# Guselkumab Provides Durable Improvement Across Psoriatic Arthritis Disease Domains: Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo Controlled Study

Laura Coates, Laure Gossec, Miriam Zimmermann, May Shawi, Emmanouil Rampakakis, Natalie Shiff, Alexa Kollmeier, Xie Xu, Peter Nash, Philip Mease, et al.

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Laura Coates, Laure Gossec, Miriam Zimmermann, May Shawi, Emmanouil Rampakakis, et al. "Guselkumab Provides Durable Improvement Across Psoriatic Arthritis Disease Domains: Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo Controlled Study." RMD Open, 2024, 10 (1), pp.e003977. 10.1136/rmdopen-2023-003977. hal-04977912

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Title:

Guselkumab Provides Durable Improvement Across Psoriatic Arthritis Disease Domains: Post Hoc

Analysis of a Phase 3, Randomized, Double-Blind, Placebo Controlled Study

4

Authors:

Laura C. Coates, MBChB, PhD¹, Laure Gossec, MD, PhD²,³, Miriam Zimmermann, PhD⁴, May Shawi, PhD⁵,

Emmanouil Rampakakis, PhD⁶,⁷, Natalie J. Shiff, MD⁸,⁹, Alexa P. Kollmeier, MD¹⁰, Xie L. Xu, PhD¹⁰, Peter

Nash, MD¹¹, Philip J. Mease, MD¹², Philip S. Helliwell, MD¹³

9

Affiliations:

¹University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal

Sciences, Oxford, UK

²Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France

³AP-HP, Pitié-Salpêtrière Hospital, Rheumatology Department, Paris, France

⁴Immunology, Janssen Medical Affairs, LLC, Zug, Switzerland

⁵Immunology, Janssen Research & Development, LLC, Titusville, NJ, USA

⁶Department of Pediatrics, McGill University, Montreal, Canada

⁷JSS Medical Research, Inc, Scientific Affairs, Montreal, Canada

⁸Janssen Scientific Affairs, LLC, Horsham, PA, USA

⁹Department of Community Health & Epidemiology, University of Saskatchewan, Saskatoon, Canada

¹⁰Janssen Research & Development, LLC, San Diego, CA, USA

¹¹Rheumatology Research Unit, Griffith University and University of Queensland, Queensland, Australia

¹²Swedish Medical Center/Providence St. Joseph Health and University of Washington, Rheumatology

Research, Seattle, WA, USA

¹³Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK / Chapel

Allerton Hospital, UK

27

Corresponding author:

Laura C. Coates, PhD, ORCID: 0000-0002-4756-663X

laura.coates@ndorms.ox.ac.uk

ABSTRACT

Objective: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of

Psoriasis and Psoriatic Arthritis (GRAPPA)-recognized domains/related conditions of psoriatic arthritis

(PsA).

Methods: Post hoc analyses utilized data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase

inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL),

randomized (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to

guselkumab. Outcomes aligned with key GRAPPA-recognized domains of overall disease activity,

peripheral arthritis, axial disease, enthesitis/dactylitis, and skin psoriasis (nail psoriasis not assessed).

PsA-related conditions (inflammatory bowel disease [IBD]/uveitis) were assessed via adverse events.
41 Least squares mean changes from baseline through W100 in continuous outcomes employed repeated
42 measures mixed-effects models adjusting for baseline scores. Binary measure response rates were
43 determined with nonresponder imputation for missing data.

44 **Results:** 442/493 (90%) of guselkumab-randomized patients completed treatment through W100.
45 Following early reductions in disease activity with guselkumab, durable improvements were observed
46 across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through
47 W100. Response rates of therapeutically relevant targets generally increased through W100 with
48 Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis
49 61%/70%/dactylitis 72%/83% resolution, Psoriasis Area and Severity Index 100 59%/53%, Psoriatic
50 Arthritis Disease Activity Score LDA 51%/49%, and minimal disease activity 38%/40%. Through W112, no
51 cases of IBD developed among guselkumab-randomized patients and 1 case of uveitis was reported.

52 **Conclusion:** In biologic-naïve patients with active PsA, guselkumab provided early and durable
53 improvements in key GRAPPA-recognized domains through 2 years, with substantial proportions
54 achieving important treatment targets.

55 Q&A BOX

56 • What is already known on this topic

57 • Guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
58 (GRAPPA)-recommend that PsA therapy achieves lowest possible levels of disease activity
59 across six domains and two related conditions.

60 • Guselkumab, a fully human monoclonal interleukin-23p19-subunit inhibitor, has previously
61 been shown to significantly improve signs and symptoms of psoriatic arthritis (PsA) by Week
62 24, with improvements sustained or further increased through Week 52.

63 • What this study adds

64 • Treatment with guselkumab every 4 or 8 weeks provided early and durable improvements in
65 all assessed GRAPPA-recognized PsA domains through 2 years of treatment, resulting in
66 considerable proportions achieving low levels of joint disease activity, enthesitis/dactylitis
67 resolution, complete skin clearance, and low/minimal levels of overall disease activity.

68 • Through Week 100 among guselkumab-randomized patients, no exacerbation or new onset
69 of inflammatory bowel disease occurred, and a single occurrence of uveitis (iridocyclitis) was
70 reported.

71 • How this study might affect research, practice, or policy

72 • Given the multidomain nature of PsA, as well as the comprehensive and durable
73 effectiveness and favorable safety profile of guselkumab shown in the current analysis,
74 guselkumab represents an important treatment option to address key GRAPPA-recognized
75 therapeutic goals for patients with PsA.
76 INTRODUCTION

77 Psoriatic arthritis (PsA) is a clinically heterogeneous, progressive, chronic inflammatory disease involving
78 the skin and musculoskeletal systems with potential to irreversibly damage joints and impair health-
79 related quality of life (HRQoL) [1-3]. PsA affects approximately 30% of individuals with psoriasis [4] and
80 has an estimated worldwide prevalence between 0.3 and 1% [5].

81 The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recognizes six
82 disease domains (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, psoriatic nail
83 disease), two related conditions (inflammatory bowel disease [IBD] and uveitis) [6], and several
84 comorbidities (e.g., obesity, metabolic syndrome, diabetes mellitus) of PsA, all of which impact patients'
85 HRQoL [7]. Current international guidelines for PsA put forward optimizing functional status, improving
86 HRQoL, preventing structural damage, and minimizing complications both from untreated active disease
87 and from therapy as key therapeutic goals [6, 8, 9]. Furthermore, the GRAPPA guidelines specifically
88 highlight achieving the lowest possible level of disease activity across all disease domains affected in an
89 individual patient [6].

90 Guselkumab, a fully human monoclonal antibody that is an interleukin (IL)-23p19-subunit inhibitor, is
91 approved to treat adults with moderate-to-severe plaque psoriasis, as well as those with active PsA. In
92 two separate Phase 3 randomized trials (DISCOVER-1 and DISCOVER-2) in PsA, participants treated with
93 guselkumab, either every 4 (Q4W) or 8 weeks (Q8W), were reported to have significantly higher rates of
94 response or mean improvements in joint signs and symptoms, enthesitis and dactylitis, skin disease,
95 physical function, and HRQoL at Week 24 compared with the placebo group [10, 11]. In pooled analyses
96 of these studies, guselkumab provided robust and sustained benefits through 1 year of treatment as
97 measured by composite disease activity indices (including Disease Activity Index for Psoriatic Arthritis
98 [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and minimal disease activity [MDA]), which
99 incorporate multiple domains recognized by GRAPPA [12]. In the DISCOVER-2 study of biologic-naïve
100 patients with highly active PsA, improvements with guselkumab treatment were found to be durable
101 through 2 years of follow up across multiple disease domains [13].

102 Informed by the GRAPPA treatment goal of achieving the lowest possible level of disease activity in all
103 affected disease domains, in the context of minimal side effects, and knowledge that residual disease
104 burdens patients and impairs function [14], the objective of the present post hoc analysis was to
105 evaluate the long-term (Week 100) effectiveness of guselkumab across GRAPPA-identified PsA domains
106 and related conditions assessed in DISCOVER-2. These included peripheral arthritis, axial symptoms,
107 enthesitis, dactylitis, and skin disease, as well as the incidence of new onset or exacerbation of IBD and
108 uveitis.

109
## 110 METHODS

Full details of the study design and eligibility criteria for DISCOVER-2 (NCT03158285) have been reported [11]. Briefly, this was a randomized, double-blind, placebo-controlled, Phase 3 trial of guselkumab in adults with active PsA, conducted between July 2017 and November 2020. The trial was carried out at 118 sites across 13 countries in Europe, Asia, and the USA. The DISCOVER-2 study conformed with the Declaration of Helsinki and Good Clinical Practice guidelines and obtained all necessary ethics approvals.

Eligible patients had active PsA (swollen joint count [SJC] ≥5, tender joint count [TJC] ≥5, and C-reactive protein [CRP] level ≥0.6 mg/dL) and an inadequate response to, or intolerance of, standard non-biologic treatment. Patients could not have previously received biologics or Janus-kinase inhibitors. Study participants were randomized (1:1:1) to receive subcutaneous injections of guselkumab 100 mg Q4W; guselkumab 100 mg at Week 0, Week 4, then Q8W; or placebo with crossover to guselkumab 100 mg Q4W at Week 24 through Week 100.

## 122 Outcome Measures

Efficacy assessments selected for the current post hoc analysis aligned with GRAPPA-identified domains, i.e., peripheral arthritis (66-joint SJC, 68-joint TJC), axial symptoms (patient-reported spinal pain; Bath Ankylosing Spondylitis Disease Activity Index Question 2 [15]), enthesitis (Leeds Enthesitis Index [LEI] [16]), dactylitis (Dactylitis Severity Score [DSS] [17]), and skin psoriasis (Psoriasis Area and Severity Index [PASI] [18], Investigator's Global Assessment of psoriasis [IGA] [19], Patient's Assessment of Skin Disease on a Visual Analog Scale [Skin VAS]). As longitudinal nail disease assessments were not performed in DISCOVER-2, nail psoriasis was not considered in the present analysis.

Composite scores were also assessed as measures of joint and overall disease activity. Peripheral disease activity was assessed with DAPSA [20], calculated via the addition of SJC, TJC, patient assessment of arthritis disease activity on a VAS, patient assessment of joint pain on a VAS, and CRP level, as well as clinical DAPSA (cDAPSA) [21], a simplified version of DAPSA that omits CRP. PASDAS [22] is a multi-domain measure of overall disease activity that combines SJC, TJC, tender dactylitis count, LEI, serum CRP concentration, physician global assessment of disease activity, patient global assessment of disease activity, and Short Form (SF)-36 physical component summary (PCS) score. MDA [23] is defined as meeting ≥5 of the following 7 criteria: TJC ≤1, SJC ≤1, PASI ≤1, patient pain VAS ≤15, patient global assessment of disease activity on a VAS ≤20 mm, Health Assessment Questionnaire-Disability Index (HAQ-DI) score ≤0.5, and ≤1 tender enthesal points.

Continuous outcomes evaluated were changes from baseline through Week 100 in SJC, TJC, spinal pain (in patients with axial symptoms and imaging-confirmed sacroiliitis [24, 25]), LEI (in patients with baseline enthesitis), DSS (in patients with baseline dactylitis), Skin VAS and PASI (in patients with ≥3% body surface area [BSA] and IGA score ≥2 at baseline).

Achievement of therapeutic endpoints was assessed with DAPSA low disease activity (LDA; score ≤14) or remission (≤4); cDAPSA LDA (≤13) or remission (≤4); resolution of enthesitis (LEI=0) in patients with enthesitis at baseline; resolution of dactylitis (DSS=0) in patients with dactylitis at baseline; PASDAS LDA (≤3.2) or remission (≤1.9); and MDA. Skin assessments, evaluated among patients with ≥3% BSA and IGA score ≥2 at baseline, included Skin VAS ≤15 mm (among those with baseline Skin VAS >15 mm), PASI improvement ≥90% or 100% (PASI90/100), and IGA=0 or 1 with ≥2 grade improvement from baseline. Certain results presented herein, including the proportions of patients achieving MDA at Week 24, and enthesitis and dactylitis resolution, PASI90, PASI100, and IGA 0/1 response at Weeks 24, 52, and 100
152 have been previously reported [11, 13]; they are shown in this paper to provide context surrounding the
153 patterns of group-level effectiveness through Week 100.

154 Adverse events (AEs) were assessed through Week 112 of DISCOVER-2. The occurrence of IBD (defined
155 by Medical Dictionary for Regulatory Activities [MedDRA] System Organ Class preferred terms [PTs] of
156 Crohn's disease, ulcerative colitis, or IBD) and uveitis (defined by MedDRA PTs of uveitis, iridocyclitis, or
157 iritis), or their exacerbation in patients with IBD or uveitis at baseline, was determined following blinded
158 review of the reported AEs.

159 Statistical Methods

160 Analyses were limited to patients randomized to guselkumab. Least squares mean (LSM) changes from
161 baseline to available visits between Week 8 and Week 100 in SJC, TJC, spinal pain, LEI, DSS, and Skin VAS
162 were analyzed by repeated measures generalized linear mixed-effects models adjusting for respective
163 baseline score, time, guselkumab dosing regimen, and the interaction of time with guselkumab regimen.
164 Although SJC and TJC were first assessed at Week 4, Week 8 was used as the first timepoint of
165 assessment to standardize timeframes across outcome measures, except for PASI, which was first
166 evaluated at Week 16. Radar plots, reported logarithmically due to scale differences in the outcomes
167 assessed, were used to describe changes in SJC, TJC, spinal pain, LEI, DSS, and Skin VAS at each time
168 point for each guselkumab regimen. Achievement of therapeutic endpoints was summarized by
169 descriptive statistics using nonresponder imputation (NRI) for missing data applied at rates
170 approximating study discontinuations (<10%). Composite scores with missing component data were
171 imputed as non-response. The incidence/exacerbation of IBD and uveitis was summarized descriptively.
172 All analyses were performed using the Statistical Analysis System (SAS) statistical software package,
173 version 9.4 (SAS Institute Inc., Cary, NC, USA).
174 **RESULTS**

175 **Patient Disposition and Baseline Characteristics**

176 Among the 493 patients who were randomized to guselkumab in DISCOVER-2, 245 and 248 received guselkumab 100 mg Q4W and Q8W, respectively. The additional 246 patients randomized to placebo were not included in these post hoc analyses assessing long-term effectiveness. Baseline demographic and PsA disease characteristics were generally similar across the treatment groups [11].

180 **Table 1** summarizes the baseline characteristics of patients randomized to and treated with guselkumab. Mean PASDAS, DAPSA, and cDAPSA scores were consistent with highly active PsA. Approximately one-third of patients were identified by the investigator as having axial symptoms and had imaging-confirmed sacroiliitis, nearly half had dactylitis, two-thirds had enthesitis, and three-quarters had BSA ≥3% and IGA ≥2. Approximately 60% and 20% of patients reported concomitant use of methotrexate and corticosteroids, respectively, at baseline (Table 1).

186 Among patients randomized to guselkumab, 93% completed study treatment at Week 52, and 90% did so through Week 100. Patients were analyzed by intention to treat, and those who discontinued were imputed as nonresponders.

189 **Overall Patterns of Improvement**

190 Substantial mean improvements were observed as early as Week 8 for each endpoint assessed (Figure 1). A significant decrease in mean PASI score was observed with both guselkumab regimens at Week 16 (p<0.0001), the first timepoint assessed, which was subsequently maintained through Week 100. In all other PsA domains assessed, specifically SJC, TJC, spinal pain, LEI, DSS, and Skin VAS, mean improvements among patients treated with either guselkumab Q4W or Q8W were continuously enhanced through Week 100 (Figure 1; Supplemental Figure 1).

196 Similarly, therapeutic endpoint response rates increased over time in all key PsA domains and were generally maintained or continued to increase between Week 52 and Week 100 of guselkumab treatment, regardless of dosing regimen (Table 2). Adding to the considerable improvements between baseline and the first analysis timepoint, notable increases in endpoint response rates between consecutive visits were also observed later in the follow-up period. For most endpoints assessed, in one or both guselkumab regimens, the between-timepoint increase in response rate was highest or second highest for the period between Week 24 and Week 52 (Table 2).

203 **Arthritis Improvement**

204 For both guselkumab regimens, significant reductions in SJC and TJC were observed by Week 8 (all p<0.0001), the first analysis timepoint, and improvements at the group level continued through Week 100 (Figure 1; Supplemental Figure 1). In patients receiving guselkumab Q4W, the LSM changes from baseline to Week 24 and Week 100, respectively, were -8.4 and -10.4 for SJC and -11.2 and -15.5 for TJC. The same pattern was seen in Q8W-randomized patients at Week 24 and Week 100, with LSM changes of -8.4 and -10.3 for SJC and -10.9 and -15.5 for TJC, respectively (Figure 1). These improvements represent 69%-88% reductions in the mean joint scores by Week 100.

211 **Skin Psoriasis Improvement**

212 For both skin assessments (Skin VAS and PASI), a significant improvement was seen in patients with ≥3% BSA and IGA score ≥2 at baseline at the first timepoint of assessment (Weeks 8 and 16, respectively;
214 both p<0.0001; **Figure 1**). With both guselkumab regimens, mean improvements in Skin VAS continued
215 through Week 100 and the significant mean decreases in PASI scores recorded as of the first assessment
216 timepoint were maintained through Week 100 (**Figure 1; Supplemental Figure 1**).

217 Among Q4W-randomized patients, the respective LSM changes from baseline to Week 24 and Week 100
218 were -39.0 and -46.1 for Skin VAS and -12.1 and -12.7 for PASI. Similarly, in Q8W-randomized patients,
219 changes averaged -39.8 and -47.2 for Skin VAS and -12.0 and -12.4 for PASI at these timepoints (**Figure
220 1**). Overall, these results indicate a 72%-96% improvement in symptoms of skin psoriasis by Week 100.
221 Achievement of PASI90 response by patients receiving guselkumab Q4W and Q8W (54% and 55% at
222 Week 16, 77% and 74% at Week 52, respectively) and IGA score of 0 or 1 and a ≥2 grade improvement
223 (66% and 62% at Week 16, 80% and 74% at Week 52, respectively) showed consistent durability of
224 response across guselkumab dosing regimens and was maintained through Week 100 (**Table 2**).
225 Between Week 16 and Week 100, the proportion of patients achieving skin clearance (PASI100)
226 increased by 25% and 26% with guselkumab Q4W and Q8W, respectively (**Table 2**).

227 Among patients with Skin VAS >15 mm, IGA ≥2, and BSA ≥3% at baseline, achievement of Skin VAS ≤15
228 mm was seen in 14% and 22% of patients receiving Q4W and Q8, respectively, by Week 8; by Week 100,
229 53% and 56% of patients receiving each regimen achieved minimal skin involvement, respectively (**Table
230 2**).

231 **Spinal Pain Improvement**

232 Among patients with axial symptoms in the guselkumab Q4W (33%) and Q8W (27%) groups, significant
233 improvement in spinal pain was recorded as of Week 8 (first timepoint assessed; p<0.0001). Between
234 subsequent follow-up visits through Week 100, mean improvements were either maintained or further
235 enhanced (**Figure 1 & Supplemental Figure 1**). The respective LSM changes in spinal pain from baseline
236 to Week 24 and Week 100 were -2.3 and -3.0 among patients treated with guselkumab Q4W and -2.6
237 and -3.3 for those receiving the Q8W regimen, representing 46%-50% improvement by Week 100
238 (**Figure 1**).

239 **Enthesitis and Dactylitis Improvement**

240 Among patients with baseline enthesitis (Q4W: 69%; Q8W: 64%) and those with baseline dactylitis
241 (Q4W: 49%; Q8W: 45%), significant improvements in both enthesitis and dactylitis were recorded as of
242 the first follow-up assessment at Week 8 (both p<0.0001), regardless of guselkumab regimen. Mean
243 improvements were either maintained or further increased between subsequent follow-up visits
244 through Week 100 (**Figure 1; Supplemental Figure 1**).

245 In affected patients randomized to the Q4W regimen, the respective LSM changes from baseline to
246 Week 24 and Week 100 were -1.6 and -2.1 for LEI and -6.5 and -7.5 for DSS. Consistent improvements
247 were seen in Q8W-randomized patients, with respective LSM changes from baseline to Week 24 and
248 Week 100 of -1.7 and -2.2 for LEI and -6.2 and -7.9 for DSS (**Figure 1**).

249 Among patients with enthesitis as baseline, the proportions of patients achieving enthesitis resolution
250 (LEI=0) increased continuously through Week 100 in both guselkumab groups, whereby response rates
251 were 27% and 32% at Week 8, 56% and 62% at Week 52, and 61% and 70% at Week 100 for guselkumab
252 Q4W and Q8W, respectively (**Table 2**).

253 Proportions of patients achieving dactylitis resolution (DSS=0), among those with baseline dactylitis,
254 increased through Week 52 and were then maintained or continued to improve through Week 100
255 (32%, 74%, and 72% at Week 8, 52, and 100 with guselkumab Q4W and 31%, 77%, and 83% with guselkumab Q8W; **Table 2**).

257 **Composite Responses**

258 Despite mean composite scores indicative of high disease activity at baseline, NRI response rates for DAPSA LDA/remission, cDAPSA LDA/remission, PASDAS LDA/remission, and MDA increased continuously through Week 100, regardless of guselkumab regimen (**Table 2**). More precisely, among patients in the Q4W group, respective Week 8, Week 24, Week 52, and Week 100 response rates for DAPSA LDA/remission were 18%/2%, 36%/9%, 51%/16%, and 62%/21%; for PASDAS LDA/remission were 10%/2%, 24%/9%, 43%/15% and 51%/21%, and MDA were 3%, 19%, 34%, and 38%. A similar pattern of achievement was seen with the Q8W dosing regimen, with response rates at Week 8, Week 24, Week 52, and Week 100 of 17%/1%, 39%/9%, 52%/19%, and 59%/24% for DAPSA LDA/remission; 11%/1%, 31%/9%, 43%/21%, and 49%/23% for PASDAS LDA/remission; and 4%, 25%, 31%, and 40% for MDA, respectively. Results for cDAPSA were comparable to those obtained for DAPSA for both guselkumab regimens (**Table 2**).

269 **PsA-related Conditions**

270 Among guselkumab-randomized patients, 1 patient had a history of IBD and 4 had a history of uveitis; none of these patients experienced an AE of exacerbation of these conditions through Week 100. 271 Furthermore, through Week 100, no guselkumab-randomized patient developed IBD. One case of 272 uveitis was reported (Q8W group; Week 70) that resolved following treatment with steroid and 273 nonsteroid anti-inflammatory drugs with no changes to guselkumab dosing. 274
275

DISCUSSION

276 Previous analyses of the Phase 3 DISCOVER-1 and DISCOVER-2 studies have demonstrated that, compared with placebo, treatment with guselkumab was associated with significantly greater improvements in signs and symptoms of PsA by Week 24 [10, 11] and that these improvements were sustained through Week 52 [26, 27] and, in DISCOVER-2, Week 100 [13]. In the current post hoc analysis of DISCOVER-2 data, both guselkumab regimens provided both early significant improvements and continuously increasing response rates through Week 100 in key GRAPPA-identified domains. The robust improvements in skin disease seen in these PsA patients were highly durable over time. Importantly, early significant improvements in peripheral arthritis, dactylitis, enthesitis, and axial symptoms were also enhanced and durable over time. Following the considerable improvements between baseline and the first analysis timepoint (Week 8, except for PASI [Week 16]), both joint and skin response rates were further increased at 1 year. Furthermore, the substantial increases in overall disease response rates (PASDAS LDA and MDA) as well as achievement of remission targets (cDAPSA/DAPSA and PASDAS) generally found at 1 year were sustained through 2 years.

289 Regardless of guselkumab dosing regimen, considerable proportions of patients achieved disease control across domains at Week 100. Specifically, approximately 60% of guselkumab-randomized patients reached low levels of joint disease activity as defined by either DAPSA or cDAPSA; 61%-83% achieved enthesitis or dactylitis resolution; 53%-76% achieved almost clear or clear skin as indicated by PASI90, PASI100, or IGA scores of 0 or 1 and a ≥2 grade improvement from baseline; approximately 50% achieved PASDAS LDA; and 38%-40% achieved MDA. In patients with axial symptoms and imaging-confirmed sacroiliitis, spinal pain was diminished by nearly 50% on average. Overall, findings were in agreement with previous guselkumab trials in psoriasis patients demonstrating substantial and durable improvement in skin disease [28] and with a network meta-analysis of data from randomized controlled trials [29] of patients with PsA that found guselkumab provides comparable joint disease efficacy and superior skin disease efficacy relative to other advanced PsA treatments.

300 Although nail disease, an important GRAPPA-identified domain, was not assessed in DISCOVER-2, a post hoc analysis of pooled data from the VOYAGE-1 and -2 studies of patients with moderate-to-severe psoriasis found that, among patients with fingernail psoriasis, guselkumab-treated patients achieved clearance of or minimal fingernail psoriasis in significantly higher proportions by Week 16 than those receiving placebo [30]. Furthermore, a subgroup analysis of VOYAGE-1 and -2 patients with self-reported PsA also found that, compared with placebo, a significantly greater proportion of guselkumab-treated patients saw improvements in nail, scalp, and palmoplantar psoriasis by Week 16 [31].

307 In addition to achieving the lowest possible level of disease activity in all disease domains affected, the GRAPPA, American College of Rheumatology (ACR)/National Psoriasis Foundation and European Alliance of Associations for Rheumatology (EULAR) treatment guidelines promote optimizing functional status, improving HRQoL, preventing structural damage, and minimizing complications both from untreated active disease and from therapy [6, 8, 9, 32]. Analyses of the DISCOVER-1 and -2 studies through Week 24 found that both guselkumab dosing regimens were associated with significant improvements versus placebo in physical function and HRQoL, as measured by the HAQ-DI and SF-36 PCS scores, respectively, as well as numerical improvements in SF-36 mental component summary (MCS) score [10, 11]. Importantly, these improvements by Week 24 were sustained or continued through Week 52 [26, 27] and, in DISCOVER-2, through Week 100 [13]. Furthermore, in DISCOVER-2, which included imaging assessments, patients treated with guselkumab demonstrated less radiographic progression relative to placebo at Week 24, with this effect reaching statistical significance in the Q4W group [11]. Regardless of guselkumab dosing regimen, low rates of radiographic progression were maintained through Week 100 in this same study [13].
The high retention rate (90%) of guselkumab-randomized patients that was observed in this trial through Week 100 further supports a durable positive risk-benefit profile. Specific to PsA-related conditions, this analysis found no exacerbations or new cases of IBD during the 2-year period of guselkumab treatment and one case of uveitis (iridocyclitis) through Week 100, with comparable incidence in the placebo group through Week 24 [13]. The absence of IBD occurrence and the very low incidence of uveitis are in line with long-term guselkumab safety data previously reported and through up to 2 years in the largest cohort of PsA patients assessed to date [33], through up to 5 years among patients with moderate-to-severe psoriasis [34, 35], and through up to 5 years among a large population of patients with psoriatic disease from 11 Phase 2/3 studies [36].

The durable effectiveness of guselkumab in such a broad range of PsA domains is likely associated with the central role of IL-23 in the pathophysiology of psoriasis and inhibition of Th17 clonal expansion through IL-23p19-subunit blockade [37]. Biomarker studies in patients with active PsA have shown that guselkumab treatment leads to reductions in circulating protein levels of acute phase and Th17 effector cytokines through Week 24 [38], as well as serum collagen levels (including C1M), through Week 52 [39]. These pharmacodynamic effects were sustained, or in some cases, enhanced through Week 100 [40] and associated with enduring clinical improvements in PsA disease activity through Week 100 [40, 41]. Preliminary in vitro studies have demonstrated that guselkumab, as a fully human IgG1 monoclonal antibody with a native Fc region, has high affinity for binding of the IL-23 p19 subunit, high potency for inhibiting IL-23 signaling, and dose-dependent Fc-mediated binding to the Fcγ receptor I found on primary human inflammatory monocytes, also known as CD64. CD64-bound guselkumab was further shown to simultaneously capture IL-23 endogenously secreted from the same cells [42]. Although the clinical implications of guselkumab Fcγ receptor binding to CD64 are not yet clear, it is possible that the durable and substantial multi-domain effectiveness of guselkumab may be related to its unique molecular attributes. Given that CD64⁺ IL-23-producing myeloid cells are increased within inflamed tissue of patients with psoriatic disease [43] and joint disease activity positively correlates with frequency of peripheral CD64⁺ monocytes [44], these findings may suggest a mechanistic benefit. Thus, the dual-acting capability of guselkumab may neutralize inflammation at its cellular source by potently block IL-23 activity and binding CD64 and may contribute to differences in therapeutic profiles across antibodies inhibiting IL-23 [45].

As with all data derived from clinical trials, findings may not be generalizable to all patients seen in routine care and incentives for investigators and patients may have influenced patient retention. Furthermore, the analysis may not have been powered to detect rare safety signals, with additional larger studies required to accurately quantify the incidence of IBD and uveitis during guselkumab treatment. However, a safety analysis involving ~4,400 patients with psoriatic disease found the rates of uveitis were similar in guselkumab- and placebo-treated patients, with no cases of Crohn's disease or ulcerative colitis reported in guselkumab-treated patients through 5 years [36]. The absence of data collection on nail psoriasis in DISCOVER-2 is an additional limitation of this study assessing key GRAPPA-identified domains. Additionally, identification of patients with axial involvement in this study was limited by the use of locally-read imaging that was restricted to evaluation of sacroiliitis and did not objectively assess spinal inflammation. The present study did not examine the influence of baseline patient characteristics on guselkumab efficacy; however, a previous analysis of a broad population of patients with active PsA in the DISCOVER-1 and 2 studies demonstrated robust and durable guselkumab efficacy across evaluated disease domains irrespective of baseline demographics, disease characteristics, and PsA medication use [46]. Specifically, higher response rates were observed with guselkumab than placebo in joint and skin disease, fatigue, functional status, and composite measures of PsA disease activity at Week 24 across patient subgroups stratified by patient sex and baseline body mass index,
swollen and tender joint counts, CRP levels, PsA duration, and use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or methotrexate. As well, response rates within each baseline subgroup were sustained or increased through 1 year [46]. Direct subgroup comparisons, including males vs. females and patients on monotherapy vs. combination therapy with methotrexate, have not been previously conducted, and are an important area of future investigation. Although the current analysis included only biologic-naïve patients with active PsA, the effectiveness of guselkumab has also been shown in tumor necrosis factor inhibitor experienced patients, including a real-world PsA population characterized by longstanding, treatment-resistant, active disease at baseline [47-49]. Furthermore, the long-term effectiveness of guselkumab in routine care is being examined in the ongoing prospective observational PsABIOnd study conducted in 20 countries worldwide [50]. Strengths of the current analyses include the conservative NRI approach that assigns non-response for all missing data and was employed at low rates (<10%) reflecting those of study discontinuation; the randomized controlled design of DISCOVER-2; and the focus on guselkumab effectiveness across important disease domains, which aligns with GRAPPA recommendations for PsA treatment and is relevant to clinical practice.

## CONCLUSION

In the DISCOVER-2 study of biologic-naïve patients with highly active PsA, both guselkumab regimens (Q4W and Q8W) provided early, durable, and continuous improvements in key GRAPPA-recommended domains of PsA through up to 2 years of treatment, resulting in considerable proportions achieving low levels of joint disease activity, enthesitis/dactylitis resolution, complete skin clearance, and low/minimal levels of overall disease activity. No exacerbations or new onset of IBD were reported, with a single occurrence of uveitis observed through Week 100 in guselkumab-treated patients, aligning with the established safety profile of guselkumab.
391 Acknowledgements

392 The authors wish to acknowledge Christine Contré (formerly of Janssen Pharmaceutical Companies of
393 Johnson and Johnson) for contribution in the design of the analysis as well as Fiona Allum and Joanna
394 Dembowy of JSS Medical Research for medical writing and editorial assistance during the preparation of
395 this manuscript.

396

397 Competing Interests

398 LCC: received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer
399 and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead,
400 Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB; and has been paid as a speaker for AbbVie,
401 Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medac, Novartis, Pfizer,
402 and UCB. Dr. Coates is supported by the National Institute for Health Research (NIHR) Oxford Biomedical
403 Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the
404 NHS, the NIHR, or the Department of Health. Dr. Coates is an associate editor at RMD Open.

405 LG: received research grants from AbbVie, Biogen, Eli Lilly, Novartis, UCB; consulting fees from AbbVie,
406 Amgen, BMS, Celltrion, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB.

407 MZ: employee of Janssen EMEA Medical Affairs Immunology, LLC, Zug, Switzerland; owns stock or stock
408 options in Johnson & Johnson.

409 MS: employee of Janssen Research & Development, LLC; owns stock or stock options in Johnson &
410 Johnson.

411 ER: employee of JSS Medical Research; paid consultant of Janssen.

412 NJS: employee of Janssen Scientific Affairs, LLC, a subsidiary of Johnson & Johnson; received salary
413 support from the Childhood Arthritis and Rheumatology Research Alliance within the past 3 years; owns
414 or has owned stock in AbbVie, Gilead, Iovance, Johnson & Johnson, Novo-Nordisk, and Pfizer within the
415 past 3 years. Current stock ownership: AbbVie, Gilead, Iovance, Jazz, Johnson & Johnson, Novavax, and
416 Viatris.

417 APK: employee of Janssen Research & Development, LLC, a wholly owned subsidiary of Johnson &
418 Johnson, and own stocks in Johnson & Johnson.

419 XLX: employee of Janssen Research & Development, LLC, a wholly owned subsidiary of Johnson &
420 Johnson; owns stock in Johnson & Johnson.

421 PN: received funding for research and clinical trials and honoraria for advice and lectures on behalf of
422 Abbvie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos,
423 GlaxoSmithKline, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Dr. Nash is an editorial board member
424 at RMD Open.

425 PJM: received research grants from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen,
426 Novartis, Pfizer, SUN Pharma, and UCB; consulting fees from AbbVie, Acelyrin, Aclaris, Amgen,
427 Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Immagene,
428 Janssen, Novartis, Pfizer, SUN, UCB, Ventyx; and speaker fees from AbbVie, Amgen, Eli Lilly, Janssen,
429 Novartis, Pfizer, and UCB.

430 PSH: received consulting fees from Eli Lilly and fees for educational services from AbbVie, Amgen,
431 Janssen, and Novartis.

432
433 Funding

434 This study was supported by Janssen Research & Development, LLC, Spring House, PA/San Diego, CA,

435 USA.

436

437 Data Availability Statement

438 The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is

439 available at https://www.janssen.com/clinical-trials/transparency. As noted on this site,

440 requests for access to the study data can be submitted through Yale Open Data Access

441 (YODA) Project site at http://yoda.yale.edu.
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<table><caption>Table 1 Baseline patient and disease characteristics.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Guselkumab 100 mg</th></tr><tr><th>Q4W (N=245)</th><th>Q8W (N=248)</th></tr></thead><tbody><tr><td><strong>Demographics</strong></td><td></td><td></td></tr><tr><td>Age, years</td><td>45.9 (11.5)</td><td>44.9 (11.9)</td></tr><tr><td>Male</td><td>142 (58%)</td><td>129 (52%)</td></tr><tr><td>Body weight, kg</td><td>85.8 (19.5)</td><td>83.0 (19.3)</td></tr><tr><td><strong>PsA Characteristics</strong></td><td></td><td></td></tr><tr><td>PsA disease duration, years</td><td>5.5 (5.9)</td><td>5.1 (5.5)</td></tr><tr><td>CRP, mg/dL</td><td>1.2 (0.6-2.3)</td><td>1.3 (0.7-2.5)</td></tr><tr><td>SJC (0-66)</td><td>12.9 (7.8)</td><td>11.7 (6.8)</td></tr><tr><td>TJC (0-68)</td><td>22.4 (13.5)</td><td>19.8 (11.9)</td></tr><tr><td>Patients with axial symptoms<sup>a</sup></td><td>82 (33%)</td><td>68 (27%)</td></tr><tr><td>Spinal pain (0-10)<sup>b</sup></td><td>6.5 (2.2)</td><td>6.6 (2.2)</td></tr><tr><td>Patients with enthesitis</td><td>170 (69%)</td><td>158 (64%)</td></tr><tr><td>LEI (0-6)<sup>c</sup></td><td>3.0 (1.7)</td><td>2.6 (1.5)</td></tr><tr><td>Patients with dactylitis</td><td>121 (49%)</td><td>111 (45%)</td></tr><tr><td>DSS (0-60)<sup>d</sup></td><td>8.6 (9.6)</td><td>8.0 (9.6)</td></tr><tr><td>BSA, %</td><td>18.2 (20.0)</td><td>17.0 (21.0)</td></tr><tr><td>Skin VAS (0-100 mm)</td><td>60.9 (22.6)</td><td>59.2 (25.3)</td></tr><tr><td>PASI (0-72)</td><td>10.8 (11.7)</td><td>9.7 (11.7)</td></tr><tr><td>Patients with BSA ≥3% and IGA score ≥2</td><td>184 (75.1%)</td><td>176 (71.0%)</td></tr><tr><td>Skin VAS (0-100 mm)<sup>e</sup></td><td>64.4 (20.3)</td><td>65.3 (21.9)</td></tr><tr><td>PASI (0-72)<sup>e</sup></td><td>13.8 (12.0)</td><td>12.9 (12.5)</td></tr><tr><td>DAPSA<sup>f</sup></td><td>49.7 (21.1)</td><td>46.3 (19.4)</td></tr><tr><td>cDAPSA<sup>g</sup></td><td>47.9 (20.9)</td><td>44.3 (18.8)</td></tr><tr><td>PASDAS<sup>h</sup></td><td>6.6 (1.09)</td><td>6.6 (1.09)</td></tr><tr><td>HAQ-DI (0-3)</td><td>1.2 (0.6)</td><td>1.3 (0.6)</td></tr><tr><td><strong>Concomitant medications</strong></td><td></td><td></td></tr><tr><td>Methotrexate</td><td>146 (60%)</td><td>141 (57%)</td></tr><tr><td>Oral corticosteroids</td><td>46 (19%)</td><td>50 (20%)</td></tr></tbody></table>

Data are n (%), mean (SD), or median (IQR). <sup>a</sup>Patients were identified by the investigator as having axial symptoms and had imaging-confirmed sacroiliitis. <sup>b</sup>Among patients with axial symptoms and available spinal pain score at baseline (Q4W group n=79 and Q8W n=62). <sup>c</sup>Among patients with enthesitis and available LEI score at baseline (Q4W group n=166 and Q8W n=157). <sup>d</sup>Among patients with dactylitis and available DSS at baseline (Q4W group n=121 and Q8W n=111). <sup>e</sup>Among patients with BSA ≥3% & IGA score ≥2 at baseline (Q4W group n=184 and Q8W n=176). <sup>f</sup>DAPSA disease activity states include remission (≤4), low disease activity (>4 and ≤14), moderate disease activity (>14 and ≤28), and high
disease activity (>28) [21]. ⁹cDAPSA disease activity states include remission (≤4), low disease activity (>4 and ≤13), moderate disease activity (>14 and ≤27), moderate (score >3.2 to <5.4), and high disease activity (>27) [21]. ⁷PASDAS disease activity states include very low (≤1.9), low (>1.9 to ≤ 3.2), and high disease activity (≥5.4) [17, 22].

BSA=body surface area; CRP=C-reactive protein; cDAPSA=clinical Disease Activity Index for Psoriatic Arthritis; DAPSA=Disease Activity Index for Psoriatic Arthritis; DSS=dactylitis severity score; HAQ-DI=health assessment questionnaire-disability index; IGA=Investigator's Global Assessment of psoriasis; IQR=interquartile range; LEI=Leeds enthesitis index; PASDAS=Psoriatic Arthritis Disease Activity Score (0-10); PASI=Psoriasis Area and Severity Index; PsA=psoriatic arthritis; Q4W=every 4 weeks; Q8W=every 8 weeks; SD=standard deviation; SJC=swollen joint count (0-66); TJC=tender joint count (0-68); VAS=Visual Analog Scale
<figure><img src="image_2.png" /></figure>

605 All changes from baseline were significant at the 0.05 level. x=PASI not assessed at Week 8. N represents
606 patients with available score at baseline. DSS=Dactylitis Severity Score; GUS=guselkumab; LEI=Leeds
607 Enthesitis Index; LS Mean=least squares mean; PASI=Psoriasis Area and Severity Index; PsA=psoriatic
608 arthritis; Q4W= every 4 weeks; Q8W=every 8 weeks; SJC=swollen joint count; TJC=tender joint count;
609 VAS=Visual Analog Scale; LEI was analyzed among patients with enthesitis and available LEI score at
610 baseline. DSS was analyzed among patients with dactylitis and available DSS at baseline. Skin VAS and
611 PASI were analyzed among patients with body surface area ≥3% and Investigator's Global Assessment of
612
613 psoriasis score ≥2 at baseline. Spinal pain was analyzed among patients with axial symptoms and

614 imaging-confirmed sacroiliitis.
<table><caption>615 Table 2 Achievement of therapeutic targets among guselkumab-randomized patients over time (NRI)</caption><thead><tr><th rowspan="2">Week</th><th colspan="5">Guselkumab 100mg Q4W</th><th colspan="5">Guselkumab 100mg Q8W</th></tr><tr><th>8</th><th>16</th><th>24</th><th>52</th><th>100</th><th>8</th><th>16</th><th>24</th><th>52</th><th>100</th></tr></thead><tbody><tr><td><strong>DAPSA</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LDA (≤14)</td><td>43 (18)</td><td>61 (25)</td><td>88 (36)</td><td>125 (51)</td><td>151 (62)</td><td>43 (17)</td><td>79 (32)</td><td>97 (39)</td><td>130 (52)</td><td>147 (59)</td></tr><tr><td>Remission (≤4)</td><td>5 (2)</td><td>12 (5)</td><td>21 (9)</td><td>39 (16)</td><td>52 (21)</td><td>3 (1)</td><td>15 (6)</td><td>23 (9)</td><td>46 (19)</td><td>60 (24)</td></tr><tr><td><strong>cDAPSA</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LDA (≤13)<sup>a</sup></td><td>41 (17)</td><td>58 (24)</td><td>89 (36)</td><td>125 (51)</td><td>150 (61)</td><td>44 (18)</td><td>75 (30)</td><td>95 (38)</td><td>131 (53)</td><td>147 (60)</td></tr><tr><td>Remission (≤4)</td><td>5 (2)</td><td>13 (5)</td><td>29 (12)</td><td>44 (18)</td><td>59 (24)</td><td>4 (2)</td><td>19 (8)</td><td>25 (10)</td><td>53 (21)</td><td>65 (26)</td></tr><tr><td><strong>Enthesitis resolution<sup>b</sup></strong></td><td>45 (27)</td><td>66 (40)</td><td>71 (43)</td><td>93 (56)</td><td>102 (61)</td><td>50 (32)</td><td>75 (48)</td><td>87 (55)</td><td>97 (62)</td><td>110 (70)</td></tr><tr><td><strong>Dactylitis resolution<sup>b</sup></strong></td><td>39 (32)</td><td>64 (53)</td><td>80 (66)</td><td>90 (74)</td><td>87 (72)</td><td>34 (31)</td><td>51 (46)</td><td>66 (59)</td><td>86 (77)</td><td>92 (83)</td></tr><tr><td><strong>Skin</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>PASI90<sup>c,d</sup></td><td>-</td><td>100 (54)</td><td>114 (62)</td><td>142 (77)</td><td>136 (74)</td><td>-</td><td>97 (55)</td><td>121 (69)</td><td>131 (74)</td><td>123 (70)</td></tr><tr><td>PASI100<sup>c,d</sup></td><td>-</td><td>62 (34)</td><td>83 (45)</td><td>106 (58)</td><td>109 (59)</td><td>-</td><td>48 (27)</td><td>80 (45)</td><td>93 (53)</td><td>94 (53)</td></tr><tr><td>IGA 0/1 response<sup>c-e</sup></td><td>-</td><td>122 (66)</td><td>127 (69)</td><td>147 (80)</td><td>140 (76)</td><td>-</td><td>110 (62)</td><td>124 (70)</td><td>131 (74)</td><td>126 (72)</td></tr><tr><td>Skin VAS ≤15mm<sup>d,f</sup></td><td>26 (14)</td><td>58 (32)</td><td>68 (37)</td><td>93 (51)</td><td>96 (53)</td><td>38 (22)</td><td>61 (36)</td><td>71 (42)</td><td>88 (52)</td><td>95 (56)</td></tr><tr><td><strong>PASDAS</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LDA (≤3.2)</td><td>25 (10)</td><td>44 (18)</td><td>58 (24)</td><td>105 (43)</td><td>126 (51)</td><td>28 (11)</td><td>56 (23)</td><td>76 (31)</td><td>106 (43)</td><td>122 (49)</td></tr><tr><td>Remission (≤1.9)</td><td>4 (2)</td><td>11 (4)</td><td>22 (9)</td><td>36 (15)</td><td>51 (21)</td><td>2 (1)</td><td>16 (6)</td><td>23 (9)</td><td>52 (21)</td><td>58 (23)</td></tr><tr><td><strong>MDA<sup>a</sup></strong></td><td>8 (3)</td><td>33 (14)</td><td>47 (19)</td><td>83 (34)</td><td>93 (38)</td><td>9 (4)</td><td>42 (17)</td><td>63 (25)</td><td>77 (31)</td><td>100 (40)</td></tr></tbody><tfoot><tr><td colspan="11" style="text-align: center;"><strong>Absolute change in response rate from previous visit</strong></td></tr><tr><td></td><td colspan="2" style="text-align: center;">± 1 to &lt;5</td><td colspan="2" style="text-align: center;">+ 5 to &lt;10</td><td colspan="2" style="text-align: center;">+ 10 to &lt;15</td><td colspan="2" style="text-align: center;">+ 15 to &lt;20</td><td colspan="2" style="text-align: center;">≥20</td></tr></tfoot></table>

616 Number (%) of guselkumab-randomized patients (N=493) achieving therapeutic endpoints over time (NRI) are shown. <sup>a</sup>Excludes patients who achieved endpoint at baseline. <sup>b</sup>Among patients with domain at baseline. <sup>c</sup>PASI and IGA not assessed at Week 8. <sup>d</sup>Among patients with baseline IGA ≥2 and BSA ≥3%. <sup>e</sup>IGA skin response=score of 0 or 1 and ≥2 grade improvement from baseline. <sup>f</sup>Patients with Skin VAS >15mm at baseline.

617 BSA=body surface area; cDAPSA=clinical Disease Activity Index for Psoriatic Arthritis; DAPSA=Disease Activity Index for Psoriatic Arthritis; 618 IGA=Investigator's Global Assessment of psoriasis; LDA=Low Disease Activity; MDA=Minimal Disease Activity; NRI=nonresponder imputation; 620
621 PASDAS=Psoriatic Arthritis Disease Activity Score; PASI90/100= ≥90% improvement/100% improvement Psoriasis Area and Severity Index;

622 Q4W=every 4 weeks; Q8W=every 8 weeks; VAS=Visual Analog Scale.
<figure><img src="image_3.png" /></figure>

Outer circles indicate greater improvement in outcome measures. Results are shown in logarithmic scale due to scale difference in the outcomes assessed. DSS=Dactylitis Severity Score; LEI=Leeds Enthesitis Index; PsA=psoriatic arthritis; Q4W=every 4 weeks; Q8W=every 8 weeks; SJC=swollen joint count; TJC=tender joint count; VAS=Visual Analog Scale; W=week.