[Artikelen] Guselkumab bij biologisch naïeve patiënten met actieve artritis psoriatica (DISCOVER-2): een dubbelblinde, gerandomiseerde, placebogecontroleerde fase 3-studi

[Artikelen] Guselkumab bij biologisch naïeve patiënten met actieve artritis psoriatica (DISCOVER-2): een dubbelblinde, gerandomiseerde, placebogecontroleerde fase 3-studi

maart 30, 2020 0 Door admin

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Summary

Background

The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis.

Methods

This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at

ClinicalTrials.gov

,

NCT03158285

(active, not recruiting).

Findings

From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p

Interpretation

Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine’s p19 subunit, was efficacious and demonstrated an acceptable benefit–risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis.

Funding

Janssen Research and Development.

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References

  1. 1.
    • Gottlieb A
    • Merola JF

    Psoriatic arthritis for dermatologists.

    J Dermatolog Treat. 2019; ()

  2. 2.
    • Sherlock JP
    • Joyce-Shaikh B
    • Turner SP
    • et al.

    IL-23 induces spondyloarthropathy by acting on ROR-γt CD3 CD4-CD8- entheseal resident T cells.

    Nat Med. 2012; 18: 1069-1076

  3. 3.
    • Oppmann B
    • Lesley R
    • Blom B
    • et al.

    Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

    Immunity. 2000; 13: 715-725

  4. 4.
    • Murphy CA
    • Langrish CL
    • Chen Y
    • et al.

    Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation.

    J Exp Med. 2003; 198: 1951-1957

  5. 5.
    • Schurich A
    • Raine C
    • Morris V
    • Ciurtin C

    The role of IL-12/23 in T cell-related chronic inflammation: implications of immunodeficiency and therapeutic blockade.

    Rheumatology (Oxford). 2018; 57: 246-254

  6. 6.
    • Kopp T
    • Lenz P
    • Bello-Fernandez C
    • Kastelein RA
    • Kupper TS
    • Stingl G

    IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity.

    J Immunol. 2003; 170: 5438-5444

  7. 7.
    • Blauvelt A
    • Papp KA
    • Griffiths CEM
    • et al.

    Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial.

    J Am Acad Dermatol. 2017; 76: 405-417

  8. 8.
    • Papp KA
    • Blauvelt A
    • Bukhalo M
    • et al.

    Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis.

    N Engl J Med. 2017; 376: 1551-1560

  9. 9.
    • Reich K
    • Armstrong AW
    • Foley P
    • et al.

    Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial.

    J Am Acad Dermatol. 2017; 76: 418-431

  10. 10.
    • Reich K
    • Armstrong AW
    • Langley RG
    • et al.

    Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial.

    Lancet. 2019; 394: 831-839

  11. 11.
    • Deodhar A
    • Gottlieb AB
    • Boehncke W-H
    • et al.

    Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study.

    Lancet. 2018; 391: 2213-2224

  12. 12.
    • Deodhar A
    • Helliwell PS
    • Boehncke W-H
    • et al.

    Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial.

    Lancet. 2020; ()

  13. 13.
    • Taylor W
    • Gladman D
    • Helliwell P
    • Marchesoni A
    • Mease P
    • Mielants H

    Classification criteria for psoriatic arthritis: development of new criteria from a large international study.

    Arthritis Rheum. 2006; 54: 2665-2673

  14. 14.
    • van der Heijde D
    • Sharp J
    • Wassenberg S
    • Gladman DD

    Psoriatic arthritis imaging: a review of scoring methods.

    Ann Rheum Dis. 2005; 64: ii61-ii64

  15. 15.
    • Husni ME
    • Merola JF
    • Davin S

    The psychosocial burden of psoriatic arthritis.

    Semin Arthritis Rheum. 2017; 47: 351-360

  16. 16.
    • Lee S
    • Mendelsohn A
    • Sarnes E

    The burden of psoriatic arthritis: a literature review from a global health systems perspective.

    P T. 2010; 35: 680-689

  17. 17.
    • Lubrano E
    • Perrotta FM

    Beyond TNF inhibitors: new pathways and emerging treatments for psoriatic arthritis.

    Drugs. 2016; 76: 663-673

  18. 18.
    • Langrish CL
    • Chen Y
    • Blumenschein WM
    • et al.

    IL-23 drives a pathogenic T cell population that induces autoimmune inflammation.

    J Exp Med. 2005; 201: 233-240

  19. 19.
    • Zheng Y
    • Danilenko DM
    • Valdez P
    • et al.

    Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis.

    Nature. 2007; 445: 648-651

  20. 20.
    • El-Behi M
    • Ciric B
    • Dai H
    • et al.

    The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.

    Nat Immunol. 2011; 12: 568-575

  21. 21.
    • Codarri L
    • Gyülvészi G
    • Tosevski V
    • et al.

    RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation.

    Nat Immunol. 2011; 12: 560-567

  22. 22.
    • Siebert S
    • Loza MJ
    • Song Q
    • McInnes I
    • Sweet K

    Ustekinumab and guselkumab treatment results in differences in serum IL17A, IL17F and CRP levels in psoriatic arthritis patients: a comparison from ustekinumab Ph3 and guselkumab Ph2 programs.

    Ann Rheum Dis. 2019; 78: a293

  23. 23.
    • Lee Y

    The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases.

    BMB Rep. 2013; 46: 479-483

  24. 24.
    • Reich K
    • Papp KA
    • Armstrong AW
    • et al.

    Safety of guselkumab in patients with moderate-to-severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies.

    Br J Dermatol. 2019; 180: 1039-1049

  25. 25.
    • Griffiths CEM
    • Papp KA
    • Song M
    • et al.

    Maintenance of response with up to 4 years of continuous guselkumab treatment: results from the VOYAGE 1 phase 3 trial.

    Skin. 2019; 3 : 202

  26. 26.
    • Mease P
    • Hall S
    • FitzGerald O
    • et al.

    Tofacitinib or adalimumab versus placebo for psoriatic arthritis.

    N Engl J Med. 2017; 377: 1537-1550

  27. 27.
    • Coates LC
    • Kishimoto M
    • Gottlieb A
    • et al.

    Ixekizumab efficacy and safety with and without concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) in biologic DMARD (bDMARD)-naive patients with active psoriatic arthritis (PsA): results from SPIRIT-P1.

    RMD Open. 2017; 3e000567

  28. 28.
    • Mease PJ
    • Coates LC

    Considerations for the definition of remission criteria in psoriatic arthritis.

    Semin Arthritis Rheum. 2018; 47: 786-796

Article Info

Publication History

Published: March 13, 2020

Identification

DOI: https://doi.org/10.1016/S0140-6736(20)30263-4

Copyright

© 2020 Elsevier Ltd. All rights reserved.

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