Session Information
Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has demonstrated safety and efficacy data in two 24-week placebo-controlled phase 2B studies as add-on to methotrexate and as monotherapy in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)1,2.
The objective is to evaluate the association between normalization of patient-reported outcome measures (PRO) and clinical response (ACR20) in MTX-IR RA patients treated with either filgotinib or placebo, as add-on to methotrexate (DARWIN 1), or as monotherapy (DARWIN 2).
Methods:
Patients with active RA were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (FIL, 50mg, 100mg or 200mg) as once daily (DARWIN 1 and DARWIN 2) or twice daily regimen (DARWIN 1) for 24 weeks .This post-hoc analysis at week 12 (W12) included patients treated FIL 100mg and 200mg QD (selected Phase 3 doses), and PBO. PRO included SF-36 (mental and physical components: MCS and PCS respectively; cut-off 50), FACIT-F (cut-off 40), and HAQ-DI (cut-off 0.5).
Results:
594 and 283 patients with active RA were randomized in DARWIN 1 and 2 respectively. In DARWIN 1, 44%, 64%, and 69% of patients on PBO, FIL 100mg QD and FIL 200mg QD respectively achieved ACR20 response at W12; in DARWIN 2 the respective response was 29%, 66%, and 72%. For all PRO parameters (SF-36 MCS, SF-36 PCS, FACIT-F and HAQ-DI) and in both studies, a higher proportion of patients with normalized scores was achieved in ACR20 responders compared to non-responders at W12 across treatment groups (Table 1). .
Conclusion:
This post-hoc analysis of two phase 2B studies in MTX-IR RA patients after 12 weeks of treatment suggests that normalization of PRO is associated with the ACR20 response, regardless of treatment with filgotinib and background MTX.
Table 1. Percentage of patients reaching normalized values for PRO at Week 12, by ACR20 response status.
|
% of patients |
Placebo |
100mg QD |
200mg QD |
|||
|
DARWIN 1 (MTX add-on), W12, ITT-LOCF |
||||||
|
|
ACR20 responders N=38 |
ACR20 non-responders N=48 |
ACR20 responders N=54 |
ACR20 non-responders N=31 |
ACR20 responders N=59 |
ACR20 non-responders N=27 |
|
SF-36 MCS ≥50 |
52.6 |
27.1 |
59.3 |
35.5 |
59.3 |
33.3 |
|
SF-36 PCS ≥50 |
7.9 |
0 |
14.8 |
0 |
16.9 |
0 |
|
FACIT-F ≥40 |
39.5 |
10.4 |
57.4 |
25.8 |
50.8 |
25.9 |
|
HAQ-DI ≤0.5 |
23.7 |
0 |
31.5 |
19.4 |
40.7 |
7.4 |
|
DARWIN 2 (monotherapy), W12, ITT-LOCF |
||||||
|
|
ACR20 responders N=21 |
ACR20 non-responders N=51 |
ACR20 responders N=46 |
ACR20 non-responders N=24 |
ACR20 responders N=50 |
ACR20 non-responders N=19 |
|
SF-36 MCS ≥50 |
42.9 |
23.5 |
54.3 |
33.3 |
52.0 |
47.4 |
|
SF-36 PCS ≥50 |
9.5 |
2.0 |
17.4 |
4.2 |
14.0 |
10.5 |
|
FACIT-F ≥40 |
38.1 |
7.8 |
52.2 |
8.3 |
42.0 |
36.8 |
|
HAQ-DI ≤0.5 |
19.0 |
0 |
32.6 |
4.2 |
30.0 |
21.1 |
References
1Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.
To cite this abstract in AMA style:
Genovese MC, Van der Aa A, Jamoul C, Tasset C, Harrison P, Westhovens R, Kavanaugh A. Association between Clinical Response and Normalization of Patient-Reported Outcome Measures in Rheumatoid Arthritis: Post-Hoc Analysis from Two Phase 2b Filgotinib Studies [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/association-between-clinical-response-and-normalization-of-patient-reported-outcome-measures-in-rheumatoid-arthritis-post-hoc-analysis-from-two-phase-2b-filgotinib-studies/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-clinical-response-and-normalization-of-patient-reported-outcome-measures-in-rheumatoid-arthritis-post-hoc-analysis-from-two-phase-2b-filgotinib-studies/