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 evaluate the effect of baseline serum CRP levels on clinical efficacy after 12 weeks of treatment, as assessed by the ACR and DAS28(CRP) subcomponents in MTX-IR RA patients treated with filgotinib.
Methods:
Patients were randomized in a double-blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) for 24 weeks. In the DARWIN 1 study, filgotinib on MTX background was evaluated as once (QD) or twice daily treatment. In the DARWIN 2 study once-daily filgotinib was assessed as monotherapy. The inclusion criterion for CRP was amended during the studies and was decreased from 13.5 mg/L to 6.3 mg/L. This post-hoc analysis included patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO. Efficacy outcomes were analyzed by baseline CRP level (low: ≤9 mg/L and high: >9 mg/L, with 9mg/L as ULN).
Results:
Baseline disease activity was high and balanced across the different treatment groups. Comparable baseline values were shown between both CRP subgroups, except for the mean CRP levels (Table 1).
In both low and high CRP subgroups, patients on filgotinib at 100mg or 200mg QD for 12 weeks showed efficacy over PBO, as measured by change from baseline in different subcomponents of the ACR/DAS28(CRP) composite score (TJC68, SJC66, Pt pain, Pt GDA, Inv GDA, HAQ-DI and CRP) (Table 1). In both studies, there was no clear pattern suggesting that baseline CRP level had a consistent effect on filgotinib efficacy.
Conclusion:
This post-hoc analysis of two Phase 2B studies in MTX-IR RA patients suggests that filgotinib treatment once daily at 100mg and 200mg both on the background of MTX and as monotherapy was consistently associated with improved clinical outcomes compared to placebo at Week 12, regardless of baseline CRP levels, as measured by ACR and DAS28(CRP) subcomponents.
Table 1. Mean baseline and change from baseline (SE) values in key efficacy parameters at Week 12 by CRP subgroup
|
|
DARWIN 1 |
DARWIN 2 |
||||||||
|
|
PBO
|
filgotinib 100mg QD |
filgotinib 200mg QD |
PBO |
filgotinib 100mg QD |
filgotinib 200mg QD |
||||
|
Low CRP subgroup (≤9 mg/L) |
||||||||||
|
N |
33 |
25 |
15 |
11 |
20 |
20 |
||||
|
TJC68 |
23.45 -9.42 (2.68) |
21.94 -12.17 (2.04) |
26.60 -14.87 (2.82) |
21.64 -3.55 (3.59) |
27.13 -14.68 (2.90) |
23.70 -16.63 (2.71) |
||||
|
SJC66 |
15.52 -8.82 (1.62) |
14.30 -10.09 (1.57) |
17.00 -12.07 (2.53) |
14.18 -5.09 (3.11) |
19.50 -10.75 (2.04) |
13.21 -9.51 (1.30) |
||||
|
Pt pain |
64.94 -19.24 (6.41) |
61.24 -30.12 (5.77) |
69.67 -27.27 (6.25) |
72.64 -11.27 (7.63) |
73.15 -36.05 (6.76) |
66.05 -32.30 (8.50) |
||||
|
Pt GDA |
62.88 -17.82 (5.92) |
66.96 -36.16 (5.74) |
72.60 -35.33 (7.88) |
74.09 -13.36 (7.68) |
71.85 -38.20 (5.74) |
67.80 -30.25 (7.35) |
||||
|
Inv GDA |
65.27 -29.24 (5.84) |
65.84 -38.88 (4.85) |
67.00 -41.40 (5.53) |
76.18 -33.36 (9.51) |
74.25 -50.50 (4.73) |
68.55 -49.75 (4.86) |
||||
|
HAQ-DI |
1.47 -0.21 (0.121) |
1.51 -0.76 (0.133) |
1.91 -0.64 (0.100) |
1.93 -0.12 (0.163) |
1.75 -0.74 (0.172) |
1.72 -0.74 (0.158) |
||||
|
CRP |
5.57 +5.97 (2.53) |
5.57 +0.14 (1.96) |
4.29 +0.04 (1.69) |
4.44 +1.56 (1.49) |
5.20 -0.09 (0.99) |
4.41 +0.89 (1.31) |
||||
|
High CRP subgroup (>9 mg/L) |
||||||||||
|
N |
53 |
60 |
71 |
61 |
50 |
49 |
||||
|
TJC68 |
25.94 -8.98 (1.44) |
26.73 -14.86 (1.68) |
29.32 -18.22 (1.49) |
25.87 -6.21 (1.62) |
27.22 -15.29 (1.82) |
27.28 -17.73 (1.79) |
||||
|
SJC66 |
16.51 -6.87 (1.03) |
17.15 -9.67 (1.22) |
17.43 -10.80 (1.03) |
16.30 -3.89 (1.34) |
18.31 -11.65 (1.48) |
16.77 -10.87 (1.27) |
||||
|
Pt pain |
66.11 -15.49 (3.53) |
67.14 -26.19 (3.72) |
66.42 -32.24 (3.29) |
71.38 -13.70 (3.41) |
72.42 -29.66 (4.02) |
69.00 -30.86 (3.82) |
||||
|
Pt GDA |
65.00 -15.98 (3.39) |
67.83 -26.18 (3.84) |
67.87 -33.94 (3.46) |
70.59 -11.21 (3.19) |
71.30 -26.78 (4.03) |
69.33 -27.43 (3.57) |
||||
|
Inv GDA |
67.25 -25.77 (3.65) |
66.65 -31.33 (3.10) |
65.54 -37.25 (2.62) |
69.33 -21.87 (3.29) |
71.14 -39.02 (3.15) |
67.33 -38.38 (3.30) |
||||
|
HAQ-DI |
1.83 -0.49 (0.080) |
1.78 -0.61 (0.087) |
1.73 -0.78 (0.076) |
1.77 -0.25 (0.074) |
1.82 -0.65 (0.081) |
1.82 -0.74 (0.086) |
||||
|
CRP |
22.89 +0.61 (3.22) |
32.44 -19.28 (3.60) |
31.91 -20.90 (3.88) |
40.82 -10.56 (5.01) |
33.70 -17.12 (6.19) |
30.82 -21.27 (3.33) |
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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:
Kavanaugh A, Van der Aa A, Jamoul C, Tasset C, Harrison P, Westhovens R. No Effect of Baseline Serum CRP Levels on Clinical Efficacy Parameters in Rheumatoid Arthritis Patients Treated with Filgotinib: Post Hoc Analysis from Two Phase 2B Studies [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/no-effect-of-baseline-serum-crp-levels-on-clinical-efficacy-parameters-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-two-phase-2b-studies/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/no-effect-of-baseline-serum-crp-levels-on-clinical-efficacy-parameters-in-rheumatoid-arthritis-patients-treated-with-filgotinib-post-hoc-analysis-from-two-phase-2b-studies/