Session Information
Date: Tuesday, November 10, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Remission is an important clinical outcome in
RA1 and is associated with improved physical function and health-related
quality of life.2 Several definitions of remission have been proposed on the basis of score thresholds of disease activity measures.3 Recent ACR/EULAR updates to the criteria for remission found a Boolean-based definition (categorical in structure) and SDAI (composite index of RA activity) to be more clinically relevant.3 In the phase 3 MOBILITY study (NCT01061736), both doses of sarilumab (150 or 200 mg every 2 weeks [q2w]) + MTX) demonstrated statistically significant improvement in signs and symptoms of RA, improvement in physical function, and inhibition of radiographic progression.4 The most common treatment-emergent adverse events (TEAEs) with sarilumab included infections, neutropenia, injection site reactions, and increased transaminases. Laboratory changes were consistent with IL-6 signaling blockade. The objective of this prespecified analysis was to assess the ability of sarilumab to induce remission in patients with active, moderate-to-severe RA using 4 different disease activity measures.
Methods: Remission was defined as
DAS28-CRP <2.6, CDAI ≤2.8, SDAI ≤3.3, and Boolean-based ACR/EULAR
remission, which includes tender joint count and swollen joint count (28 joint
count) ≤1, CRP ≤10 mg/L, and patient global VAS ≤10. Patients
who started rescue medication or discontinued study were considered not in
remission. Differences in incidence of DAS28-CRP, CDAI, SDAI, and Boolean
remissions between the active treatment arms and placebo in the ITT population were
assessed using 2-sided Cochran-Mantel-Haenszel tests stratified by prior
biologic use and region.
Results: Baseline demographics and disease characteristics were generally
similar between patients who achieved remission and the general ITT population with
2 exceptions: patients with remission had slightly shorter RA duration and fewer
patients had used prior biologic therapies. Proportion of patients achieving DAS28-CRP,
CDAI, SDAI, and Boolean-based remission at week 24 was higher in the
sarilumab-treated groups vs the placebo group (all P<0.006, except
for Boolean remission in the sarilumab 150 mg q2w group), and these observations
were maintained at week 52 (Table). In all groups, DAS28-CRP remission had the
highest and Boolean-based remission had the lowest frequency.
|
Table. Incidence of Clinical Remission in ITT population |
|||
|
|
Placebo + MTX (n=398) |
Sarilumab 150 mg q2w + MTX (n=400) |
Sarilumab 200 mg q2w + MTX (n=399) |
|
DAS28-CRP remission |
|||
|
Week 24, n (%) P value vs placebo |
40 (10.1) |
111 (27.8) |
136 (34.1) |
|
|
<0.0001 |
<0.0001 |
|
|
Week 52, n (%) P value vs placebo |
34 (8.5) |
124 (31.0) |
136 (34.1) |
|
|
<0.0001 |
<0.0001 |
|
|
CDAI remission |
|||
|
Week 24, n (%) P value vs placebo |
20 (5.0) |
41 (10.3) |
55 (13.8) |
|
|
0.0053 |
<0.0001 |
|
|
Week 52, n (%) P value vs placebo |
19 (4.8) |
59 (14.8) |
72 (18.0) |
|
|
<0.0001 |
<0.0001 |
|
|
SDAI remission |
|||
|
Week 24, n (%) P value vs placebo |
19 (4.8) |
41 (10.3) |
52 (13.0) |
|
|
0.0032 |
<0.0001 |
|
|
Week 52, n (%) P value vs placebo |
16 (4.0) |
60 (15.0) |
74 (18.5) |
|
|
<0.0001 |
<0.0001 |
|
|
Boolean-based ACR/EULAR remission |
|||
|
Week 24, n (%) P value vs placebo |
15 (3.8) |
26 (6.5) |
42 (10.5) |
|
|
0.0810 |
0.0002 |
|
|
Week 52, n (%) P value vs placebo |
12 (3.0) |
42 (10.5) |
56 (14.0) |
|
|
<0.0001 |
<0.0001 |
|
|
ITT, intent-to-treat; MTX, methotrexate; q2w, every 2 weeks. |
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Conclusion: Sarilumab plus MTX induced clinical remission at weeks
24 and 52 as defined by DAS28-CRP, CDAI, SDAI, and Boolean-based remission,
although Boolean-based remission was not achieved for sarilumab 150 mg q2w at
week 24. Remission at week 24 was maintained at week 52.
1. Smolen et al. Ann Rheum Dis. 2015 [Epub ahead of print].
2. Radner et al. Arthritis Res Ther. 2014;16:R56.
3. Felson et al. Ann Rheum Dis. 2011;70:404-413.
4. Genovese et al. Arthritis Rheum. 2015;67:1424-1437.
To cite this abstract in AMA style:
Genovese MC, Stanislav M, van Hoogstraten H, Martincova R, Fan C, van Adelsberg J. Efficacy of Sarilumab Plus Methotrexate in Achieving Clinical Remission, Using 4 Different Definitions, in Patients with Active, Moderate-to-Severe Rheumatoid Arthritis in a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-of-sarilumab-plus-methotrexate-in-achieving-clinical-remission-using-4-different-definitions-in-patients-with-active-moderate-to-severe-rheumatoid-arthritis-in-a-phase-3-study/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-sarilumab-plus-methotrexate-in-achieving-clinical-remission-using-4-different-definitions-in-patients-with-active-moderate-to-severe-rheumatoid-arthritis-in-a-phase-3-study/