Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis

Abstract

Introduction: The benefit/risk profiles of biologics can be affected by comorbidities, certain demographic characteristics, and concomitant medications; therefore, it is important to evaluate the long-term safety profiles of biologics across broad patient populations. Guselkumab was well tolerated and efficacious across individual pivotal clinical studies in adults with moderate-to-severe psoriasis and/or active psoriatic arthritis (PsA).

Objectives: The objective of the current analysis was to evaluate guselkumab safety in a large population of patients with psoriatic disease by pooling adverse event (AE) data from 11 phase II/III studies (seven in psoriasis; four in PsA).

Methods: Guselkumab was generally administered as 100 mg subcutaneous injections at Week 0, Week 4, then every 8 weeks (Q8W) in psoriasis studies and at Week 0, Week 4, then every 4 weeks (Q4W) or Q8W in PsA studies. Safety data were summarized for the placebo-controlled period (Weeks 0-16 in psoriasis; Weeks 0-24 in PsA) and through the end of the reporting period (up to 5 years in psoriasis; up to 2 years in PsA). Using the integrated data, incidence rates of key AEs were determined post hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PYs). AE rates were also determined in subgroups of patients defined by sex, age, body mass index (BMI), and prior biologic use.

Results: During the placebo-controlled period, 1061 patients received placebo (395 PYs) and 2257 received guselkumab (856 PYs). Through the end of the reporting period, 4399 guselkumab-treated patients contributed 10,787 PYs of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of AEs were 281 versus 272/100 PYs, and infections were 76.0 versus 72.2/100 PYs. Rates of serious AEs (5.6 vs. 7.8/100 PYs), AEs leading to discontinuation (4.9 vs. 6.6/100 PYs), serious infections (1.0 vs. 2.3/100 PYs), malignancy (0.59 vs. 0.25 patients/100 PYs), and major adverse cardiovascular events (MACE; 0.35 vs. 0.25/100 PYs) were low and comparable between guselkumab and placebo. Among guselkumab-treated patients, safety event rates through the end of the reporting period were numerically lower than or comparable with rates observed during the placebo-controlled period: AEs, 164/100 PYs; infections, 61.2/100 PYs; serious AEs, 5.4/100 PYs; AEs leading to discontinuation, 1.8/100 PYs; serious infections, 1.0/100 PYs; malignancy, 0.6/100 PYs; and MACE, 0.3/100 PYs. No AEs of Crohn's disease, ulcerative colitis, or active tuberculosis were reported among guselkumab-treated patients. In the psoriasis studies, no opportunistic infections were reported among guselkumab-treated patients. Three AEs of opportunistic infections were reported in guselkumab-treated patients with PsA (0.14/100 PYs; all after Week 52 in DISCOVER-2). AE rates were largely consistent across subgroups of guselkumab-treated patients defined by sex, age, BMI, and prior biologic use.

Conclusions: In this analysis of 4399 guselkumab-treated patients with psoriatic disease followed for 10,787 PYs, guselkumab had a favorable AE profile. AE rates were similar between guselkumab- and placebo-treated patients and were consistent throughout long-term guselkumab treatment and across broad subgroups of patients with psoriatic disease.

Clinical trials registrations: Clinicaltrials.gov identifiers: NCT01483599, NCT02207231, NCT02207244, NCT02203032, NCT02905331, NCT03090100, NCT02325219, NCT02319759, NCT03162796, NCT03158285, and NCT03796858.

Fig. 1

Study designs. ADA adalimumab, GUS guselkumab, N total number of patients exposed to GUS in each study, NR nonresponders, PASI Psoriasis Area and Severity Index, PBO placebo, Ph phase, PsA psoriatic arthritis, Q4/8W every 4/8 weeks, R responders, W week

Fig. 2

Rates of SAEs stratified by baseline characteristics [events/100 PYs (95% CI)] in the pooled psoriasis + PsA population^a. ^aCIs based on an exact method assuming that the observed number of events follows a Poisson distribution. Events are counted only once if events were started from the same date with the same derived term. ^bIncludes patients who discontinued study treatment early, with the last study treatment (PBO or GUS) administered prior to W16/24, and who did not receive any study agent (PBO or GUS) at or after W16/24; all data including the final safety follow-up visit collected through up to 2 years were included in this period. ^cOnly includes data prior to administration of GUS in PBO patients who switched from PBO to GUS. ^dOnly includes data after administration of GUS in PBO patients who switched from PBO to GUS. BMI body mass index (under/normal weight: < 18.5–24.9 kg/m²; overweight: 25.0–29.9 kg/m²; obese: 30.0–34.9 kg/m²), CI confidence interval, GUS guselkumab, PsA psoriatic arthritis, PBO placebo, PYs patient-years, SAEs serious adverse events, W week

Fig. 3

Rates of infections and serious infections stratified by baseline characteristics [events/100 PYs (95% CI)] in the pooled psoriasis + PsA population^a. ^aCIs based on an exact method assuming that the observed number of events follows a Poisson distribution. Events are counted only once if events were started from the same date with the same derived term.. ^bIncludes patients who discontinued study treatment early, with the last study treatment (PBO or GUS) administered prior to W16/24, and who did not receive any study agent (PBO or GUS) at or after W16/24; all data including the final safety follow-up visit collected through up to 2 years were included in this period. ^cOnly includes data prior to administration of GUS in PBO patients who switched from PBO to GUS. ^dOnly includes data after administration of GUS in PBO patients who switched from PBO to GUS. ^eInfections were defined by clinician review in COSMOS and by infection flag in all other studies. BMI body mass index (under/normal weight: <18.5–24.9 kg/m²; overweight: 25.0–29.9 kg/m²; obese: 30.0–34.9 kg/m²), CI confidence interval, GUS guselkumab, PsA psoriatic arthritis, PBO placebo, PYs patient-years, W week