# Efficacy of Risankizumab Across GRAPPA Domains in Psoriatic Arthritis: A Pooled Analysis of Patients From the Phase 3 KEEPsAKE 1 and 2 Studies

Laura Coates, Ricardo Blanco, Frank Behrens, Alexis Ogdie, Filip van den Bosch, Roberto Ranza, Yael Klionsky, Ahmed Soliman, Michael Chen, Derek Coombs, et al.

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Laura Coates, Ricardo Blanco, Frank Behrens, Alexis Ogdie, Filip van den Bosch, et al. Efficacy of Risankizumab Across GRAPPA Domains in Psoriatic Arthritis: A Pooled Analysis of Patients From the Phase 3 KEEPsAKE 1 and 2 Studies. RMD Open, 2025, 11 (3), pp.e005522. 10.1136/rmdopen-2025-005522. [hal-05441228](https://hal.science/hal-05441228v1)

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# Efficacy of Risankizumab Across GRAPPA Domains in Psoriatic Arthritis: A Pooled Analysis of Patients From the Phase 3 KEEPsAKE 1 and 2 Studies

Laura C. Coates,<fnref n="1" /> Ricardo Blanco,<fnref n="2" /> Frank Behrens,³ Alexis Ogdie,<fnref n="4" /> Filip Van den Bosch,<fnref n="5" />

Roberto Ranza,⁶ Yael Klionsky,<fnref n="7" /> Ahmed M. Soliman,<fnref n="8" /> Michael Chen,<fnref n="8" /> Derek Coombs,<fnref n="8" /> Linyu

Shi,<fnref n="8" /> Jamie R. Urbanik,<fnref n="8" /> Thomas Iyile,<fnref n="8" /> Ralph Lippe,<fnref n="8" /> Laure Gossec<fnref n="9" />,¹⁰

## Corresponding Author

Laura C. Coates, MBChB, PhD

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

E-mail address: laura.coates@ndorms.ox.ac.uk

## ABSTRACT

**Objective:** To assess the efficacy of long-term treatment with risankizumab across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) domains and key related conditions of psoriatic arthritis (PsA).

**Methods:** This post hoc analysis primarily used data from the phase 3 KEEPsAKE 1 trial of adult patients with PsA, with data from KEEPsAKE 2 pooled for pre-specified outcomes. Outcomes measuring risankizumab efficacy across key GRAPPA-recognized domains of PsA (peripheral arthritis, enthesitis, dactylitis, skin and nail psoriasis, axial disease) and PsA-related conditions such as inflammatory bowel disease (IBD) and uveitis were assessed over 100 weeks of treatment (~ 2 years). Statistical approaches included non-responder imputation (as-observed with imputation) for categorical variables and mixed-effect model for repeated measures for continuous variables including as-observed measurements at all visits. PsA-related conditions were evaluated via adverse events through 100 weeks.

**Results:** Overall, in KEEPsAKE 1 and KEEPsAKE 2, 412/483 (85.3%) and 181/224 (80.8%) of patients randomized to risankizumab completed treatment to week 100. Risankizumab demonstrated efficacy across all GRAPPA-defined domains through 100 weeks, including swollen and tender joint counts, enthesitis, dactylitis, skin and nail outcomes, and axial disease. In KEEPsAKE 1, 42.4% of patients had achieved a Disease Activity in Psoriatic Arthritis measurement of low disease activity and 62.9% had reached a minimal clinically important difference in pain at week 100. Rates of new onset or flare of IBD and uveitis were low.

<footnote n="1">¹Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK;</footnote>

<footnote n="2">²Hospital Universitario Marqués de Valdecilla, Immunopathology Group, IDIVAL, Santander, Spain; ³Rheumatology, Immunology, Inflammation Medicine University Hospital & Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Fraunhofer Cluster of Excellence for Immune-Mediated Disease (CIMD), Goethe University, Frankfurt, Germany;</footnote>

<footnote n="4">⁴Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA;</footnote>

<footnote n="5">⁵Department of Rheumatology, Ghent University, VIB Center for Inflammation Research, Ghent, Belgium; ⁶Rheumatology Unit, Hospital das Clínicas, Federal University of Uberlândia, Uberlândia, Brazil;</footnote>

<footnote n="7">⁷Wake Forest University School of Medicine, Winston-Salem, NC, USA;</footnote>

<footnote n="8">⁸AbbVie Inc., North Chicago, IL, USA;</footnote>

<footnote n="9">⁹INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France; ¹⁰Rheumatology Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France</footnote>
**Conclusions:** Treatment with risankizumab provides durable improvement in the signs and symptoms of PsA across all GRAPPA disease domains and related conditions.

**Keywords:** psoriatic arthritis, biological therapy, DMARD

## WHAT IS ALREADY KNOWN ON THIS TOPIC

* The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommends that the goal of therapy for patients with psoriatic arthritis (PsA) is to achieve the lowest possible level of disease activity in all 6 domains of disease, including consideration of related conditions of inflammatory bowel disease (IBD) and uveitis.

* For patients with active PsA with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR) and/or biologic DMARDs (bDMARD-IR), risankizumab, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits Interleukin 23 (IL-23) by binding to its p19 subunit, has been shown to be generally well tolerated and have significant efficacy at week 24, with a consistent long-term safety and efficacy profile over 148 weeks of treatment.

## WHAT THIS STUDY ADDS

* Risankizumab treatment with dose intervals of 12 weeks, after two initiation doses, provides improvements in all assessed GRAPPA-recognized PsA domains through 100 weeks (2 years) of treatment, with a high proportion of patients achieving low/minimal levels of overall disease activity, low levels of joint disease activity, resolution of enthesitis/dactylitis, and clearance of skin and nail psoriasis.

* Events of IBD and uveitis were rare, with 4 new onset cases reported with risankizumab for each (<0.1 E/100 patient years [PY]) and 3 flares for each (<0.1 E/100 PY).

## HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY

* This study demonstrates durable efficacy of treatment with risankizumab across all 6 GRAPPA domains of PsA and key related conditions, poising it as an effective treatment option that addresses the therapeutic domains recognized by GRAPPA for patients with PsA.

## INTRODUCTION

Psoriatic arthritis (PsA) is a heterogenous rheumatologic disease with key musculoskeletal (MSK) manifestations in peripheral joints (joint tenderness and swelling, enthesitis, dactylitis), the spine, as well as skin.<sup>1-4</sup> The clinical burden of PsA includes progressive joint damage, dactylitis, enthesitis, cutaneous manifestations, comorbidities, and the presence of extra-musculoskeletal manifestations (EMMs; including inflammatory bowel disease [IBD] and uveitis); chronic pain, impaired function, and progressive disability can affect the overall burden of disease and patient quality of life (QoL).<sup>2, 5-8</sup>

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), founded in 2003,<sup>9</sup> aims to develop and periodically update recommendations for the optimal treatment and management of patients with PsA, based upon evolving scientific evidence. The most recent recommendations, updated in 2021,<sup>3</sup> consider the advances in therapeutic options for PsA since GRAPPA's previous recommendations in 2015.<sup>10</sup> The updated GRAPPA recommendations consider the key domains of PsA which impact patients' quality of life and prognosis: peripheral arthritis, axial disease, enthesitis, dactylitis, skin and nail psoriasis, PsA-related conditions such as IBD and uveitis, and associated comorbidities.<sup>3, 11,12</sup>
Interleukin-23 (IL-23) is a key regulatory cytokine that is essential for the activation of pathogenic T helper 17 (Th17) cells that stimulate inflammation in both psoriasis and PsA.¹³ Risankizumab inhibits IL-23 by targeting the p19 subunit with high affinity and specificity, inhibiting the activation of the pathogenic Th17 cells.¹³ Risankizumab is approved for the treatment of moderate to severe psoriasis, active PsA, moderately to severely active Crohn's disease (CD), and moderately to severe ulcerative colitis (UC) in adults.¹⁴ The KEEPSAKE 1 and KEEPSAKE 2 clinical trials have demonstrated that treatment with risankizumab delivers durable efficacy across multiple PsA domains up to week 100, and is associated with improved QoL, patient functioning, pain, and nail involvement.¹⁵⁻²²

This post hoc analysis aimed to assess the efficacy of long-term treatment with
risankizumab across the updated GRAPPA domains and key related conditions of PsA.

METHODS

Patients

This post hoc analysis included patients with active PsA who are participants in 2 ongoing, multicenter, double-blind, phase 3 trials – KEEPSAKE 1 (N = 964; NCT03675308) and KEEPSAKE 2 (N = 443; NCT03671148).¹⁵, ¹⁶, ²⁰, ²¹

Study Design and Treatment

The study design, patient eligibility criteria, and initial patient population have been previously reported in detail for KEEPSAKE 1 and KEEPSAKE 2.¹⁵, ¹⁶, ²⁰, ²¹ Both double-blind phase 3 studies enrolled adult PsA patients with an inadequate response, intolerance, or contraindication to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1 or 2 biologic DMARDs (bDMARD-IR; KEEPSAKE 2 only). Period 1 of each study consisted of a 24-week double-blind, placebo controlled, parallel-group treatment. Patients were randomized 1:1 to receive subcutaneous administration of risankizumab 150 mg or placebo at weeks 0, 4 and 16. Period 2 started at week 24, and to maintain blinding of treatment in period 1, patients who were randomized to risankizumab received blinded placebo at week 24, and patients who were randomized to placebo received the first dose of blinded risankizumab at week 24. Starting at week 28, all patients received open-label risankizumab 150 mg every 12 weeks. KEEPSAKE 1 and KEEPSAKE 2 were conducted in accordance with the International Conference for Harmonisation guidelines, applicable regulations, and the Declaration of Helsinki. The Independent Ethics Committee or Institutional Review Board at each study site approved the study protocol, the informed consent forms, and the recruitment materials before patient enrollment. All patients provided written informed consent at screening.

Outcomes
The impact of risankizumab across GRAPPA domains was evaluated across 2 years (at week 24, week 52, and week 100) using multiple outcome measures for resolution and improvement of disease activity, as outlined in Table 1.

## Peripheral Arthritis

Efficacy for peripheral arthritis was assessed using achievement of ≥ 20%, 50%, or 70% improvement in PsA signs and symptoms using American College of Rheumatology criteria (ACR20), ACR50, and ACR70 over time; maintenance of ACR20, ACR50 and ACR70 responses over time; improvement in swollen joint count in 66 joints (SJC66) and tender joint count in 68 joints (TJC68); maintenance of resolution in SJC66 and TJC68 over time; assessment of disease activity based on Disease Activity in Psoriatic Arthritis (DAPSA) scores with cut-offs as follows: remission ≤ 4, low disease activity (LDA) > 4 - ≤ 14, moderate disease activity (MDA) > 14 - ≤ 28, and high disease activity > 28; achievement of minimal clinically important difference (MCID) in pain, assessed as a ≥ 10-point decrease in patient's assessment of pain,²³ for patients with patient's assessment of pain ≥ 10 at baseline; assessment of patients with no radiographic progression in KEEPSAKE 1 (change from baseline in PsA-modified Total Sharp Score (mTSS) ≤ 0 and PsA-mTSS ≤ 0.5).

## Enthesitis and Dactylitis

Efficacy for enthesitis and dactylitis was assessed by achievement of Leeds Enthesitis Index²⁴ (LEI) = 0, among patients with LEI > 0 at baseline, achievement of Leeds Dactylitis Index²⁵ (LDI) = 0, among patients with LDI > 0 at baseline, and maintenance of resolution of enthesitis and dactylitis.

## Psoriasis

Among patients with body surface area of psoriasis (BSA) ≥ 3% at baseline, efficacy for skin disease activity was assessed using ≥ 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90), maintenance of PASI90 over time, complete resolution (PASI100), and achievement of absolute PASI ≤ 1.

### Nail Psoriasis

Efficacy in nail psoriasis was assessed only in the KEEPSAKE 1 study through mean change from baseline and achievement of improvement in the modified Nail Psoriasis Severity Index (mNAPSI)²⁶, the Physician's Global Assessment of Fingernail Psoriasis (PGA-F)²⁷ scores, and achievement of “clear” or “minimal” nail psoriasis (PGA-F = 0 or 1 with ≥ 2-grade improvement from baseline). The mNAPSI tool used to assess the severity of nail psoriasis, produces a score range of 0 to 13 for each individual fingernail and a cumulative score range of 0 to 130 across all ten fingernails, where higher scores denote more severe nail involvement.²⁶ The PGA-F tool was used to assess the severity of fingernail psoriasis. It categorizes the severity into five categories - clear (0), minimal (1), mild (2), moderate (3), and severe (4), with higher scores indicating more severe disease.²⁸

### Axial Disease

In patients with psoriatic spondylitis at baseline, based upon investigator clinical assessment (including patients with spondylitis), efficacy of risankizumab for axial disease was assessed by achievement of MCID in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and modified BASDAI (excluding Question 3 for peripheral arthritis), defined as ≥ 1.1-point decrease, for patients with BASDAI/modified BASDAI ≥ 1.1 at baseline; achievement of ≥ 2-point decrease from baseline in modified BASDAI among patients with baseline mBASDAI ≥ 2 and achievement of ≥ 1.1-point decrease from baseline in ASDAS among patients with baseline
ASDAS ≥ 1.1 to show clinically important improvement (CII) based on the ASAS-EULAR guidelines;²⁹ maintenance of MCID in BASDAI and modified BASDAI for KEEPsAKE 1; mean change from baseline in BASDAI and modified BASDAI; mean change from baseline in BASDAI spinal pain (Question 2), and mean change from baseline in the Ankylosing Spondylitis Disease Activity Score (ASDAS).³⁰

## EMMs – IBD and Uveitis

To assess the development of key related conditions, as identified in the GRAPPA domains, among patients with PsA treated with risankizumab treatment-emergent adverse events (TEAEs) of EMMs, including IBD and uveitis were analyzed. TEAEs were defined as an AE with onset on or after first dose of study drug and ≤ 140 days after last dose and were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 26.1. Associated preferred terms of investigator-reported TEAEs were manually grouped into categories representing IBD (inclusive of “inflammatory bowel disease,” “colitis ulcerative,” “colitis,” “Crohn’s disease,” and “proctitis”) and uveitis (inclusive of “uveitis,” “iridocyclitis,” and “iritis”). The occurrence of EMMs was reported as exposure-adjusted event rates (EAERs), expressed as the number of events per 100 patient years (E/100 PY), and were reported separately based on whether patients had a reported history (thus experiencing a flare) of the respective EMM or experienced a new onset event.

## Statistical Analysis

The efficacy analyses for outcomes assessed for peripheral arthritis (ACR20/50/70, DAPSA, pain, SJC and TJC, and radiographic progression), skin psoriasis (PASI90/100 and PASI ≤ 1), and nail psoriasis (mNAPSI and PGA-F 0/1) utilized data from patients participating in the KEEPsAKE 1 study (csDMARD-IR patients). For outcomes assessed for axial manifestations, enthesitis, and dactylitis, which are based on subgroups of patients with these manifestations at baseline, efficacy analyses utilized pooled data from patients participating in the KEEPsAKE 1 and KEEPsAKE 2 studies. Categorical endpoints were reported by multiple imputation methods; data through week 24 were reported using non-responder imputation (NRI) with missing data due to COVID-19 handled by multiple imputation (NRI-C); long-term analysis (weeks 24 - 100) used NRI with multiple imputation (NRI-MI) for missing data due to COVID-19 for categorical variables based on as-observed (AO) data, and to handle missing data due to geopolitical conflict in Ukraine and Russia (applicable for KEEPsAKE 1 only); all other missing data were treated as non-responders. Continuous efficacy endpoints were analyzed using a mixed-effect model for repeated measures (MMRM), at all the time points. Distribution of DAPSA disease activity level and percentage of patients with no radiographic progression was reported using the AO approach.

## RESULTS

### Patients

For analyses based on the KEEPsAKE 1 study, 964 randomized patients were included, with 939 (97.4%) eligible patients entering period 2 to receive open-label risankizumab. For analyses including the pooled KEEPsAKE 1 and KEEPsAKE 2 population, 1407 patients, pooled from 2 studies, were included. Of these, 700 patients received placebo and 707 patients received continuous risankizumab 150 mg. As previously reported, demographics and baseline characteristics were generally balanced between the cohorts. In the continuous risankizumab cohort, female patients comprised 47.8% in the KEEPsAKE 1 trial and 55.4% in the KEEPsAKE 2 trial, and ranged in age from 20 to 85 years across both trials.¹⁶, ²⁰

### Efficacy
## Peripheral Arthritis

As previously reported, significantly more patients receiving risankizumab in the KEEPsAKE 1 study achieved the primary endpoint of ACR20 at week 24 (57.3% compared with 33.5% in the placebo group).16, 20 At week 100, 64.3% of patients in the continuous risankizumab cohort met ACR20 criteria, consistent with the 70.6% response rate observed at week 52. Among patients receiving continuous risankizumab who achieved an ACR20 response at week 24, 89.1% and 80.3% maintained the response to week 52 and week 100, respectively; 81.2% of patients who achieved ACR20 at week 52 maintained the response at week 100 (Supplemental Figure 1). For ACR50 and ACR70, 72.4% and 63.5% of patients receiving continuous risankizumab who achieved these outcomes at week 24 maintained their response at week 100.31, 32

Among patients in the continuous risankizumab cohort, 12.2%, 23.4%, and 25.9% achieved DAPSA remission, and 43.5%, 65.7%, and 68.3% achieved DAPSA LDA/remission at week 24, 52, and 100 in KEEPsAKE 1, respectively (Figure 1). An MCID in patient's assessment of pain was achieved by 63.4%, 67.0%, and 62.9% of patients receiving continuous risankizumab in KEEPsAKE 1 at week 24, 52, and 100, respectively (Figure 2A). There was no structural progression (defined as change from baseline in mTSS ≤ 0) observed at week 100 in 90.6% of patients in the continuous risankizumab cohort in KEEPsAKE 1 (Figure 2B). Patients in the continuous risankizumab cohort demonstrated improvement in SJC66 and TJC68 over 100 weeks in KEEPsAKE 1 (Figure 2C). 81.1% of patients who achieved TJC68 ≤ 1 at week 24 maintained the response at week 52 and 70.8% of patients with TJC68 ≤ 1 at week 52 maintained the response at week 100 (Supplemental Figure 2).

## Enthesitis and Dactylitis

Among patients with LEI > 0 at baseline (N = 444), 50.0%, 55.0%, and 57.7% of patients in the combined continuous risankizumab cohort from KEEPsAKE 1 and KEEPsAKE 2 achieved resolution of enthesitis at week 24, 52, and 100, respectively (Figure 3A). Among patients with LDI > 0 at baseline (N = 188), 71.3%, 76.6%, and 76.2% of patients in the combined continuous risankizumab cohort achieved resolution of dactylitis at week 24, 52, and 100, respectively (Figure 3B). Among patients who achieved resolution of enthesitis at week 24, 80.6% maintained the response at week 52; 79.7% of week 52 responders maintained the response at week 100 (Supplemental Figure 3). Among patients who achieved resolution of dactylitis at week 24, 89.1% maintained the response at week 52; 89.3% of week 52 responders maintained the response at week 100 (Supplemental Figure 3).

## Psoriasis

As reported previously, among patients with BSA ≥ 3% at baseline (N = 273) in the KEEPsAKE 1 trial, 52.3%, 67.9%, and 71.3% in the continuous risankizumab cohort achieved PASI90 at week 24, 52, and 100, respectively.31 Similar trends were observed for PASI100 and absolute PASI ≤1, which were achieved by 33.7%, 50.2%, 52.0% and 57.7%, 69.8%, 72.7% of patients in the continuous risankizumab cohort in KEEPsAKE 1 at week 24, 52, and 100, respectively (Figure 4). Among patients who achieved PASI90 at week 24, 86.4% maintained the response at week 52; 87.7% of week 52 responders maintained the response at week 100 (Supplemental Figure 4).

## Nail Psoriasis

Patients with nail psoriasis at baseline in the continuous risankizumab cohort in KEEPsAKE 1 experienced improvement in mNAPSI scores through 100 weeks of treatment (Figure 5A). A similar trend was observed for improvement in PGA-F scores (Supplemental Figure 5). Among patients in the continuous risankizumab cohort, 38.3%, 55.9%, and 61.6% of patients in
KEEPsAKE 1 achieved a PGA-F score of “clear” or “minimal” with a ≥ 2-grade improvement at weeks 24, 52, and 100, respectively (Figure 5B).

## Axial Disease

At baseline, psoriatic spondylitis, or axial involvement, was reported in 19.6% (7.9% diagnosed by radiograph or MRI) of patients in KEEPsAKE 1 and 19.6% (5% diagnosed by radiograph or MRI) of patients in KEEPsAKE 2. Among patients with axial involvement at baseline, 51.5%, 62.0%, and 58.0% of patients receiving continuous risankizumab in the pooled patient population (KEEPsAKE 1 and KEEPsAKE 2) achieved MCID in overall BASDAI at weeks 24, 52, and 100, respectively (Figure 6A), and 54.2%, 62.7%, and 57.7% achieved MCID in modified BASDAI at weeks 24, 52, and 100, respectively (Supplemental Figure 7). Patients in the continuous risankizumab cohort demonstrated improvement in BASDAI, BASDAI spinal pain (Question 2), and ASDAS scores over 100 weeks (Figure 6 B, C, and D), as well as in modified BASDAI (Supplemental Figure 9). 45.9% of patients achieved CII in modified BASDAI and 38.2% achieved CII in ASDAS scores (Supplemental Figure 6). Among patients who achieved MCID in BASDAI at week 24, 87.7% maintained the response at week 52, and 81.3% of week 52 responders maintained the response at week 100 (Supplemental Figure 8). Among patients from KEEPsAKE 1 who achieved MCID in modified BASDAI at week 24, 88.9% maintained the response at week 52, and 76.9% maintained the response at week 100. Among patients who achieved MCID in modified BASDAI at week 52, 73.3% maintained the response at week 100 (Supplemental Figure 8).

## EMMs – IBD and Uveitis

The majority (over 99%) of patients did not have a prior history of EMMs at baseline (Figure 7). Events of IBD and uveitis were rare. There were 4 new onset cases reported with risankizumab for each (<0.1 E/100 PY) and 3 flares for each (<0.1 E/100 PY) (Figure 7).

Overall, across all domains assessed, outcomes observed in patients who were initially randomized to placebo and switched to treatment with risankizumab after week 24 were generally similar by week 100 to those initially randomized to risankizumab.

## DISCUSSION

This post hoc analysis evaluated data from 2 ongoing, multicenter, double-blind, phase 3 studies of risankizumab for PsA treatment – KEEPsAKE 1 (N = 964) and KEEPsAKE 2 (N = 443).<sup>15, 16, 20, 21</sup> While findings from the phase 3 KEEPsAKE 1 and KEEPsAKE 2 studies in patients with active PsA have demonstrated durable efficacy for patients with PsA treated with risankizumab versus placebo, this study utilized multiple outcome measures and pooled data, when available, to assess the impact of treatment with risankizumab over two years, over all 6 GRAPPA domains of PsA, and the PsA-related conditions of IBD and uveitis.

Risankizumab was efficacious in reducing signs and symptoms of peripheral arthritis, including achievement of stringent treatment targets such as DAPSA LDA and remission (68.3% at week 100) and structural non-progression measured at 2 years in KEEPsAKE 1. Evaluated as an outcome measure for axial disease, 57.7% of pooled patients in the continuous risankizumab cohort reported MCID in modified BASDAI at week 100. Among pooled patients in the continuous risankizumab cohort, 57.7% and 76.2% showed resolution of enthesitis and dactylitis, respectively, at week 100.

Achieving comprehensive control across the multiple domains of PsA remains a challenge, with only one-third of treated PsA patients achieving stringent disease control measures such as minimal disease activity or DAPSA LDA.<sup>38</sup> The GRAPPA treatment recommendations take a comprehensive domain-based approach that ensures that both the
primary PsA symptoms and the potential influence of comorbidities are taken into consideration when determining the most appropriate treatment strategy.³ It is noteworthy that not all patients will achieve optimal responses across all disease domains, and in these instances it is important to examine the individual domains of PsA and implement a treatment approach.

While the BASDAI and ASDAS were originally developed for the assessment of axial spondyloarthritis, these tools are frequently used to evaluate axial symptoms in patients with psoriatic arthritis due to the lack of assessment instruments specific to axial psoriatic arthritis. It is important to note that improvements in BASDAI and ASDAS scores may be affected by extra-axial symptoms, such as peripheral arthritis and enthesitis.³⁹ Here we also report modified BASDAI scores aiming to minimize the influence of improvement in peripheral arthritis from the assessment of axial symptoms.

Although IL-23 is indicated to have a pivotal role in the pathogenesis of ankylosing spondylitis (AS), clinical trials involving the IL-23 inhibitors risankizumab and ustekinumab failed to demonstrate efficacy in the treatment of AS.⁴⁰,⁴¹ The phenotypic variability observed in axial PsA suggests these conditions may involve distinct disease processes compared to AS, potentially leading to differences in therapeutic responses. Furthermore, it has been proposed that AS pathogenesis may include an IL-17 production pathway that operates independently of IL-23-mediated stimulation of Th17 cells.⁴²

In separate clinical trials in patients with psoriasis, risankizumab has demonstrated efficacy and complete skin clearance (PASI100) by week 16 that is maintained up to 5 years.⁴³⁻⁴⁹ As reported previously for the UltIMMa-1 and -2, IMMvent, IMMerge, and LIMMitless phase 3 clinical studies, patients with psoriasis treated with risankizumab demonstrated superior efficacy compared with those treated with ustekinumab, secukinumab, or adalimumab.²⁵⁻²⁷,²⁸ In aMM, suboptimal responders to secukinumab or ixekizumab who switched to risankizumab demonstrated improved skin symptoms. In the IMMpulse study, more patients achieved higher treatment targets with risankizumab than with apremilast at week 16 (achievement of PASI100, PASI90 and sPGA 0/1), and on to week 52.²⁹ Meaningful efficacy for skin outcomes was also demonstrated in this post hoc analysis of PsA trials, which showed that 72.7% of patients in the continuous risankizumab cohort in KEEPSAKE 1 achieved absolute PASI ≤ 1 at week 100, and 61.6% achieved “clear” or “minimal” nail psoriasis at week 100.

In separate clinical trial programs including the phase 3 INSPIRE, and phase 3 ADVANCE and MOTIVATE induction trials, risankizumab has demonstrated efficacy in both UC and CD.⁵⁰,⁵¹ In the head-to-head phase 3 SEQUENCE study evaluating the efficacy and safety of risankizumab versus ustekinumab for patients with moderately to severely active CD who had failed one or more TNF inhibitors, risankizumab met both primary endpoints of non-inferiority for clinical remission at week 24 and superiority of endoscopic remission at week 48 as compared to ustekinumab.⁵²

In a retrospective longitudinal study of 406 PsA patients from a single referral hospital, uveitis was prevalent in approximately 5% of patients.⁵³ In patients from the pooled KEEPSAKE studies receiving long-term risankizumab treatment (total risankizumab exposure of 4594 PY), this post hoc analysis reports a relatively lower incidence of uveitis; uveitis was reported in 5 (0.4%; 0.2/100 PY) patients overall, 2 of whom had a history of uveitis. The incidence of uveitis reported for long-term bimekizumab treatment in patients with PsA is 0.2%; 0.1/100 PY (total bimekizumab exposure of 3656 PY and data presented as exposure-adjusted incidence rate (EAIRs); uveitis occurred in 3 patients overall, 1 with a history of uveitis) and the incidence of uveitis reported for long-term upadacitinib treatment in patients with PsA is 0.3%; 0.2/100 PY
In a comparative study of 306 PsA patients from a single university center, IBD was prevalent in 3.3% of patients.⁵⁷ In patients from the pooled KEEPsAKE studies receiving long-term risankizumab treatment (total risankizumab exposure of 4594 PY), this post hoc analysis reports a relatively lower incidence of IBD. IBD was reported in 6 (0.4%; 0.2/100 PY) patients overall, of which 3 patients had a prior history of IBD. IBD incidence reported for long-term bimekizumab treatment in patients with PsA is 0.6%; 0.2/100 PY (total bimekizumab exposure of 3656 PY; IBD occurred in 8 patients overall, 1 with a history of IBD) and the incidence of IBD reported for long-term upadacitinib treatment in patients with PsA is 0.3%; 0.1/100 PY (total upadacitinib exposure of 2426 PY; IBD occurred in 3 patients overall, 2 with a history of IBD).⁵⁵

⁵⁶This post hoc analysis is not without limitations. The participant population across both KEEPsAKE trials have high levels of disease activity, which is typical of a clinical trial population, and may limit the overall applicability of the findings. For outcomes such as resolution of enthesitis and dactylitis and those related to axial disease, the sample sizes of patients with corresponding baseline conditions were relatively smaller than for other outcomes analyzed. Additionally, for patients with psoriatic spondylitis, or axial involvement, not all cases were confirmed by imaging. Outcomes related to IBD and uveitis were limited by the relatively small number of enrolled patients with a history of these conditions. Comorbidities in PsA were not included as part of this study.

Overall, this post hoc analysis demonstrates further that risankizumab delivers durable efficacy across all domains of PsA in patients who are csDMARD-IR and/or bDMARD-IR.

## Acknowledgments

AbbVie and the authors thank the patients, trial sites, and investigators who participated in this study. AbbVie was the study sponsor, contributed to study design, data collection, analysis and interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Amrita Balachandran, PhD, of AbbVie. Editorial support was provided by S. Michael Austin of AbbVie, Inc.

## Disclosures

**Laura C. Coates:** received grants/research support from AbbVie, Amgen, Janssen and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Enlivex, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB; and has been paid as a speaker for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

**Ricardo Blanco:** received grants/research support from AbbVie, Merck, and Roche; and has received consultation fees or honoraria for serving as a speaker for AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche.

**Frank Behrens:** received research grants, honoraria or fees for serving as a consultant or speaker from AbbVie, Acelyrin, Affibody, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, Roche, Sandoz and Sanofi, UCB.

**Alexis Ogdie:** received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Lilly, Novartis, Pfizer, and Takeda, and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, National Psoriasis Foundation, Pfizer, and Novartis.
**Filip Van den Bosch:** received speaker and/or consulting fees from AbbVie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB.

**Roberto Ranza:** consultant for AbbVie, Janssen, Novartis, and Pfizer, and is a member of speaker bureaus for AbbVie, Janssen, Novartis, and Pfizer.

**Yael Klionsky:** received consultancy fees from and/or served on advisory boards for MedIQ, Amgen, AstraZeneca, Johnson and Johnson, and Lilly.

**Ahmed M. Soliman, Michael Chen, Derek Coombs, Linyu Shi, Jamie Urbanik, Thomas Iyile, and Ralph Lippe:** employees of AbbVie, and may hold AbbVie stock, stock options, and/or patents.

**Laure Gossec:** received research grants from AbbVie, Biogen, Eli Lilly, Novartis, UCB; consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, STADA, and UCB.

**Funding**

AbbVie funded the study and had a role in the study design, data collection, data analysis, data interpretation and writing of the report. All authors had access to the relevant data in the study and had final responsibility for the decision to submit for publication.

**Role of authors and sponsor**

AbbVie was the study sponsor, and the study was designed by AbbVie, the authors, and investigators. Clinical data were collected by the investigators, their teams, and AbbVie. AbbVie was involved in data analysis, the interpretation of results and the preparation, review, and approval of the final version of this report. All the authors had access to the data, reviewed, and approved the final version, made the decision to submit the manuscript for publication, and attest to the accuracy and completeness of the data. The corresponding author had access to all relevant data and the final responsibility to submit for publication. A medical writer, employed by AbbVie, assisted with preparing an initial draft under the direction of the authors. R. Lippe, T. Iyile, J. Urbanik, L.C. Coates, L. Gossec, A. Ogie contributed to study conception and design. R. Lippe, T. Iyile, A.M. Soliman, M. Chen, L. Shi, D. Coombs, and J. Urbanik participated in data acquisition. All authors participated in the analysis and interpretation of the data, critically reviewed the manuscript and approved the final version. L.C. Coates is responsible for the overall content as the guarantor.

**Ethics approval**

Studies were conducted per the International Conference on Harmonisation guidelines, applicable regulations, and the Declaration of Helsinki. Study-related documents were approved by independent ethics committees and institutional review boards. All patients provided written, informed consent.

**Data availability statement**

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymised, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be
provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link:

<https://vivli.org/ourmember/abbvie/ then select “Home.”>
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<table><caption>**Table 1. PsA Domains and Outcome Measures Assessed**</caption><thead><tr><th>Domain</th><th>Measure</th><th colspan="3">Week of Assessment</th></tr></thead><tbody><tr><td rowspan="10">Peripheral Arthritis</td><td><strong>Data from patients in KEEPSAKE 1</strong></td><td>Week 24</td><td>Week 52</td><td>Week 100</td></tr><tr><td>No. (%) of patients achieving ACR20</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients maintaining ACR20, ACR50, and ACR70</td><td></td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients in REM/LDA/MDA/HDA based on DAPSA score</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients achieving MCID in pain</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients with no radiographic progression (PsA-mTSS ≤ 0 from baseline)</td><td></td><td></td><td>✓</td></tr><tr><td>No. (%) of patients with no radiographic progression (PsA-mTSS ≤ 0.5 from baseline)</td><td></td><td></td><td>✓</td></tr><tr><td>Change from baseline in SJC66 and TJC68</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients maintaining TJC68 ≤ 1 and SJC66 ≤ 1 response</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td rowspan="3">Enthesitis and Dactylitis</td><td><strong>Pooled data from patients in KEEPSAKE 1 and KEEPSAKE 2</strong></td><td></td><td></td><td></td></tr><tr><td>No. (%) of patients achieving resolution of enthesitis (LEI = 0)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients achieving resolution of dactylitis (LDI = 0)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td rowspan="2">Psoriasis</td><td><strong>Data from patients in KEEPSAKE 1</strong></td><td></td><td></td><td></td></tr><tr><td>No. (%) of patients achieving PASI90 and PASI100</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td rowspan="2">Nail Psoriasis</td><td>No. (%) of patients maintaining PASI90 response</td><td></td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients achieving absolute PASI ≤ 1</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td rowspan="4">Axial Disease</td><td><strong>Data from patients in KEEPSAKE 1</strong></td><td></td><td></td><td></td></tr><tr><td>Change from baseline in mNAPSI</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>Change from baseline in PGA-F</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients achieving “clear” or “minimal” nail psoriasis (PGA-F = 0 or 1 with ≥ 2-grade improvement)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td rowspan="10">EMMs (IBD and Uveitis)</td><td><strong>Pooled data from patients in KEEPSAKE 1 and KEEPSAKE 2</strong></td><td></td><td></td><td></td></tr><tr><td>No. (%) of patients achieving MCID in modified BASDAI (≥ 1.1 decrease from baseline)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>Change from baseline in modified BASDAI</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>Change from baseline in BASDAI Q2 (spinal pain)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>Change from baseline in ASDAS</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>CII in modified BASDAI (no. [%] of patients achieving ≥ 2 decrease from baseline in modified BASDAI among patients with baseline modified BASDAI ≥ 2)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>CII in ASDAS (no. [%] of patients achieving ≥ 1.1 decrease from baseline in ASDAS among patients with baseline ASDAS ≥ 1.1)</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients maintaining MCID in BASDAI (in KEEPSAKE 1)</td><td></td><td>✓</td><td>✓</td></tr><tr><td>No. (%) of patients maintaining MCID in modified BASDAI response (in KEEPSAKE 1)</td><td></td><td>✓</td><td>✓</td></tr><tr><td>Overall number of EMMs including new onset and flares</td><td></td><td></td><td>✓</td></tr><tr><td>New onset cases of IBD and uveitis in patients with no prior history</td><td></td><td></td><td>✓</td></tr><tr><td>Flares in patients with a prior history of IBD and uveitis</td><td></td><td></td><td>✓</td></tr></tbody></table>

ACR20, ACR50, ACR70, ≥ 20%, 50%, or 70% improvement in PsA symptoms using American College of Rheumatology criteria; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity; CII, clinically
important improvement; DAPSA, Disease Activity Index for Psoriatic Arthritis; EMMs, extra-musculoskeletal manifestations; HDA, high disease activity (DAPSA > 28); IBD, inflammatory bowel disease; LEI, Leeds Enthesitis Index; LDI, Leeds Dactylitis Index; MDA, moderate disease activity (14 < DAPSA ≤ 28); MCID, minimal clinically important differences; mTSS, modified Total Sharp Score; PASI, Psoriasis Area and Severity Index; mNAPSI, modified Nail Psoriasis Severity Index; PGA-F, Physician's Global Assessment of Fingernail Psoriasis; REM, remission (DAPSA ≤ 4); SJC66, swollen joint count in 66 joints; TJC68, tender joint count in 68 joints.

<figure><img src="image_2.png" /><figcaption>**Figure 1: Distribution of DAPSA Disease Activity Level Through Week 100 (AO)**</figcaption></figure>

Data for patients in KEEPSAKE 1 and reported as observed.

High is DAPSA > 28, moderate is 14 < DAPSA ≤ 28, low is 4 < DAPSA ≤ 14, remission is DAPSA ≤ 4.

AO, as observed; DAPSA, Disease Activity Index for Psoriatic Arthritis; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
<caption>**Figure 2: Achievement of (A) MCID in Pain<sup>a</sup> Over 100 Weeks (NRI-C/NRI-MI),<sup>b</sup> (B) Structural Non-Progression at Week 100 (AO), and (C) Improvement in Swollen Joint Count and Tender Joint Count Over 100 Weeks (MMRM)**</caption>

<figure><img src="image_3.png" /></figure>

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /></figure>

Data reported for patients in KEEPsAKE 1.

AO, as observed; MCID, minimal clinically important differences; MMRM, mixed effect model repeated measurement; mTSS, modified Total Sharp Score; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

<caption>**Figure 3: Resolution of (A) Enthesitis and (B) Dactylitis Over 100 Weeks (NRI-C/NRI-MI)**</caption>

<footnote><sup>a</sup>For patients with Patient's Assessment of Pain ≥ 10 at baseline. MCID for Patient's Assessment of Pain is ≥ 10-point decrease.</footnote>

<footnote><sup>b</sup>Reported by NRI-C at week 24 and by NRI-MI at week 52 and week 100.</footnote>
A

<figure><img src="image_6.png" /></figure>

B

<figure><img src="image_7.png" /></figure>

Data pooled for patients in KEEPSAKE 1 and KEEPSAKE 2 and reported by NRI-C at week 24 and by NRI-MI at week 52 and week 100.

NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
<caption>Figure 4: Achievement of (A) PASI 100 and (B) Absolute PASI ≤ 1 Over 100 Weeks (NRI-C/NRI-MI)</caption>

A

<figure><img src="image_8.png" /></figure>

B

<figure><img src="image_9.png" /></figure>

<figure><img src="image_10.png" /></figure>

Data reported for patients with BSA ≥ 3% at baseline in KEEPSAKE 1 by NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 at week 24, and by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100.

NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19: NRI-MI, non-responder imputation, multiple imputation; PASI, Psoriasis Area and Severity Index; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
<figure><img src="image_11.png" /><figcaption>**Figure 5: Improvement in Nail Psoriasis Over 100 Weeks (MMRM)**</figcaption></figure>

<figure><img src="image_12.png" /></figure>

Data reported for patients in KEEPSAKE1 with nail psoriasis at baseline. Data for mNAPSI reported by Mixed Effect Model Repeated Measurement (MMRM) analysis and data for PGA-F reported by NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 at week 24, and by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100.

mNAPSI, modified Nail Psoriasis Severity Index; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation, multiple imputation; PGA-F, Physician's Global Assessment of Fingernail Psoriasis; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

<caption>**Figure 6: Achievement of MCID in BASDAI (NRI-C/NRI-MI) and Improvement in BASDAI and ASDAS Scores (MMRM)**</caption>
<figure><img src="image_13.png" /></figure>

MCID defined as ≥ 1.1-point decrease, and N is based on baseline BASDAI ≥ 1.1.

Data pooled for patients with axial involvement at baseline in KEEPSAKE 1 and KEEPSAKE 2.

For MCID in BASDAI, data reported by NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 at week 24, and by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100. For change from baseline in BASDAI, BASDAI spinal pain (question 2), and ASDAS, data is reported by mixed effect model repeated measurement (MMRM).

ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity; MCID, minimal clinically important differences; MMRM, mixed effect model repeated measurement; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

<caption>**Figure 7: Overview of EMMs by History**</caption>
<figure><img src="image_14.png" /></figure>

## Prior History of EMMs Reported at Baseline

<table><thead><tr><th>EMM, n (%)</th><th>RZB 150 mg<br>N = 1365</th></tr></thead><tbody><tr><td>IBD</td><td>10 (0.7)</td></tr><tr><td>Uveitis</td><td>10 (0.7)</td></tr></tbody></table>

Data pooled for KEEPsAKE 1 and KEEPsAKE 2.

EMMs, extra-musculoskeletal manifestations; EAER, exposure-adjusted event rates; IBD, inflammatory bowel disease; PY, patient years; RZB, risankizumab.

## Supplemental Figure 1. Percentage of Patients Maintaining ACR Response Through Week 100 (NRI-MI)
<figure><img src="image_15.png" /></figure>

Data reported for patients in KEEPSAKE 1 by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders.

ACR20, ACR50, ACR70, ≥ 20%, 50%, or 70% improvement in PsA symptoms using American College of Rheumatology criteria; NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
<figure><img src="image_16.png" /></figure>

Data reported for patients in KEEPSAKE 1 by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders.

NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab; SJC, swollen joint count; TJC, tender joint count.

**Supplemental Figure 3.** Percentage of Patients Maintaining Resolution of Enthesitis and Resolution of Dactylitis Through Week 100 (NRI-MI)
<figure><img src="image_17.png" /></figure>

Data pooled for patients in KEEPsAKE 1 and KEEPsAKE 2 and reported by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100.

NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

**Supplemental Figure 4.** Percentage of Patients Maintaining PASI90 Response Through Week 100 (NRI-MI)
<figure><img src="image_18.png" /></figure>

Data reported for patients in KEEPSAKE 1 by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders.

NRI-MI, non-responder imputation, multiple imputation; PASI 90, ≥ 90% improvement in the Psoriasis Area and Severity Index; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
<figure><img src="image_19.png" /></figure>

Data reported for patients in KEEPSAKE1 by Mixed Effect Model Repeated Measurement (MMRM) analysis.

PGA-F, Physician's Global Assessment of Fingernail Psoriasis; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.
A

≥ 2-Point Decrease from Baseline in Modified BASDAI (NRI-C/NRI-MI)

<figure><img src="image_20.png" /></figure>

B

≥ 1.1-Point Decrease from Baseline in ASDAS (NRI-C/NRI-MI)

<figure><img src="image_21.png" /></figure>

Data pooled for patients with axial involvement at baseline in KEEPsAKE 1 and KEEPsAKE 2.

Data reported by NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 at week 24, and by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100.

ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

**Supplemental Figure 7.** Percentage of Patients Achieving MCID in Modified BASDAI Through Week 100
MCID in Modified BASDAI (NRI-C/NRI-MI)

<figure><img src="image_22.png" /></figure>

MCID defined as ≥ 1.1-point decrease, and N is based on baseline modified BASDAI ≥ 1.1.

Data pooled for patients with axial involvement at baseline in KEEPSAKE 1 and KEEPSAKE 2.

Data reported by NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 at week 24, and by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders at week 52 and week 100.

BASDAI, Bath Ankylosing Spondylitis Disease Activity; MCID, minimal clinically important differences; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

**Supplemental Figure 8.** Percentage of Patients Maintaining MCID in BASDAI and Modified BASDAI Through Week 100 (NRI-MI)

A. BASDAI
<figure><img src="image_23.png" /></figure>

## B. Modified BASDAI

<figure><img src="image_24.png" /></figure>

Data reported among week 24/52 responders by AO for patients in KEEPSAKE 1 with spondylitis at baseline, by NRI-MI, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 and geopolitical conflict, and all other missing data treated as non-responders. MCID defined as ≥ 1.1-point decrease, and N is based on baseline BASDAI ≥ 1.1.

BASDAI, Bath Ankylosing Spondylitis Disease Activity; MCID, minimal clinically important differences; NRI-MI, non-responder imputation, multiple imputation; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.

## Supplemental Figure 9. Change From Baseline in Modified BASDAI Through Week 100
<figure><img src="image_25.png" /></figure>

Data pooled for patients with axial involvement at baseline in KEEPsAKE 1 and KEEPsAKE 2.
Data are reported by mixed effect model repeated measurement (MMRM).

BASDAI, Bath Ankylosing Spondylitis Disease Activity; MMRM, mixed effect model repeated measurement; PBO, placebo; PBO/RZB, treatment with placebo to week 24, followed by treatment with risankizumab until week 100; RZB, risankizumab.