Search
Close
Search
Advanced Search
Search Menu

Background: Filgotinib, an oral, selective JAK1-inhibitor, showed sustained improvements of signs and symptoms in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) in two 24-week Phase 2B studies, with acceptable safety profile. The objective was to investigate speed of onset of effect of filgotinib based on clinical and patient-reported outcome (PRO) measures in DARWIN 1 (MTX add-on).

Methods: Patients with active RA were randomized in a double-blind manner to placebo (PBO) or one of three total daily doses of filgotinib (50mg, 100mg, 200mg) and two regimens (qd and bid) for 24 weeks. Assessed clinical measures included ACR20, ACR50 and DAS28-(CRP). PROs were patient’s evaluation of disease activity and pain, physical function, fatigue and HRQoL-SF36. This presentation reports results from patients dosed with filgotinib 100mg or 200mg qd (selected Phase 3 doses) or PBO.

Results: 594 patients were randomized and dosed. Baseline mean DAS28-(CRP) was 6.1 and mean HAQ-DI was 1.7, indicating significant impairment. Rapid onset of efficacy was observed with filgotinib 100mg and 200mg, with significant differences from PBO as of week 1 for ACR20, DAS28-(CRP) and serum CRP concentrations. Filgotinib introduced rapid and statistically significant improvement in PROs with both doses: 200mg qd showed statistically significant effects as early as week 1 for patient global disease activity, week 2 for patient pain and HAQ-DI and week 4 (earliest timepoint measured) for FACIT and SF-36 PCS. With 100mg qd, patient global disease activity, patient pain and HAQ-DI significantly improved from week 2, FACIT and SF-36 (PCS and MCS) as of week 4 (Table 1). Responses were maintained or continued to improve throughout 24 weeks treatment.

Conclusion: Filgotinib 100mg and 200mg qd as add-on treatment to MTX, led to early onset of efficacy as of week 1 and to rapid decrease in RA disease burden as demonstrated by significant improvement in PROs as of the first timepoint measured.

Disclosure statement: P.C.T.: Consultancies: Eli Lilly, Pfizer, Janssen, GlaxoSmithKline, Novartis, Celgene, AbbVie, Biogen, Sandoz, Bristol-Myers Squibb, UCB. Grants/research support: Galapagos, Celgene, GlaxoSmithKline, UCB, Janssen. R.W.: Consultancies: GSI. Member of speakersण128;™ bureau: Bristol-Myers Squibb. Grants/research support: Roche. Other: DARWIN 1 PI for Galapagos. V.V.: Other: Galapagos employee. L.M.: Other: Galapagos employee. A.V.der A.: Other: Galapagos employee. P.H.: Other; Galapagos employee. C.T.: Other: Galapagos employee.

O02 Table 1.

Clinical and PRO responses for the PBO, 100 and 200 mg/day qd dose groups

Placebo (n = 86)100 mg/day (n = 85)200 mg/day (n = 86)
ACR20 (% of subjects, NRI)W118.634.1*27.9
W227.945.9*48.8**
W438.451.8+54.7*
ACR50 (% of subjects, NRI)W11.24.74.7
W25.820.0**10.5
W47.032.9***17.4*
DAS28-(CRP) (mean CFB, LOCF)W1−0.6−1.0**−1.2***
W2−0.8−1.5***−1.5***
W4−1.0−1.9***−1.9***
CDAI (mean CFB, LOCF)W1−8.5−11.1−11.1
W2−11.6−17.3**−14.6
W4−13.3−21.4***−20.4***
CRP (mg/L) (mean CFB, LOCF)W11.8−11.0***−17.1***
W21.6−12.9***−17.5***
W42.3−13.2***−17.9***
SF-36 PCS (mean CFB, LOCF)W43.06.1*6.4**
SF-36 MCS (mean CFB, LOCF)W43.04.9*5.4+
FACIT-Fatigue (mean CFB, LOCF)W44.99.1**8.5*
HAQ-DI (mean CFB, LOCF)W1−0.20−0.32+−0.27
W2−0.23−0.41*−0.45**
W4−0.34−0.52*−0.55*
Patient Global Disease Activity VAS (mean CFB, LOCF)W1−8.9−12.9−16.7*
W2−10.6−20.9*−21.8**
W4−13.2−24.4**−24.9*
Patient Pain VAS (mean CFB, LOCF)W1−8.2−12.6−12.2
W2−12.2−18.9*−22.2**
W413.9−23.5**−25.4**
Placebo (n = 86)100 mg/day (n = 85)200 mg/day (n = 86)
ACR20 (% of subjects, NRI)W118.634.1*27.9
W227.945.9*48.8**
W438.451.8+54.7*
ACR50 (% of subjects, NRI)W11.24.74.7
W25.820.0**10.5
W47.032.9***17.4*
DAS28-(CRP) (mean CFB, LOCF)W1−0.6−1.0**−1.2***
W2−0.8−1.5***−1.5***
W4−1.0−1.9***−1.9***
CDAI (mean CFB, LOCF)W1−8.5−11.1−11.1
W2−11.6−17.3**−14.6
W4−13.3−21.4***−20.4***
CRP (mg/L) (mean CFB, LOCF)W11.8−11.0***−17.1***
W21.6−12.9***−17.5***
W42.3−13.2***−17.9***
SF-36 PCS (mean CFB, LOCF)W43.06.1*6.4**
SF-36 MCS (mean CFB, LOCF)W43.04.9*5.4+
FACIT-Fatigue (mean CFB, LOCF)W44.99.1**8.5*
HAQ-DI (mean CFB, LOCF)W1−0.20−0.32+−0.27
W2−0.23−0.41*−0.45**
W4−0.34−0.52*−0.55*
Patient Global Disease Activity VAS (mean CFB, LOCF)W1−8.9−12.9−16.7*
W2−10.6−20.9*−21.8**
W4−13.2−24.4**−24.9*
Patient Pain VAS (mean CFB, LOCF)W1−8.2−12.6−12.2
W2−12.2−18.9*−22.2**
W413.9−23.5**−25.4**

P-values, uncorrected for multiplicityy: +P < 0.10,

*

P < 0.05;

**

P < 0.01;

***

P < 0.001 vs PBO.

CFB, change from baseline; LOCF, last observation carried forward; NRI, non-responder imputation; VAS, visual analogue scale.

Open in new tab
O02 Table 1.

Clinical and PRO responses for the PBO, 100 and 200 mg/day qd dose groups

Placebo (n = 86)100 mg/day (n = 85)200 mg/day (n = 86)
ACR20 (% of subjects, NRI)W118.634.1*27.9
W227.945.9*48.8**
W438.451.8+54.7*
ACR50 (% of subjects, NRI)W11.24.74.7
W25.820.0**10.5
W47.032.9***17.4*
DAS28-(CRP) (mean CFB, LOCF)W1−0.6−1.0**−1.2***
W2−0.8−1.5***−1.5***
W4−1.0−1.9***−1.9***
CDAI (mean CFB, LOCF)W1−8.5−11.1−11.1
W2−11.6−17.3**−14.6
W4−13.3−21.4***−20.4***
CRP (mg/L) (mean CFB, LOCF)W11.8−11.0***−17.1***
W21.6−12.9***−17.5***
W42.3−13.2***−17.9***
SF-36 PCS (mean CFB, LOCF)W43.06.1*6.4**
SF-36 MCS (mean CFB, LOCF)W43.04.9*5.4+
FACIT-Fatigue (mean CFB, LOCF)W44.99.1**8.5*
HAQ-DI (mean CFB, LOCF)W1−0.20−0.32+−0.27
W2−0.23−0.41*−0.45**
W4−0.34−0.52*−0.55*
Patient Global Disease Activity VAS (mean CFB, LOCF)W1−8.9−12.9−16.7*
W2−10.6−20.9*−21.8**
W4−13.2−24.4**−24.9*
Patient Pain VAS (mean CFB, LOCF)W1−8.2−12.6−12.2
W2−12.2−18.9*−22.2**
W413.9−23.5**−25.4**
Placebo (n = 86)100 mg/day (n = 85)200 mg/day (n = 86)
ACR20 (% of subjects, NRI)W118.634.1*27.9
W227.945.9*48.8**
W438.451.8+54.7*
ACR50 (% of subjects, NRI)W11.24.74.7
W25.820.0**10.5
W47.032.9***17.4*
DAS28-(CRP) (mean CFB, LOCF)W1−0.6−1.0**−1.2***
W2−0.8−1.5***−1.5***
W4−1.0−1.9***−1.9***
CDAI (mean CFB, LOCF)W1−8.5−11.1−11.1
W2−11.6−17.3**−14.6
W4−13.3−21.4***−20.4***
CRP (mg/L) (mean CFB, LOCF)W11.8−11.0***−17.1***
W21.6−12.9***−17.5***
W42.3−13.2***−17.9***
SF-36 PCS (mean CFB, LOCF)W43.06.1*6.4**
SF-36 MCS (mean CFB, LOCF)W43.04.9*5.4+
FACIT-Fatigue (mean CFB, LOCF)W44.99.1**8.5*
HAQ-DI (mean CFB, LOCF)W1−0.20−0.32+−0.27
W2−0.23−0.41*−0.45**
W4−0.34−0.52*−0.55*
Patient Global Disease Activity VAS (mean CFB, LOCF)W1−8.9−12.9−16.7*
W2−10.6−20.9*−21.8**
W4−13.2−24.4**−24.9*
Patient Pain VAS (mean CFB, LOCF)W1−8.2−12.6−12.2
W2−12.2−18.9*−22.2**
W413.9−23.5**−25.4**

P-values, uncorrected for multiplicityy: +P < 0.10,

*

P < 0.05;

**

P < 0.01;

***

P < 0.001 vs PBO.

CFB, change from baseline; LOCF, last observation carried forward; NRI, non-responder imputation; VAS, visual analogue scale.

Open in new tab

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Topic:
Issue Section:
ORAL PRESENTATIONS (Tuesday 25 April 2017)
Download all slides

Comments

0 Comments
Comments (0)
Submit a comment
You have entered an invalid code
Thank you for submitting a comment on this article. Your comment will be reviewed and published at the journal's discretion. Please check for further notifications by email.