Results demonstrate that guselkumab was well-tolerated in studies continuing for 1 to 2 years among patients with active psoriatic arthritis regardless of TNFi experience.
Pooled data from several phase 2 and 3 studies showed that the safety profile of guselkumab in tumor necrosis factor inhibitor (TNF)-experienced patients with psoriatic arthritis (PsA) was similar to TNF-naïve patients, which remained favorable for up to 2 years, according to a study published in The Journal of Rheumatology.1
While TNF have been the first-line biologic option for these patients, failure to achieve response can occur and response rates may decline with multiple TNF drugs. Further, TNF therapy may not be appropriate first-line choices for all patients.2
“Safety data, particularly long term, are critical for treatment of a chronic disease such as PsA,” Proton Rahman, MD, of the Craig L Dobbin Genetics Research Centre, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, in Canada, and a team of investigators, wrote. “Thus, it is important to investigate the long-term safety of these therapies in patients with PsA. Additionally, evaluation of safety is essential in the context of prior TNF therapy, which may result in sustained safety concerns or represent a population with a higher inflammatory burden, as well as in patients receiving concomitant methotrexate, which has its own safety profile.”
The DISCOVER-1, DISCOVER-2, and COSMOS studies were used to evaluate the safety and efficacy of guselkumab in TNF-experienced patients with active PsA. Patients in DISCOVER-2 were TNF-naïve, patients were TNF-experienced in the COSMOS trial, and both TNF-naïve and -experienced were enrolled in the DISCOVER-1 study. Eligible patients were randomized to receive guselkumab 100 mg every 4 (Q4W) or 8 (Q8W) weeks or placebo (PBO) with a crossover to guselkumab Q4W or Q8W at week 24.
Adverse event (AE) rates, which were defined as events/100 patient-years (PY), and clinical laboratory findings were determined during the PBO-controlled period as well as through the end of study. AEs of interest included infections, opportunistic infections, serious infections, and serious adverse events (SAEs) of the gastrointestinal, malignancies, and major adverse cardiovascular events (MACE).
Of the 1554 patients included in the studies, 1138 (73.23%) were TNF-naïve and 416 (26.77%) were TNF-experienced. The cohort included 373 patients in the Q4W group, 664 in the Q8W group, and 517 in the PBO group. Baseline demographics and disease characteristics were similar regardless of TNF history.
AE rates at week 24 were 220.8/100 PY in TNF-naïve patients and 251.6/100 PT for TNF-experienced patients for those in the Combined guselkumab group and 196.1/100 PY for TNF-naïve patients and 303.0/100 PY for TNF-experienced patients in the PBO cohort.
All guselkumab-treated patients, including crossover patients from the PBO group, reported low AE rates that were maintained during the long-term evaluation for both TNF-naïve and -experienced groups (139.7/100 PY and 174.0/100 PY, respectively).
Infections were the most common type of AE and included nasopharyngitis and upper respiratory tract infection. These occurred at comparable rates across treatment groups. AEs that led to treatment discontinuation, SAEs, other AEs of interest, increased hepatic transimase levels, and decreased neutrophil counts were similar between guselkumab-treated patients and the PBO group through week 24, regardless of TNF use. These rates remained low through the end of the ≤ 2-year studies.
Limitations included a lack of comparator group after the first 24 weeks and the fact that DISCOVER-2 was the only trial to follow patients for 2 years. Further, the studies were not designed to compare the safety by TNF history or concomitant methotrexate use.
“These results demonstrate that guselkumab was well tolerated in studies continuing for 1 to 2 years among patients with active PsA regardless of TNF experience and concomitant methotrexate use, making the findings relevant to the PsA population in a clinical setting,” investigators concluded. “Together with the robust efficacy data, these results further support the long-term use of guselkumab as an initial biologic therapy or in those who have failed or were intolerant to TNF treatment.”