Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Sarilumab, a fully human monoclonal antibody directed against the IL-6 receptor, demonstrated efficacy in the phase 3 part of the RA-MOBILITY study (NCT01061736) in adults with active, moderate-to-severe RA with inadequate responses to methotrexate (MTX).1 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. This analysis focuses on the impact of sarilumab + MTX on HRQoL, fatigue, and sleep, all of which were pre-defined secondary endpoints at Week 24 among patients who had a patient reported outcome (PRO) measured at that time point. Overall work impairment due to RA was assessed at Week 12.
Methods: The intent-to-treat population included 1,197 patients who were randomized 1:1:1 to receive placebo + MTX, sarilumab 150 mg every two weeks (q2w) + MTX or 200 mg q2w + MTX. The Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Sleep-Visual Analog Scale (Sleep-VAS) and Work Productivity and Activity Impairment (WPAI) questionnaires were assessed at baseline, Weeks 12 (WPAI only), 24 and 52.
Results: Statistically significant improvements versus placebo + MTX in SF-36 T-Scores for Physical Component Summary (PCS) and Mental Component Summary (MCS), all 8 domains of SF-36, FACIT-F and Sleep-VAS were reported by patients receiving sarilumab 150 mg + MTX and 200 mg + MTX at Week 24, which exceeded the minimum clinically important difference (MCID) in all SF-36 summary and domain scores (PCS and MCS: 2.5; 8 domains: 5.0), FACIT-F (3.0) and Sleep-VAS (4.1) scores in both active treatment groups (Table 1, Bolded). Improvements evident at Week 24 were sustained through Week 52. Statistically significant improvements in WPAI “% overall work impairment due to RA” scores were reported for 150 mg + MTX group at Week 12.
Conclusion: In this Phase 3 trial, patients with active RA receiving either dose of sarilumab q2w + MTX reported clinically meaningful change from baseline in all HRQoL and fatigue scores at Week 24, which were maintained through Week 52. Statistically significant benefit was also reported in sleep and “% overall work impairment due to RA” for sarilumab 150 mg q2w + MTX dose.
1. Genovese M et al. Abstr. EULAR14-SCIE-3001, EULAR 2014.
Table 1. HRQoL, Fatigue, WPAI-% overall work impairment due to RA, and Sleep-VAS at Baseline, Week 12 (for WPAI only), and Week 24
|
PRO |
Placebo |
Sarilumab 150 mg + MTX |
Sarilumab 200 mg + MTX |
|
SF-36 PCS |
|||
|
Baseline mean |
32.15 |
31.92 |
31.24 |
|
Mean change from baseline |
5.27 |
8.16 |
8.83 |
|
LSM difference, 95% CI |
2.860(1.630,4.091) |
3.201(1.978,4.423) |
|
|
p-value |
<0.0001 |
<0.0001 |
|
|
SF-36 MCS |
|||
|
Baseline mean |
37.82 |
39.46 |
38.92 |
|
Mean change from baseline |
3.98 |
5.10 |
7.79 |
|
LSM difference, 95% CI |
1.808(0.285,3.331) |
4.271(2.761,5.781) |
|
|
p-value |
0.0200 |
<0.0001 |
|
|
SF-36 PF |
|||
|
Baseline mean |
29.06 |
29.36 |
28.70 |
|
Mean change from baseline |
4.97 |
7.19 |
7.77 |
|
LSM difference, 95% CI |
2.357(0.809,3.906) |
2.650(1.106,4.194) |
|
|
p-value |
0.0029 |
0.0008 |
|
|
SF-36 RP |
|||
|
Baseline mean |
31.93 |
32.37 |
32.03 |
|
Mean change from baseline |
4.99 |
7.10 |
7.92 |
|
LSM difference, 95% CI |
2.324(0.952,3.696) |
2.991(1.628,4.354) |
|
|
p-value |
0.0009 |
<0.0001 |
|
|
SF-36 BP |
|||
|
Baseline mean |
33.13 |
33.20 |
32.65 |
|
Mean change from baseline |
6.59 |
10.75 |
12.02 |
|
LSM difference, 95% CI |
4.256(2.864,5.649) |
5.193(3.807,6.580) |
|
|
p-value |
<0.0001 |
<0.0001 |
|
|
SF-36 GH |
|||
|
Baseline mean |
35.04 |
35.41 |
34.13 |
|
Mean change from baseline |
3.83 |
6.11 |
7.73 |
|
LSM difference, 95% CI |
2.473(1.179,3.767) |
3.597(2.312,4.881) |
|
|
p-value |
0.0002 |
<0.0001 |
|
|
SF-36 VT |
|||
|
Baseline mean |
40.67 |
41.30 |
40.19 |
|
Mean change from baseline |
5.43 |
7.16 |
9.72 |
|
LSM difference, 95% CI |
2.073(0.580,3.566) |
4.127(2.647,5.607) |
|
|
p-value |
0.0066 |
<0.0001 |
|
|
SF-36 SF |
|||
|
Baseline mean |
34.38 |
35.59 |
34.76 |
|
Mean change from baseline |
4.50 |
7.11 |
9.12 |
|
LSM difference, 95% CI |
3.270(1.786,4.754) |
4.814(3.340,6.288) |
|
|
p-value |
<0.0001 |
<0.0001 |
|
|
SF-36 RE |
|||
|
Baseline mean |
30.70 |
31.41 |
31.49 |
|
Mean change from baseline |
4.50 |
6.21 |
7.70 |
|
LSM difference, 95% CI |
1.997(0.236,3.759) |
3.548(1.800,5.297) |
|
|
p-value |
0.0263 |
<0.0001 |
|
|
SF-36 MH |
|||
|
Baseline mean |
37.07 |
39.15 |
37.59 |
|
Mean change from baseline |
4.29 |
5.10 |
7.77 |
|
LSM difference, 95% CI |
1.686(0.147,3.224) |
3.694(2.172,5.215) |
|
|
p-value |
0.0318 |
<0.0001 |
|
|
FACIT-F |
|
|
|
|
Baseline mean |
27.24 |
22.07 |
26.16 |
|
Mean change from baseline |
6.49 |
9.1 |
10.16 |
|
LSM difference, 95% CI |
|
2.817 (1.552, 4.083) |
3.351 (2.092, 4.611) |
|
p-value |
|
<0.0001 |
<0.0001 |
|
WPAI- % overall work impairment due to RA |
|
|
|
|
Baseline mean |
51.55 |
49.26 |
54.33 |
|
Mean change from baseline |
-9.26 |
-17.84 |
-18.00 |
|
LSM difference, 95% CI |
|
-9.606 (-17.144, -2.068) |
-7.228 (-14.854, 0.397) |
|
p-value |
|
0.0127 |
0.0631 |
|
Sleep VAS |
|
|
|
|
Baseline mean |
54.05 |
53.77 |
54.23 |
|
Mean change from baseline |
-16.89 |
-23.17 |
-23.07 |
|
LSM difference, 95% CI |
|
-6.778 (-10.734, -2.821) |
-6.891(-10.826, -2.955) |
|
p-value |
|
0.0008 |
0.0006 |
|
PCS=Physical Component Summary, LSM=Least Square Means, MCS=Mental Component Summary, PF=Physical Function, RP=Role Physical, BP=Bodily Pain, GH=General Health, VT=Vitality, SF=Social Functioning, RE=Role Emotional, MH=Mental Health & VAS=Visual Analog Scale |
|||
Disclosure:
V. Strand,
Abbvie ,
5,
Amgen,
5,
Anthera,
5,
AstraZeneca/medimmune,
5,
BiogenIdec,
5,
BioMarin,
5,
Celltrion,
5,
BMS,
5,
Genentech/Roche,
5,
GSK,
5,
Hospira,
5,
Incyte,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Lilly,
5,
MerckSerono,
5,
Novartis Pharmaceutical Corporation,
5,
Novo Nordisk,
5,
Pfizer Inc,
5,
Regeneron,
5,
Royalty,
5,
Sanofi – Genzyme ,
5,
Takeda,
5,
UCB,
5,
Vertex,
5;
G. Joseph,
Amgen, Pfizer,
1,
Sanofi,
3;
H. van Hoogstraten,
Sanofi ,
3;
C. I. Chen,
Regeneron,
3;
C. Fan,
Sanofi,
1,
Sanofi,
3;
P. Carita,
Carita,
1,
Carita,
3;
N. Graham,
Regeneron,
1,
Regeneron,
3;
T. Momtahen,
Sanofi ,
1,
Sanofi ,
3;
M. C. Genovese,
Eli Lilly and Company,
2,
Eli Lilly and Company,
5,
Sanofi ,
2,
Sanofi ,
5,
Regeneron,
2,
Regeneron,
5.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-sarilumab-on-health-related-quality-of-life-hrqol-fatigue-and-sleep-in-rheumatoid-arthritis-patients-at-week-24-results-of-a-phase-3-randomized-double-blind-placebo-cont/