Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose Interleukin-6 (IL-6) regulates a diverse array of activities that may underlie systemic and local symptoms of rheumatoid arthritis (RA). The efficacy of sarilumab, a fully human monoclonal antibody (mAb) directed against IL-6R, has recently been investigated in the randomized, double-blind, placebo(pbo)-controlled, multicenter, phase 3 part of the MOBILITY study.1 This analysis expands the profile to the entire 52-week duration of the trial.
Methods Adults with active, moderate-to-severe RA and inadequate response to methotrexate (MTX) were randomized 1:1:1 to pbo + MTX, sarilumab 150 mg or 200 mg q2w + MTX for 52 wks. 3 co-primary endpoints associated with RA activity (signs & symptoms, physical function, and structural damage) were investigated: proportion of patients achieving ACR20 response at Wk 24; change from baseline in HAQ-DI at Wk 16; and change from baseline in mTSS at Wk 52. Secondary efficacy endpoints included major clinical response at Wk 52, ACR50 and ACR70 responses, reduction in DAS28-CRP, and CDAI.
Results Sarilumab 150 mg and 200 mg q2w + MTX provided statistically significant, clinically meaningful improvement in all co-primary efficacy endpoints (ACR20, HAQ-DI, and mTSS) and secondary efficacy endpoints vs pbo + MTX (Table). ACR 20 response rates increased by Wk 2 and remained significantly higher in both sarilumab + MTX groups vs pbo + MTX through Wk 52 (p<0.0001). Change from baseline in the ACR core set of disease activity measures, swollen and tender joint counts, was significantly higher in the sarilumab + MTX groups vs pbo + MTX (Table). A significantly higher proportion of patients in the sarilumab + MTX groups maintained CDAI remission vs pbo + MTX (Wks 4–52; p<0.0001). DAS28-CRP scores were significantly improved vs pbo + MTX at Wks 2–52 (p<0.0001) in sarilumab + MTX-treated patients, who achieved DAS28-CRP remission at Wks 24 and 52 (Table). The proportion of HAQ-DI responders at Wks 16, 24 and 52 was significantly higher (p<0.0001) with sarilumab + MTX vs pbo + MTX at each timepoint (Table). Mean change from baseline in mTSS at Wk 52 with sarilumab + MTX was significantly higher vs pbo + MTX (Table). Most common TEAEs included infections and injection site reactions. A higher incidence of serious infections was observed with sarilumab. Lab abnormalities included decreases in neutrophils and increases in transaminases and lipids.
Conclusion These additional analyses of patients with active RA and an inadequate response to MTX showed that treatment with subcutaneous sarilumab at 150 mg and 200 mg q2w + MTX improved the full range of reported outcomes in a robust and durable manner that was maintained over this 52 week-trial.
Reference: 1. Genovese M et al. Abstr. No. EULAR14-SCIE-3001 presented at EULAR 2014, Paris, France.
|
Table. Efficacy results |
|
Sarilumab |
|
|
Placebo + MTX (n=398) |
150 mg q2w + MTX (n=400) |
200 mg q2w + MTX (n=399) |
|
|
ACR20 response – Wk 24, n (%) |
133 (33.4%) |
232 (58.0%)* |
265 (66.4%)* |
|
ACR50 response – Wk 24, n (%) |
66 (16.6%) |
148 (37.0%)* |
182 (45.6%)* |
|
ACR70 response – Wk 24, n (%) |
29 (7.3%) |
79 (19.8%)* |
99 (24.8%)* |
|
mTSS, mean change from BL – Wk 52 |
2.8 |
0.9* |
0.3* |
|
Major clinical response (ACR70 response maintained for 24 weeks), n (%) |
12 (3.0%) |
51 (12.8%)* |
59 (14.8%)* |
|
ACR disease activity measures, adj. mean change from BL – Wk 24 |
|
|
|
|
Swollen joint count |
–6.6 |
–10.6* |
–11.2* |
|
Tender joint count |
–10.1 |
–16.9* |
–17.4* |
|
HAQ-DI, adj. mean change from BL – – Wk 16 |
–0.3 |
–0.5* |
–0.6* |
|
– Wk 24 |
–0.4 |
–0.6* |
–0.6* |
|
– Wk 52 |
–0.5 |
–0.7* |
–0.8* |
|
DAS28–CRP |
|
|
|
|
LS mean change from BL – Wk 24 |
–1.17 |
–2.45* |
–2.82* |
|
LS mean change from BL – Wk 52 |
–1.36 |
–2.78* |
–2.95* |
|
Clinical remission# – Wk 24, n (%) |
40 (10.1%) |
111 (27.8%)* |
136 (34.1%)* |
|
Clinical remission# – Wk 52, n (%) |
34 (8.5%) |
124 (31.0%)* |
136 (34.1%)* |
|
CDAI |
|
|
|
|
LS mean change from BL – Wk 24 |
–14.47 |
–23.89* |
25.79* |
|
LS mean change from BL – Wk 52 |
–17.50 |
–26.96* |
–27.26* |
|
Remission (≤2.8) – Wk 24, n (%) |
20 (5.0%) |
41 (10.3%)† |
55 (13.8%)* |
|
Remission (≤2.8) – Wk 52, n (%) |
19 (4.8%) |
59 (14.8%)* |
72 (18.0%)* |
|
No radiographic progression at Wk 52, n (%) |
154 (38.7%) |
191 (47.8%)‡ |
222 (55.6%)* |
|
*p<0.0001 vs placebo + MTX; †p=0.0053; ‡p<0.01 vs placebo + MTX; #score of <2.6; MTX, methotrexate; BL, baseline; LS, least squared; ACR 20/50/70, American College of Rheumatology 20%/50%/70% improvement criteria; mTSS, van der Heijde modified total Sharp score; HAQ-DI, Health Assessment Questionnaire-Disability Index; HAQ-DI responders, >0.3 improvement in HAQ-DI from baseline; DAS28-CRP, Disease Activity Score in 28 joints using C-Reactive Protein; DAS28-CRP remission, DAS28-CRP <2.6; CDAI, Clinical Disease Activity Index; CDAI remission, CDAI ≤2.8. |
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Disclosure:
A. Kavanaugh,
Sanofi ,
2;
D. L. Decktor,
Regeneron Pharmaceuticals, Inc.,
3,
Johnson & Johnson,
1;
C. Fan,
Sanofi ,
1,
Sanofi ,
3;
J. van Adelsberg,
Regeneron Pharmaceuticals, Inc.,
3,
Regeneron Pharmaceuticals, Inc.,
1;
R. Martincova,
Sanofi ,
3;
M. C. Genovese,
Eli Lilly and Company,
2,
Eli Lilly and Company,
5,
Sanofi ,
2,
Sanofi ,
5,
Regeneron,
2,
Regeneron,
5.
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