NICE guidance - Guselkumab for treating active psoriatic arthritis after inadequate response to DMARDs

Last edited 07/2021 and last reviewed 07/2021

Guselkumab, alone or with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults whose disease has not responded well enough to disease-modifying antirheumatic drugs (DMARDs) or who cannot tolerate them, only if they have:

  • peripheral arthritis with 3 or more tender joints and 3 or more swollen joints
  • moderate to severe psoriasis (a body surface area of at least 3% affected by plaque psoriasis and a Psoriasis Area and Severity Index [PASI] score greater than 10)
  • had 2 conventional DMARDs and at least 1 biological DMARD

Assess the response to guselkumab from 16 weeks. Stop guselkumab at 24 weeks if psoriatic arthritis has not responded adequately using the Psoriatic Arthritis Response Criteria (PsARC; an adequate response is an improvement in at least 2 of the 4 criteria, 1 of which must be joint tenderness or swelling score, with no worsening in any of the 4 criteria). If PsARC response does not justify continuing treatment but there is a PASI 75 response, a dermatologist should decide whether continuing treatment is appropriate based on skin response

Notes:

  • Guselkumab is an interleukin (IL)-23 inhibitor that binds to the p19 subunit of IL-23 that has been shown to be highly efficacious and well tolerated for the treatment of moderate-to-severe plaque psoriasis
    • during the initiation phase of the psoriatic skin lesions, there is an increment of the production of TNF occurs and, as a result, activation of dermal dendritic cells
      • these cells are responsible for the increased production of IL-23 and the subsequent activation of distinct subgroups of IL-17 producing cells
    • Guselkumab prevents the interaction of the IL-23 with its receptor on the surface of the cell
      • this action is responsible for blocking the initiation of the IL-23 pathway and the subsequent release of other proinflammatory cytokines
    • Guselkumab is the first in its class to be approved to treat moderate-to-severe plaque psoriasis
  • efficacy and safety of guselkumab in patients with active psoriatic arthritis were reported in two randomized, phase 3, multicenter, double-blind, placebo-controlled clinical trials (DISCOVER-1 and DISCOVER-2) that had as a primary endpoint of ACR20 response at week 24 (3,4)

Reference:

  • NICE (June 2021). Guselkumab for treating active psoriatic arthritis after inadequate response to DMARDs
  • Galluzzo M, Tofani L, Lombardo P, Petruzzellis A, Silvaggio D, Egan CG, Bianchi L, Talamonti M. Use of Guselkumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: A 1 Year Real-Life Study. J Clin Med. 2020 Jul 9;9(7):2170.
  • Deodhar A, Helliwell PS, Boehncke WH, Kollmeier AP, Hsia EC, Subramanian RA, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNF alpha inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1115-25
  • Mease PJ, Rahman P, Gottlieb AB, Kollmeier AP, Hsia EC, Xu XL, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1126-36.