Impact of guselkumab on health-related quality of life for patients with PsA

Introduction

Guselkumab, which inhibits the p19 subunit of interleukin-23, has been evaluated for the treatment of patients with psoriatic arthritis (PsA). The efficacy and safety of guselkumab was analyzed in the phase III DISCOVER-1 (NCT03162796) and DISCOVER-2 (NCT03158285) trials.^1,2

The DISCOVER-1 trial met its primary endpoint, ACR20 at Week 24 was achieved by 59% of patients treated every 4 weeks and 52% of those treated every 8 weeks, compared with 22% in the placebo group.¹ Similar results were achieved in the phase III DISCOVER -2 trial, with 64% of all patients treated with guselkumab achieving ACR20 response at Week 24 compared with 33% in the placebo group.² As a result of these studies, guselkumab received approvals from the U.S. Food and Drug Administration (FDA) and the European Commission (EC) in 2020.

In a recent analysis by Curtis et al.,³ the impact of guselkumab on health-related quality of life (HRQoL) was assessed in patients with PsA who had not previously received a biologic.

Study design

DISCOVER-2 was a phase III randomized, double-blind, placebo-controlled trial of adults with active PsA (Figure 1).

Active PsA was defined as

• ≥5 swollen joints (swollen joint count);
• ≥5 tender joints (tender joint count; TJC); and
• a ≥0.6 mg/dL C-reactive protein level despite standard therapy.

Figure 1. Study design* 

DMARD, disease-modifying antirheumatic drugs.
*Adapted from Curtis, et al.^3
†DMARD use options: yes or no.

Two instruments, the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and the EuroQol Visual Analog Scale (EQ-VAS), were administered to patients in the DISCOVER-2 trial to assess HRQoL.³

Results

Overall, 739 patients were included in this study with an average age of 45.7 years, 47.5% were female and 98% were White. Patients had a mean swollen joint count (0–66) and tender joint count (0–68) of 12.3 and 21.3, respectively. The average pain score was 6.3/10, with baseline EQ-VAS and EQ-5D-5L scores demonstrating that patients’ HRQoL was greatly impacted at the start of the study. Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), with patients reporting a mean of ~30/52 at baseline.

Table 1. Baseline patient characteristics*

Patients in the guselkumab group demonstrated an improvement from baseline in EQ-5D-5L Index and EQ-VAS scores after 16 weeks, this improvement was maintained through to Week 52 (Figure 2). Patients treated with guselkumab every 8 weeks showed a significant increase compared with the placebo group at Week 16 in both HRQoL scores (EQ-5D-5L, p = 0.0368; EQ-VAS, p = 0.0015). At Week 24, both guselkumab treated groups showed a significant improvement compared with the placebo group (Figure 2).

After Week 24, patients treated with the placebo were allowed to swap to the guselkumab group treated every 4 weeks. Following this treatment change, patients in the crossover group showed an improvement in HRQoL in line with patients originally randomized to receive guselkumab every 4 weeks (66.1 vs 66.2% in EQ-5D-5L and 68.1% vs 67.1% in the EQ-VAS crossover vs guselkumab group treated every 4 weeks, respectively).

Figure 2. Proportion of patients who achieved improvements ≥minimally important difference in A EQ-5D-5L score and B EQ-VAS through to Week 52*

EQ-5D-5L, EuroQol 5-Dimension 5-Level; EQ-VAS, EuroQol Visual Analog Scale; GUS, guselkumab, PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks.
*Adapted from Curtis, et al.^3
†The minimally imporant difference values were 0.07 and 9.68 for EQ-5D-5L and EQ-VAS, respectively.

Multivariate analysis was conducted to assess what clinical features were associated with HRQoL; parameters demonstrating a significant association are detailed in Table 2. FACIT-F and pain scores were significantly associated with both the EQ-5D-5L index and EQ-VAS scores.

Table 2. Multivariate analysis of patient variables with EQ-5D-5L Index and EQ-VAS from baseline to Week 24*

Limitations

The authors noted several limitations of this study, including the impact of specific inclusion criteria in DISCOVER-2 on the generalizability of the findings. The EQ-5D-5L score was translated to an index score between 0−1, with a statistical mapping program that used the US EuroQoL value set; therefore, using values from a different country may give a slightly different result.

Conclusion

Patients treated with 100 mg guselkumab every 4 or 8 weeks in the DISCOVER-2 trial demonstrated an improvement in both HRQoL scoring systems, with benefit seen up to Week 52 of analysis. HRQoL impairment for patients with PsA was associated with C-reactive protein level, fatigue, pain, increased psoriasis symptoms, and swollen/tender joints. Guselkumab treatment resulted in improved clinical symptoms and led to an improvement of HRQoL in patients with PsA.