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2022-11-22T14:58:29.000Z

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

Nov 22, 2022
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Learning objective: After reading this article, learners will be able to cite a new development in psoriatic arthritis.

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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*

Characteristic

Guselkumab
100 mg every 4 weeks (n = 245)

Guselkumab
100 mg every 8 weeks (n = 248)

Placebo
(n = 246)

All patients
(N = 739)

Age, years

45.9 (11.5)

44.9 (11.9)

46.3 (11.7)

45.7 (11.7)

Female, %

42.0

48.0

52.4

47.5

White, %

98.8

96.8

98.4

98.0

BMI, kg/m2

29.1 (5.9)

28.7 (6.3)

29.0 (6.4)

28.9 (6.2)

PsA disease duration, years

5.5 (5.9)

5.1 (5.5)

5.8 (5.6)

5.5 (5.7)

SJC, mean (SD)

12.9 (7.8)

11.7 (6.8)

12.3 (6.9)

12.3 (7.2)

TJC, mean (SD)

22.4 (13.5)

19.8 (11.9)

21.6 (13.1)

21.3 (12.9)

Patient pain score, mean (SD)

6.2 (2.0)

6.3 (2.0)

6.3 (1.8)

6.3 (1.9)

HAQ-DI, mean (SD)

1.2 (0.6)

1.3 (0.6)

1.3 (0.6)

1.3 (0.6)§

Median CRP level, mg/dL

1.2

1.3

1.2

1.2

Enthesitis, %

170 (69.4)

158 (63.7)

178 (72.7)

506 (68.6)§

Dactylitis, %

121 (49.4)

111 (44.8)

99 (40.4)

331 (44.9)§

PASI, mean (SD)

10.8 (11.7)

9.7 (11.7)

9.3 (9.8)

9.9 (11.1)§

IGA psoriasis total score ≥2, %

201 (82.0)

195 (78.6)

209 (85.3)

605 (82.0)§

EQ-5D-5L Index, mean (SD)

0.6 (0.1)

0.6 (0.2)

0.6 (0.1)

0.6 (0.1)§

EQ-VAS, mean (SD)

46.9 (20.1)

44.5 (19.8)

42.5 (19.2)

44.6 (19.7)§

FACIT-F, mean (SD)

30.8 (9.6)

29.3 (9.9)

29.1 (9.5)

29.7 (9.7)§

SF-36 PCS score, mean (SD)#

33.3 (7.1)

32.6 (7.9)

32.4 (7.0)

32.8 (7.3)§

SF-36 MCS score, mean (SD)#

48.4 (11.0)

47.4 (10.8)

47.2 (12.0)

47.7 (11.3)§

BMI, body mass index; CRP, C-reactive protein; EQ-5D-5L, EuroQol 5-Dimension 5-Level; EQ-VAS, EuroQol Visual Analog Scale; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; HAQ-DI, Health Assessment Questionnaire–Disability Index; IGA Investigator’s Global Assessment, MCS mental component summary, PASI Psoriasis Area and Severity Index, PsA psoriatic arthritis, PCS physical component summary, SD, standard deviation; SF-36, 36-Item Short Form Health Survey; SJC swollen joint count, TJC tender joint count, VAS visual analog scale.
*Adapted from Curtis, et al.3
Patient pain score was measured from 0–10 VAS; HAQ-DI was measured from 0–3; PASI was measured from 0–72; FACIT-F was measured from 0–52.
n = 245.
§ n = 738.
0–1; US population norm = 0.9.
0–100; US population norm = 79.3.
# US population norm = 50.0.

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*

Parameter

EQ-5D-5L Index

EQ-VAS

Estimate

p value

Estimate

p value

CRP, mg/dL

-0.005

<0.0001

-0.51

0.007

FACIT-F

0.007

<0.0001

0.57

<0.0001

Pain

-0.02

<0.0001

-3.47

<0.0001

PASI§

-0.0005

0.03

-0.17

0.0001

SJC

-0.0005

0.21

-0.17

0.02

TJC

-0.0005

0.04

-0.04

0.41

Dactylitis

0.01

0.02

1.74

0.49

CRP, C-reactive protein; EQ-5D-5L, EuroQol 5-Dimension 5-Level; EQ-VAS, EuroQol Visual Analog Scale; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; MMRM, mixed-effects models for repeated measures; PASI, Psoriasis Area and Severity Index; SJC, swollen joint count; TJC, tender joint count.
0–52.
0–10.
§0–72.
0–66.
0–68.

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.

  1. Deodhar A, Helliwell PS, Beohncke WF, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1115-1125. DOI: 1016/S0140-6736(20)30265-8
  2. Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1126-1136. DOI: 1016/S0140-6736(20)30263-4
  3. Curtis JR, McInnes IB, Rahman P, et al. The effect of guselkumab on general health state in biologic-naïve patients with active psoriatic arthritis through week 52 of the phase 3, randomized, placebo-controlled DISCOVER-2 trial. Adv Ther. 2022;39(10):4632-4644. DOI: org/10.1007/s12325-022-02269-0
  4. EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199-208. DOI: 1016/0168-8510(90)90421-9

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