Guselkumab provides sustained improvements through 1 year in biologic-naive patients with active psoriatic arthritis (PsA), according to study results published in Arthritis & Rheumatology.
The 24-week placebo-controlled arms of the DISCOVER-1 and DISCOVER-2 trials showed that treatment with guselkumab, a human monoclonal antibody specific to interleukin (IL)-23p19, was safe and effective in biologic-naive patients with PsA. The objective of the current study was to report on the 1-year results of the DISCOVER-2 trial.
In the DISCOVER-2 trial (Clinicaltrials.gov Identifier: NCT03158285), the researchers enrolled 739 adults (52% men) with active PsA, despite standard nonbiologic treatment. All participants were naive to biologic agents and Janus kinase inhibitors. Participants were randomly assigned 1:1:1 to receive subcutaneous guselkumab 100 mg every 4 weeks (n=245); guselkumab 100 mg every 8 weeks (n=248); or placebo every 4 weeks (n=246) until starting guselkumab 100 mg every 4 weeks at 24 weeks. A total of 689 patients (93%) completed the 52-week study.
The primary end point of the DISCOVER-2 trial was met; improvement of 20% or more from baseline in American College of Rheumatology criteria (ACR20) response was significantly more common in patients who received guselkumab every 4 weeks (64%) or every 8 weeks (64%) than placebo (33%) after 24 weeks (P <.0001 for both). At week 52, there were numerical increases in the percentage of patients achieving ACR20 response: 71% of patients who received guselkumab every 4 weeks and 75% of those who received guselkumab every 8 weeks. Similarly, approximately 50% of patients who received guselkumab achieved ACR50 response and more than one-quarter of patients achieved ACR70 at 52 weeks.
Limited radiographic progression and significant improvements from baseline in measures of physical function and quality of life were recorded after 24 weeks in patients who continued receiving guselkumab every 4 or 8 weeks and in those who were initiated with guselkumab every 4 weeks at 24 weeks.
Based on data from both the DISCOVER-1 and DISCOVER-2 trials, resolution of dactylitis was achieved in 75% of patients who received guselkumab every 4 or 8 weeks, and resolution of enthesitis was recorded in 58% of patients.
The most common adverse events included upper respiratory tract infection (7% with guselkumab every 4 weeks; 7% with guselkumab every 8 weeks), nasopharyngitis (7% and 8%, respectively), bronchitis (6% and 2%, respectively), increased alanine aminotransferase (12% and 9%, respectively), and increased aspartate aminotransferase (7% and 7%, respectively). These rates were similar to those seen in the previously published 24-week data.
Serious adverse events were reported in 4% of patients treated with guselkumab, with no difference between the 2 active treatment regimens. Serious adverse events included lower limb fracture, goiter, pneumonia and pulmonary embolism. No deaths occurred throughout the follow-up period. Approximately 2% of patients who received guselkumab and those who received placebo discontinued their treatments because of adverse events.
The study had several limitations, including shorter duration of placebo than active treatment, missing data, lack of adjustment of joint counts for the presence of dactylitis, and the relatively limited follow-up to assess retention and safety or structural damage and disability.
“Guselkumab 100 mg [every 4 weeks] and [every 8 weeks] effectively treated the diverse manifestations of active PsA in biologic-naive patients. The overall treatment effect observed during the 24-week placebo-controlled period was well maintained, and the benefit-risk profile remained favorable for both guselkumab regimens, through week 52 of DISCOVER-2,” the study authors concluded.
Disclosure: This clinical trial was supported by Janssen Research & Development. Please see the original reference for a full list of authors’ disclosures.
McInnes IB, Rahman P, Gottlieb AB, et al. Efficacy and safety of guselkumab, an interleukin-23p19-specific monoclonal antibody, through 1 year in biologic-naïve psoriatic arthritis patients. Arthritis Rheumatol. Published online October 11, 2020. doi:10.1002/art.41553