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 was to assess the effect of MTX dose on clinical efficacy and safety in MTX-IR RA patients treated with filgotinib as add-on to background MTX for 24 weeks.
Methods:
Patients with active RA on stable dose of MTX were randomized in a double-blinded manner to receive either placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) as once or twice daily regimen for 24 weeks1. This post-hoc analysis includes patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO for the efficacy parameters, and all dose groups for the safety analysis. MTX dose was categorized as low (≤12.5mg/wk), medium (>12.5 to <17.5 mg/wk) or high (≥17.5mg/wk).
Results:
Baseline disease activity was high and similar across the three MTX subgroups, with an overall mean DAS28(CRP) score of 6.10, mean HAQ-DI of 1.73, mean CDAI score of 42.10 and mean SDAI score of 44.57. Across all MTX subgroups, patients on filgotinib 100mg or 200mg QD for 24 weeks showed efficacy over PBO, as measured by change from baseline in DAS28(CRP), CDAI, SDAI, HAQ-DI, and ACR20 response. No pattern was observed to suggest that the baseline MTX dose had any effect on filgotinib efficacy. The incidences of TEAE and serious TEAE were comparable regardless of the MTX dose (Table 2).
Conclusion:
Post-hoc analysis of a phase 2B study in MTX-IR RA patients suggests that filgotinib treatment at 100mg and 200mg QD on the background of MTX is consistently associated with improved clinical outcomes compared to placebo, across all key efficacy parameters, irrespective of MTX dose. The safety profile was overall favorable and consistent with previous studies in RA with filgotinib, regardless of MTX dose.
Table 1. Mean (SE) change from baseline in key efficacy parameters at Week 24 by MTX subgroup.
|
|
|
PBO |
filgotinib 100mg QD |
filgotinib 200mg QD |
|
|
|
Low MTX dose (≤12.5mg/wk) |
||||
|
|
N |
14 |
9 |
8 |
|
|
DAS28(CRP) |
-0.94 (0.28) |
-1.96 (0.47) |
-2.49 (0.43) |
||
|
CDAI |
-15.74 (4.67) |
-23.32 (6.36) |
-27.31 (5.27) |
||
|
SDAI |
-15.31 (4.68) |
-24.87 (6.34) |
-29.63 (5.70) |
||
|
HAQ-DI |
-0.30 (0.14) |
-0.61 (0.26) |
-0.73 (0.26) |
||
|
|
Medium MTX dose (>12.5 to <17.5mg/wk) |
||||
|
|
N |
43 |
48 |
44 |
|
|
|
DAS28(CRP) |
-1.05 (0.23) |
-2.77 (0.20) |
-2.73 (0.21) |
|
|
|
CDAI |
-14.49 (2.81) |
-29.73 (2.14) |
-30.05 (2.04) |
|
|
|
SDAI |
-14.35 (2.92) |
-31.49 (2.19) |
-31.30 (2.23) |
|
|
|
HAQ-DI |
-0.36 (0.11) |
-0.71 (0.09) |
-0.79 (0.08) |
|
|
|
High MTX dose (≥17.5mg/wk) |
||||
|
|
N |
28 |
27 |
34 |
|
|
|
DAS28(CRP) |
-1.51 (0.32) |
-2.82 (0.30) |
-2.97 (0.21) |
|
|
|
CDAI |
-18.67 (3.50) |
-28.47 (2.76) |
-29.18 (2.50) |
|
|
|
SDAI |
-18.36 (3.53) |
-29.48 (2.86) |
-30.95 (2.67) |
|
|
|
HAQ-DI |
-0.39 (0.10) |
-0.94 (0.15) |
-0.87 (0.13) |
|
|
|
ACR20 by subgroup, n (%) |
||||
|
|
Low MTX dose (≤12.5mg/wk) |
5 (36%) |
4 (44%) |
7 (88%) |
|
|
|
Medium MTX dose (>12.5 to <17.5mg/wk) |
18 (42%) |
31 (65%) |
32 (73%) |
|
|
|
High MTX dose (≥17.5mg/wk) |
13 (46%) |
17 (63%) |
24 (71%) |
|
Table 2. Treatment-emergent adverse events (TEAE) and serious TEAEs at Week 24 by MTX subgroup.
|
% of patients |
PBO
|
Filgotinib
|
|
Low MTX dose (≤12.5mg/wk) |
||
|
TEAE |
57 |
55 |
|
Serious TEAE |
7 |
3 |
|
Medium MTX dose (>12.5 to <17.5mg/wk) |
||
|
TEAE |
47 |
46 |
|
Serious TEAE |
2 |
2 |
|
High MTX dose (≥17.5mg/wk) |
||
|
TEAE |
57 |
57 |
|
Serious TEAE |
7 |
2 |
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:
Westhovens R, Van der Aa A, Jamoul C, Tasset C, Harrison P. Effect of Baseline MTX Dose on Clinical Efficacy and Safety in Rheumatoid Arthritis Patients Treated with Filgotinib: Post-Hoc Analysis from a Phase 2B Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effect-of-baseline-mtx-dose-on-clinical-efficacy-and-safety-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-a-phase-2b-study/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-baseline-mtx-dose-on-clinical-efficacy-and-safety-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-a-phase-2b-study/