7.6 [− 12.6, − 2.6; nominal p = 0.004]), and %BSA (− 4.8 [− 7.1, − 2.5; nominal p < 0.001]) (Fig. 2B). Overall disease activity improved, as demonstrated by mean (95% CI) decreases in composite disease activity scores (CDAI: − 3.9 [− 6.0, − 1.8], nominal p < 0.001 and modified RAPID3: − 0.5 [− 0.8, − 0.2], nominal p = 0.002) (Table 4). Improvements in PGA of arthritis, dactylitis, and enthesitis (Table 4), as well as the proportions of All Persisters achieving cDAPSA and CDAI LDA, IGA 0/1, IGA 0, < 3% BSA, and MDA/VLDA, at 6 months were comparable to those in the On-Label Persisters (Fig. 3).

Discussion

In a previous report characterizing patients with PsA in the CorEvitas PsA/SpA Registry, a cohort of patients who initiated guselkumab for PsA was observed to have active peripheral joint and skin disease and substantial pain [13]. Here we describe real-world effectiveness of guselkumab in a cohort of registry participants who initiated on-label guselkumab treatment and had persistent use at their 6-month follow-up visit, a population generally characterized by longstanding, treatment-resistant, active PsA at the time of guselkumab initiation.

Among On-Label Initiators with a 6-month follow-up visit, nearly 80% continued treatment through the 6-month visit. This finding is consistent with the high retention rates of guselkumab-randomized patients in the phase 3, placebo-controlled trials of guselkumab in patients with active PsA, including TNFi-IR patients, through 1 year of DISCOVER-1 (94%) [27] and COSMOS (88%) [12] and through 2 years of DISCOVER-2 (90%) [28, 29]. High guselkumab persistence at 2 years (84%) was also observed in a retrospective study conducted in Spain evaluating 90 patients who initiated guselkumab for PsA or psoriasis in clinical practice [30]. In a more limited real-world observational Italian cohort of 24 patients with early PsA and extensive skin involvement who initiated guselkumab, more than two-thirds continued treatment through 1 year [31]. Furthermore, among patients with psoriasis, including those with concurrent PsA, enrolled in the British Association of Dermatologists Biologic and Immunomodulators Register, guselkumab had the highest drug survival that was associated with effectiveness over 2 years of the biologics evaluated [32]. Consistently, in a recent claims database analysis of biologic-naïve and biologic-experienced patients with psoriasis who initiated treatment with guselkumab, adalimumab, secukinumab, or ixekizumab, persistence over 24 months was highest for those receiving guselkumab [33].

In the current analysis of patients with persistent on-label guselkumab use, 92% previously received at least one b/tsDMARD at baseline. Seventy percent of patients received guselkumab as monotherapy. Most (93%) patients in the Spanish cohort who received guselkumab for PsA or psoriasis in clinical practice were also biologic-experienced [30]. Of note, clinical response rates in the DISCOVER and COSMOS trials were generally consistent between patients who received guselkumab as monotherapy (37–47%) and those reporting concomitant methotrexate use (53–63%) [10,11,12].

On average, our study cohort of On-Label Persisters exhibited active PsA across multiple domains at baseline, as demonstrated by assessments of peripheral and axial joint disease, skin and nail psoriasis, enthesitis, and dactylitis, with 72% having moderate-to-high disease activity assessed by cDAPSA. These characteristics are generally consistent with the aforementioned Spanish cohort, although only 48% of those patients had DAPSA moderate-to-high disease activity and a greater proportion (24 vs. 13%) had dactylitis [30].

The current cohort of patients with active PsA and persistent on-label guselkumab use exhibited significant mean improvements from baseline at 6 months in peripheral joint arthritis, pain, and skin disease, as measured by cDAPSA, PGA of arthritis and psoriasis, patient-reported pain, and %BSA; findings were largely consistent with those observed in the sensitivity analysis population of All Persisters. Improvements were also observed in exploratory outcomes evaluating other PsA disease domains, including enthesitis and skin and nail disease, as well as by mean changes in CDAI, an instrument utilized predominantly in clinical practice to assess overall disease activity [22]. Furthermore, 22% of the patients in the primary analysis cohort who did not meet MDA/VLDA criteria at baseline achieved this stringent outcome at 6 months, which is in line with the 15–30% MDA/VLDA response rates observed with 6 months of guselkumab treatment in clinical trials [10,11,12]. Achievement of minimal levels of disease activity is an important outcome [34] that has been shown to be associated with low rates of radiographic progression [35] and long-term improvements in health-related quality of life and functional ability [35, 36]. Specific to guselkumab, results of a recent analysis from the 2-year DISCOVER-2 study, which enrolled bio-naïve patients with active PsA and an elevated risk of future structural damage, showed that patients with active PsA receiving guselkumab who achieved low levels of disease activity (including MDA) generally had lower rates of radiographic progression, on average, than patients who did not achieve these treatment targets [37]. Patients in the real-world Spanish and Italian cohorts who received guselkumab for PsA also realized significant improvements in articular and skin manifestations at 6 months [30, 31].

Although dactylitis was present in a minority of patients at baseline (13%), six of these 12 achieved resolution by 6 months. In the larger DISCOVER-1 (mixed population), DISCOVER-2 (biologic-naïve), and COSMOS (TNFi-IR) trials, 65, 59, and 45% of patients with baseline dactylitis, respectively, achieved resolution with 6 months of guselkumab treatment [10,11,12].

The clinical effectiveness of guselkumab reported herein supports the efficacy demonstrated at the primary endpoint (week 24) in the phase 3, randomized, placebo-controlled trials of guselkumab conducted in biologic-naïve and TNFi-experienced adults with active PsA [10,11,12]. The magnitude of effect size with guselkumab observed in the present study—among patients who were primarily bDMARD-experienced (including TNFi)—is consistent with a separate analysis of PsA patients in the CorEvitas PsA/SpA Registry showing a higher likelihood of achieving clinical outcomes, including MDA, after 6 months of treatment among patients who switched from a first-line TNFi to a non-TNFi than in those who cycled to an alternate TNFi [38].

The real-world setting of the CorEvitas PsA/SpA Registry allows for comprehensive analyses of patient-level data captured by rheumatologists across the US. Additionally, it is noteworthy that in this real-world analysis, the primary and major secondary endpoints were controlled for multiplicity. While the findings of the current analysis may not be generalizable to patients outside the US, participants in this registry may be more representative of the general population of patients with PsA considering biologic therapy than the more homogeneous populations of clinical trials.

As potential limitations, patient selection based on guselkumab persistence at a 6-month follow-up visit (within a 5- to 9-month window) may introduce time and selection biases. While some differences were noted in baseline patient characteristics between All Persisters and Non-Persisters, they should be interpreted with caution due to the small sample size of Non-Persisters and the limited details available regarding end of treatment exposure. Persistence at 6 months was confirmed for patients in the On-Label Persisters cohort; however, a small subset of Non-Persisters who reported stopping guselkumab treatment close to the 6-month visit date may have continued to be exposed to guselkumab at the 6-month follow-up visit. Also, the lack of precision in the reporting of some dates (i.e., month and year only) may have affected the determination of visit windows. Findings derived from exploratory outcomes may also be limited by small sample sizes and lack of multiplicity control in statistical testing. Furthermore, this study focused on the effectiveness of guselkumab assessed via primary, secondary, and composite outcomes with reliance on physician-reported assessments, which may be discordant with patients’ perception of their disease activity [39]. Details of patient-reported outcome measures at guselkumab initiation and after 6 months of treatment will be reported in a forthcoming publication to further assess the effectiveness of guselkumab in reducing disease burden in these patients. While 6 months is an adequate follow-up period to assess initial response to therapy, longer-term evaluations are needed to assess the durability of the effectiveness of guselkumab; as such an evaluation through 12 months of persistent guselkumab use in this patient population is planned. In the interim, it is reassuring that response rates determined using nonresponder imputation among guselkumab-treated patients were sustained or increased through the completion of the 1-year DISCOVER-1 [27] and COSMOS [12] studies and the 2-year DISCOVER-2 study [28, 29].

Although safety data were not prospectively assessed in these analyses, three patients who discontinued guselkumab did so owing to a “minor side effect.” In large, randomized, placebo-controlled studies, guselkumab has been shown to exhibit a positive benefit–risk profile through up to 2 years in patients with active PsA [40, 41], with a safety profile consistent with placebo (through approximately 6 months) and that observed with up to 5 years of guselkumab treatment in patients with moderate-to-severe plaque psoriasis [42].

Conclusions

This is among the first studies to capture real-world guselkumab effectiveness data in patients with generally treatment-resistant active PsA seen in routine clinical practice in the US. Significant improvements in peripheral joint disease, skin disease activity, and patient-reported pain were observed in primarily biologic-experienced patients with 6 months of persistent on-label guselkumab use. These data support the efficacy of guselkumab demonstrated in phase 3, randomized, placebo-controlled trials and offer valuable insights on the effectiveness of guselkumab in the routine care of patients with PsA.