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:
EXTEND (NCT01146652) is an ongoing open-label extension study enrolling patients completing five sarilumab originator studies (MOBILITY [NCT01061736]; TARGET [NCT01709578]; ASCERTAIN [NCT01768572]; ACT11575 [NCT01217814]; ONE [NCT02121210]) in adults with rheumatoid arthritis (RA). This analysis assessed safety and efficacy of sarilumab+csDMARDs after 4 years’ treatment.
Methods:
Patients received open-label sarilumab 200 mg q2w SC (reduced to 150 mg q2w if indicated). Primary outcome was treatment-emergent (TE) adverse events (AEs), and secondary outcomes comprised efficacy endpoints. This analysis included only patients receiving sarilumab+csDMARDs enrolling into EXTEND. Data are presented as observed.
Results:
Patients (mean age 52 years; 81% female) originally enrolled in MOBILITY (n=1283), TARGET (n=454), ASCERTAIN (n=168) and ACT11575 (n=7) were included. Median drug survival time was 312 weeks. At baseline, mean (range) duration of RA was 9.74 (0.3-54) years and 47.9% of patients had received prior bDMARDs. After 6007.1 patient-years’ follow-up, overall incidences of TEAEs, serious AEs and TEAEs leading to discontinuations were 186.0, 13.3, and 7.3 /100 patient-years, respectively. Infections were the most common AE of special interest (AESI; Table); incidences of serious infections and opportunistic infections were 3.7 and 0.9/100 patient-years, respectively. There were 24 deaths over the study period (11 due to infection). Incidences of AST/ALT>3x the upper limit of normal and Grade 3/4 neutropenia were 3.5%/8.6% and 10.4%/1.1%, respectively. Neutropenia was not associated with increased risk of infection. Confirmed GI perforations (0.1/100 patient-years) and thrombotic events were rare. Efficacy (DAS28‑CRP, CDAI, SDAI and HAQ-DI) was sustained over the study period (Figure). By Week 216, over 60% of continuing patients had achieved DAS28‑CRP <2.6. In patients switched to sarilumab 200 mg q2w from placebo or lower doses, efficacy quickly (over the first 12–24 weeks) reached that of sarilumab 200 mg q2w and was sustained.
Conclusion:
Through 4 years’ follow-up, the safety profile of sarilumab 200 mg q2w was consistent with anticipated class effects and no new safety signals were identified. The rate of serious infection remained consistent over the treatment period. Efficacy was sustained over time.
Acknowledgements
Study funding and medical writing support (Sarah Feeny, Adelphi Communications) provided by Sanofi and Regeneron Pharmaceuticals, Inc.
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Table. AE and AESI summary with sarilumab+csDMARDS in EXTEND (safety population) |
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MOBILITY |
TARGET |
ASCERTAIN |
ACT11575 |
Total |
|
|
Patient-years |
|
4480.6 |
1075.7 |
431.2 |
19.6 |
6007.1 |
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Safety overview, n (patients/100 patient-years)a |
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TEAEs |
7668 |
2520 |
949 |
37 |
11174 |
|
|
TE serious AEs |
572 (12.8) |
168 (15.6) |
57 (13.2) |
3 (15.3) |
800 (13.3) |
|
|
TEAEs leading to death |
21 (0.5) |
4 (0.4) |
3 (0.7) |
0 |
28 (0.5) |
|
|
TEAEs leading to discontinuation |
327 (7.3) |
82 (7.6) |
24 (5.6) |
4 (20.4) |
437 (7.3) |
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AESI, n (events/100 patient-years)b |
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|
|
|
|
|
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Infections |
2079 (46.4) |
615 (57.2) |
218 (50.6) |
11 (56.0) |
2923 (48.7) |
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Serious Infections |
169 (3.8) |
40 (3.7) |
10 (2.3) |
2 (10.2) |
221 (3.7) |
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Opportunistic infectionsc |
41 (0.9) |
11 (1.0) |
3 (0.7) |
1 (5.1) |
56 (0.9) |
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Herpes zosterc |
25 (0.6) |
13 (1.2) |
2 (0.5) |
1 (5.1) |
41 (0.7) |
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Tuberculosisc |
3 (0.1) |
1 (0.1) |
0 |
0 |
4 (0.1) |
|
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Leukopeniad |
584 (13.0) |
171 (15.9) |
81 (18.8) |
2 (10.2) |
838 (14.0) |
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Thrombocytopeniad |
61 (1.4) |
32 (3.0) |
9 (2.1) |
1 (5.1) |
103 (1.7) |
|
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Hepatic disorders |
327 (7.3) |
78 (7.3) |
26 (6.0) |
1 (5.1) |
432 (7.2) |
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Confirmed GI perforations |
10 (0.2) |
0 |
0 |
0 |
10 (0.2) |
|
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Elevation in lipidsd |
241 (5.4) |
66 (6.1) |
26 (6.0) |
0 |
333 (5.5) |
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Hypersensitivity |
159 (3.5) |
60 (5.6) |
18 (4.2) |
0 |
237 (3.9) |
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Anaphylaxis |
0 |
0 |
0 |
0 |
0 |
|
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Injection site reactions |
770 (17.2) |
234 (21.8) |
125 (29.0) |
0 |
1129 (18.8) |
|
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Malignancy |
23 (0.5) |
6 (0.6) |
6 (1.4) |
0 |
35 (0.6) |
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Malignancy excluding NMSC |
16 (0.4) |
3 (0.3) |
3 (0.7) |
0 |
22 (0.4) |
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Lupus-like syndrome |
3 (0.1) |
1 (0.1) |
0 |
0 |
4 (0.1) |
|
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Demyelinating disorders |
0 |
0 |
0 |
0 |
0 |
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GI, gastrointestinal; NMSC, non-melanoma skin cancer; aexposure period is cumulative time at risk of first event; bexposure period is cumulative total TEAE period; call cases of herpes zoster reported to date were localized; herpes zoster and tuberculosis were reported as opportunistic infections per protocol (not per clinical judgment); dindividual events were reported and laboratory abnormalities were not necessarily persistent. |
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To cite this abstract in AMA style:
Genovese MC, van Hoogstraten H, St. John G, Dong Q, Gómez-Reino JJ, Maldonado-Cocco JA, Carlos Salazar J, Huizinga TWJ, Burmester GR. Long-Term Treatment with Sarilumab Plus Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs): Pooled Safety and Efficacy with over 4 Years’ Treatment [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/long-term-treatment-with-sarilumab-plus-conventional-synthetic-disease-modifying-anti-rheumatic-drugs-csdmards-pooled-safety-and-efficacy-with-over-4-years-treatment/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-treatment-with-sarilumab-plus-conventional-synthetic-disease-modifying-anti-rheumatic-drugs-csdmards-pooled-safety-and-efficacy-with-over-4-years-treatment/