Sponsored by AbbVie Medical Affairs

The Role of a Selective IL-23 p19 Inhibitor for Patients With Psoriatic Arthritis

JUNE 23, 2022


Risankizumab (RZB) was approved in April 2019 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and was approved in January 2022 for the treatment of adults with active psoriatic arthritis (PsA)1.

Role of IL-23 in Psoriatic Arthritis (PsA): IL-23 Increased in Synovial Tissue, Synovial Fluid, and Entheses

figure 1

IL-23 is a key inflammatory cytokine produced and secreted by dendritic cells and macrophages. IL-23 contributes to the pathogenesis of PsA via multiple pathways.

  • In an IL-17 dependent pathway, IL-23 drives expansion and survival of pathogenetic TH17 cells, driving inflammation in effector tissues like bone, joints, and skin.
  • In an IL-17 independent pathway, IL-23 directly promotes inflammation by stimulating macrophages to release cytokines like IL-1, IL-6, and TNF-α.

The local inflammation from both pathways contributes to the major symptoms of PsA, including bone erosion, synovitis, enthesitis, and psoriasis.

 

The Selective IL-23 Antagonist Risankizumab

Risankizumab Mechanism of Action

Characteristics of Risankizumab1,3
Risankizumab is a humanized mAB of the IgG1 subclass that is directed against the IL-23 cytokine, specifically the p19 subunit, inhibiting its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in the inflammatory and immune response. Risankizumab inhibits the release of pro-inflammatory cytokines and chemokines.

Image 2

IgG1=immunoglobulin G1; mAb=monoclonal antibody; PsA = psoriatic arthritis

1. SKYRIZI® (risankizumab-rzaa) [package insert]. North Chicago, IL: AbbVie Inc.
2. Saxena A et al. In Adebajo et al. (eds.), Psoriatic Arthritis and Psoriasis: Pathology and Clinical Aspects. 2016 https://doi.org/10.1007/978-3-319-19530-8_9.
3. Singh S, et al. mAbs. 2015 7:4, 778-791. doi: 10.1080/19420862.2015/1032491.

KEEPsAKE Trials Overview1,2

The KEEPsAKE program included two phase 3, multicenter, randomized, double-blind, placebo-controlled studies designed to evaluate the safety and efficacy of risankizumab in adult patients with active PsA. The two pivotal studies are:

  • KEEPsAKE 1 (NCT03675308) evaluated patients (placebo [PBO]; N=481, RZB; N=483) with active PsA who had a history of inadequate response to or intolerance to at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD-IR).1
  • KEEPsAKE 2 (NCT03671148) evaluated patients (PBO; N=219, RZB; N=224) who had a history of an inadequate response or intolerance to biological therapy (Bio-IR) and/or csDMARDs (mixed population, ~50% Bio-IR, ~50% csDMARD-IR Population).2

Study Design

figure 3

KEEPsAKE 1 bilateral radiographs of hand and feet included at screening, baseline, Week 24, and Week 52.

OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

*The first n value is for KEEPsAKE 1; the second n value is for KEEPsAKE 2. †At week 16, subjects classified as nonresponders (defined as not achieving at least a 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy. ‡Starting at Week 36, subjects classified as nonresponders were discontinued from study drug.

1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi: 10.1136/annrheumdis-2021-221019.
2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi: 10.1136/annrheumdis-2021-221048.

     

    KEEPsAKE 1 and KEEPsAKE 2: Baseline Characteristics1-3

    image 4

    *Axial involvement was either imaging (radiographs and/or MRI) confirmed or investigator reported.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi: 10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi: 10.1136/annrheumdis-2021-221048.
    3. Data on file, AbbVie Inc. ABVRRTI73417.

    Risankizumab Efficacy

    Proportion of Patients Achieving ACR20 Through Week 52 in KEEPsAKE 1 and KEEPsAKE 21-4

    image 5

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi: 10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi: 10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.

     

    Proportion of Patients Achieving ACR50 Through Week 52 in KEEPsAKE 1 and KEEPsAKE 21-4

    image 6

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    Non-ranked secondary endpoints were not controlled for multiplicity.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.

     

    Proportion of Patients Achieving ACR70 Through Week 52 in KEEPsAKE 1 and KEEPsAKE 21-4

    image 7

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    Non-ranked secondary endpoints were not controlled for multiplicity.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.

     

    Proportion of Patients Achieving Minimal Disease Activity (MDA) at Week 24 and Week 52 in KEEPsAKE 1 and KEEPsAKE 21-7

    image 8

    MDA is achieved when meeting 5 or more of the 7 criteria:

    • Tender joint count 1 
    • Swollen joint count 1
    • Enthesitis count 1
    • PASI 1 or BSA 3
    • Patient global assessment of disease activity VAS 20 mm
    • Patient Assessment of Pain VAS 15 mm
    • HAQ-DI 0.5

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.

    HAQ-Dl=Health Assessment Questionnaire–Disability Index. VAS=visual analog scale.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.
    5. Data on File. AbbVie. ABVRRT173276.
    6. Data on File. AbbVie. ABVRRT173305.
    7. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69(1):48-53. doi:10.1136/ard.2008.102053.

     

    Proportion of Patients Achieving Psoriasis Area Severity Index (PASI) 90 Through Week 52 in KEEPsAKE 1 and KEEPsAKE 21-4

    image 9

    Only in patients with coexistent plaque psoriasis (BSA ≥ 3%) at baseline. 

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.


    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.

     

    KEEPsAKE 1 and KEEPsAKE 2: Resolution of Enthesitis and Dactylitis at Week 24 and Week 52 (Pooled)1-4

    image 10

    For subjects with baseline presence of enthesitis (LEI >0).       
    For subjects with baseline presence of dactylitis (LDI >0).

    OLE Limitation: There is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.

    At Week 16, subjects classified as nonresponders (defined as not achieving at least 20% improvement in either or both tender joint count [TJC] and swollen joint count [SJC] at both Week 12 and Week 16 compared to baseline) had the option to add or modify rescue concomitant medications/therapy.

    LEl=Leeds Enthesitis Index. LDl=Leeds Dactylitis Index.

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.

    Risankizumab Safety in Psoriasis and Psoriatic Arthritis1

    Common Adverse Events Through 16 Weeks in Psoriasis

    INTEGRATED SAFETY DATA FOR FIRST 16 WEEKS IN PSORIASIS

    image 11

    Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were similar to those observed during the first 16 weeks of treatment.

    SAFETY DATA FOR PSORIATIC ARTHRITIS

    The overall safety profile observed in subjects with psoriatic arthritis treated with risankizumab is generally consistent with the safety profile in subjects with plaque psoriasis.
    In addition:

    • The incidence of hepatic events was higher in the risankizumab group (5.4%, 16.7 E/100 PYs) compared to the placebo group (3.9%, 12.6 E/100 PYs).
    • The incidence of hypersensitivity reactions was higher in the risankizumab group (n=16, 2.3%) compared to the placebo group (n=9, 1.3%).

    †Includes: respiratory tract infection (viral, bacterial, or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsilitis. ‡Includes: headache, tension headache, sinus headache, cervicogenic headache. §Includes: fatigue, asthenia. ‖Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation, irritation, pain, pruritus, reaction, swelling, warmth. ¶Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection, onychomycosis.

    1. SKYRIZI® (risankizumab-rzaa) [package insert]. North Chicago, IL: AbbVie Inc.

     

    Treatment Emergent Adverse Events of Interest in KEEPsAKE 1 and KEEPsAKE 2 Through Week 521-5

    figure 12

    RZB may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, discontinue RZB until the infection resolves. Evaluate patient for TB infection prior to initiating treatment with RZB.

    aSafety reported through data cutoff date (19 April 2021), which includes data through Week 52. Data are from any RZB 150-mg group that includes all patients who receive RZB 150 mg, including those who started on RZB 150 mg at randomization and who switched from placebo to RZB 150 mg after Week 24. b10 of the 27 events were cases of COVID-19. cAn 81-year-old male patient randomized to RZB died of urosepsis on day 96, and a 41-year-old male patient randomized to RZB experienced sudden death on day 502.

    AE = adverse event. E/100 PYs = events per 100 patient years. HZ = herpes zoster. MACE = major adverse cardiovascular events. PY = patient years. TB = tuberculosis. TEAE = treatment-emergent adverse event (defined as an adverse event with an onset date that is on or after the first dose of RZB and up to 140 days after the last dose of RZB if patient discontinued study drug prematurely).

    1. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81:225-231. doi:10.1136/annrheumdis-2021-221019.
    2. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81:351-358. doi:10.1136/annrheumdis-2021-221048.
    3. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 1. Poster presented at: Fall Clinical Dermatology Conference (hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-380.
    4. Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPsAKE 2. Poster presented at: Fall Clinical Dermatology Conference {hybrid meeting); October 21-24, 2021; Las Vegas, NV. 44896-AV-20003-381.
    5. Data on File, AbbVie Inc, ABVRRTI73417.

    Risankizumab-rzaa Indications & Important Safety Considerations

    Indications

    Risankizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

    Risankizumab is indicated for the treatment of active psoriatic arthritis in adults.

    Contraindications

    Risankizumab is contraindicated in patients with a history of serious hypersensitivity reactions to risankizumab or any of the excipients.

    Serious Hypersensitivity Reactions

    Serious hypersensitivity reactions including anaphylaxis may occur. If a serious hypersensitivity reaction occurs, discontinue risankizumab and initiate appropriate therapy immediately.

    Infection

    Risankizumab may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, discontinue risankizumab until the infection resolves.

    Tuberculosis (TB)

    Evaluate patients for tuberculosis infection prior to initiating treatment with risankizumab.

    Administration of Vaccines

    Avoid use of live vaccines in patients treated with risankizumab.

    Common Adverse Reactions

    The most common adverse reactions (≥1%) are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.

     

    Review accompanying risankizumab-rzaa full Prescribing Information.
    For additional information, visit www.rxabbvie.com or contact AbbVie medical information at 1-800-633-9110.


    Content developed by AbbVie Inc. This content is intended for US/Puerto Rico Health Care Professionals.
    The US Medical Affairs department of AbbVie Inc. is the copyright owner of this presentation and has paid Consultant360 to host this content.
    AbbVie is solely responsible for all written and oral content within this presentation.
    ©2022 AbbVie Inc. All rights reserved.

    AbbVie Inc. RISN-US-00009-MC v1.0 07/2022