Session Information
Date: Tuesday, October 23, 2018
Title: Rheumatoid Arthritis – Treatments Poster III: Biosimilars and New Compounds
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
The orally administered, selective inhibitor of Janus Kinase 1 (JAK1), filgotinib (FIL), is currently being investigated for the treatment of rheumatoid arthritis (RA) in Phase 3 studies and in other inflammatory diseases.
The long-term safety and efficacy of FIL in patients (pts) with RA is being evaluated in the DARWIN 3 (Phase 2b) open-label extension (OLE).
Methods:
Two 24-week Phase 2b studies, DARWIN 1 and 2 (Ref 1, 2) evaluated the safety and efficacy of FIL in pts with moderately to severely active RA. Eligible pts from these studies could enroll in DARWIN 3. In this OLE study, pts received FIL 200 mg QD or 100 mg BID or 100 mg QD (US males only). Here we present cumulative safety data (from the first dose of FIL in the DARWIN program through 20 Feb 2018) and efficacy data (from DARWIN 3 Day 1 to Week 132).
Results:
Of 877 pts from DARWIN 1 and 2, 790 (90%) completed the study, and 739 (84%) enrolled in DARWIN 3; 603 (82%) were female, mean age was 53 years. At analysis, 469/739 (64%) remained in the OLE. Cumulative patient years of exposure (PYE) was 2081, median time on study drug was 1197 days. Key safety data are summarized in Table 1; laboratory abnormalities are shown in Table 2. No new trends or safety signals were identified. Efficacy data revealed that 89%, 70%, and 49% of pts had ACR20/50/70 responses, respectively, and 69% achieved DAS28-CRP ≤3.2 (observed case analysis).
Conclusion:
Filgotinib continues to demonstrate a favorable safety and tolerability profile in pts with RA over a 2.5-year period, with maintenance of therapeutic response in the long-term.
Table 1: Key Safety Events Per 100 PYE
|
Filgotinib (200mg daily) + MTX |
Filgotinib (200mg daily) Monotherapy |
Total* |
|
|
PYE=1443 |
PYE=599 |
PYE=2042 |
|
|
Treatment-emergent AEs (TEAEs) |
144.1 |
151.5 |
146.3 |
|
Serious TEAEs |
5.1 |
6.8 |
5.6 |
|
TEAEs for Infections |
41.6 |
36 |
40 |
|
Serious TEAEs for Infections |
0.8 |
1.7 |
1 |
|
Malignancy (excluding NMSC†) |
0.6 |
0.7 |
0.6 |
|
Herpes Zoster |
1.5 |
1.5 |
1.5 |
|
Deep Vein Thrombosis ‡ |
0.07 |
0 |
0.05 |
|
Pulmonary Embolism‡ |
0.07 |
0 |
0.05 |
|
Active Tuberculosis |
0 |
0 |
0 |
|
Deaths |
0.1 |
0.5 |
0.2 |
* Treatment groups with fewer than 10 subjects were omitted for clarity; †Non-melanoma skin cancer;
‡Single patient DVT leading to PE.
Table 2. Key Treatment-Emergent Laboratory Abnormalities
|
Filgotinib (200mg daily) + MTX |
Filgotinib (200mg daily) Monotherapy |
Total* |
|
|
N=500† |
N=224 |
N=724 |
|
|
Grade 1 or 2 (% of patients‡) |
|||
|
Hemoglobin Decrease |
22.8% |
28.6% |
24.6% |
|
Lymphocytes Decrease |
21.6% |
16.1% |
19.9% |
|
Neutrophils Decrease |
11.0% |
12.5% |
11.5% |
|
Platelets Decrease |
3.8% |
2.2% |
3.3% |
|
ALT Increase |
26.5% |
18.8% |
24.1% |
|
Creatinine Increase |
3.8% |
8.0% |
5.1% |
|
Grade 3 or 4 (% of patients‡) |
|||
|
Hemoglobin Decrease |
1.0% |
0.9% |
1.0% |
|
Lymphocytes Decrease |
3.6% |
1.8% |
3.1% |
|
Neutrophils Decrease |
1.0% |
1.3% |
1.1% |
|
Platelets Decrease |
0.4% |
0 |
0.2% |
|
ALT Increase |
0.4% |
0.9% |
0.6% |
|
Creatinine Increase |
0.2% |
0 |
0.1% |
*Treatment groups with fewer than 10 subjects were omitted for clarity; †One patient in this group did not have post-baseline data due to withdrawal from the study; ‡Percent of patients who had at least one measured laboratory parameter of the listed grades.
References
- Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2. Kavanaugh A, et al. Ann Rheum Dis 2017;76:1009-1019.
To cite this abstract in AMA style:
Kavanaugh A, Genovese MC, Winthrop K, Greenwald M, Ponce L, Enriquez Sosa F, Stanislavchuk M, Mazur M, Spindler A, Cseuz R, Nikulenkova N, Glowacka-Kulesz M, Szombati I, Dudek A, Mozaffarian N, Greer J, Kunder R, An D, Meuleners L, Besuyen R, Alten R, Westhovens R. Rheumatoid Arthritis Treatment with Filgotinib: Week 132 Safety Data from a Phase 2b Open-Label Extension Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/rheumatoid-arthritis-treatment-with-filgotinib-week-132-safety-data-from-a-phase-2b-open-label-extension-study/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-arthritis-treatment-with-filgotinib-week-132-safety-data-from-a-phase-2b-open-label-extension-study/