Guselkumab (GUS) is a subcutaneously administered monoclonal antibody that targets interleukin (IL) 23.1 It is being investigated in a Phase 2 study to treat rheumatoid arthritis (RA) and moderate to severe plaque psoriasis (PsA).
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On June 11, 2015, at the 2015 meeting of the European League Against Rheumatism (EULAR) in Rome, researchers presented an evaluation of the safety and efficacy of treating patients with active RA (n = 274) with guselkumab or ustekinumab, despite methotrexate (MTX) treatment. This randomized, multicenter, double-blind, placebo-controlled, parallel group study involved patients with six or more tender joints (TJC) and six swollen joints (SJC) with a CRP of at least 0.80 mg/dL.2 Randomized patients received placebo; ustekinumab (UST) 90 mg on Weeks 0, 4 and then every eight weeks; UST 90 mg on Weeks 0, 4 and then every 12 weeks; GUS 200 mg on Weeks 0, 4 and then every eight weeks; or GUS 50 mg on Weeks 0, 4 and then every eight weeks. MTX doses ranged from 10–25 mg weekly and had to be stable for a minimum of 12 weeks prior to randomization. Prednisone 10 mg daily or less, and non-steroidal antiinflammatory agents were permitted.
Placebo-treated patients at Week 12 were given UST 90 mg on Weeks 16, 20 and 28 if they did not have at least a 10% improvement in both TJC and SJC. The number of patients obtaining an ACR20 was not significantly different between the groups.
Some differences were noted in secondary endpoints. More than one treatment-emergent adverse event (TEAE) occurred at Week 48 for 46% of placebo-treated patients, 50% of combined UST-treated patients and 43% of combined GUS-treated patients. There were also two cases of malignancy, squamous cell lung cancer in one UST 90 mg every 12 weeks-treated patient, and breast cancer in one GUS 200 mg every eight weeks-treated patient. ACR20 efficacy at Week 28 was not seen in GUS- or UST-treated patients with active RA.
Minor improvements were seen in some secondary endpoints. These results show that IL-12 and/or IL-23 inhibition lack sign and symptom alleviation in patients with active RA. GUS is currently in Phase 3 clinical trials for the treatment of moderate to severe plaque psoriasis in both the U.S. and European Union.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Johnson & Johnson. News release: Anti-interleukin-23 monoclonal antibody guselkumab shows significant efficacy in treatment of moderate to severe plaque psoriasis. 24 March 2014.
- Smolen J, Agarwal SK, Llivanova E, et al. A Phase 2 study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis. 2015;74(Suppl2):76–77. doi: 10.1136/annrheumdis-2015-eular.3989