Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3.
The findings, published inextend the previously published of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.
, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.
The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.
Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.
The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).
At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.
In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.
The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.
No patient developed an opportunistic infection or died during the study period.
The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.
“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.
The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.
SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. .