Session Information
Date: Sunday, November 8, 2015
Session Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy I: Biologics
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: The investigational agent
sarilumab is a human mAb directed against the IL-6 receptor. The phase 3
MOBILITY study (NCT01061736) evaluated the efficacy and safety of Sarilumab in
combination with MTX in RA patients with inadequate response to MTX.1
The objectives of the phase 3 TARGET study were to evaluate efficacy and safety
of addition of sarilumab to non-biologic DMARD(s) (csDMARDs) in patients (pts)
with active RA.
Methods: Adults with active, moderate-to-severe
RA with inadequate response or intolerance to ≥1 TNF inhibitor(s) were
randomized to placebo (Pbo) (n=181), sarilumab 150 mg q2w (n=181), or sarilumab
200 mg q2w (n=184) subcutaneously + background csDMARD(s) for 24 wks of
treatment in a double-blind fashion. Pts who did not respond adequately to
treatment, starting at wk 12, were rescued with sarilumab 200 mg q2w. Coprimary
endpoints were proportion of pts achieving ACR20 response at wk 24 (nonresponder
imputation) and change from baseline in HAQ-DI at wk 12 (before rescue for
inadequate response). Pts were stratified by region and number of previous
anti-TNFs.
Results: Baseline demographic and disease
characteristics (intention-to-treat population, n=546) were balanced among
treatment groups. A significantly greater proportion of pts receiving either dose
of sarilumab achieved ACR20 responses and significantly improved HAQ-DI scores (Table).
Similar observations were made in the proportion of ACR50, ACR70, and HAQ-DI responders
(HAQ-DI ≥0.22 improvement) at wk 24.
|
|
Placebo + csDMARD (n=181) |
Sarilumab 150 mg q2w + csDMARD (n=181) |
Sarilumab 200 mg q2w + csDMARD (n=184) |
|
Primary endpoints |
|||
|
ACR20 at week 24, % |
34 |
56 |
61 |
|
P value vs placebo |
|
<0.0001 |
<0.0001 |
|
Change from baseline in HAQ-DI at week 12, mean (SD) |
-0.29 (0.54) |
-0.50 (0.64) |
-0.49 (0.56) |
|
P value vs placebo |
|
0.0007 |
0.0004 |
|
Other endpoints |
|||
|
ACR50 at week 24, % |
18 |
37a |
41a |
|
ACR70 at week 24, % |
7 |
20b |
16b |
|
HAQ-DI ≥0.22 at week 24, % |
35 |
48b |
56a |
|
q2w, every 2 wks; SD, standard deviation. aP<0.0001 vs placebo. bP<0.025 vs placebo (to adjust for multiplicity, P values <0.025 are considered statistically significant). |
|||
Treatment-emergent adverse events (TEAEs; safety population,
n=546) were more frequent in sarilumab groups (66% and 65% in sarilumab 150 mg
q2w and 200 mg q2w vs 50% in Pbo). Although incidence of SAEs was higher than Pbo
(3.3%) in the sarilumab 200-mg q2w group (5.4%), they were similar to Pbo in
the 150-mg q2w group (3.3%). Infection was the most frequently reported SAE.
The most frequent events leading to treatment discontinuation were infection
and low absolute neutrophil count (ANC). ANC <1.0 Giga/L was observed in
9.8% of pts in the sarilumab 200-mg q2w group, 7.7% in the sarilumab 150-mg q2w
group, and 0.6% in the Pbo group and was not associated with serious infection.
Laboratory abnormalities included elevations in lipids and transaminases. One
death due to a car accident occurred in the Pbo group.
Conclusion: In this phase 3 study, sarilumab
demonstrated efficacy in pts with active RA who were inadequate responders or intolerant
of anti-TNFs, as evidenced by improvements vs Pbo in signs and symptoms of RA and
in physical function. TEAEs leading to treatment discontinuation were more
frequent in the sarilumab-treated groups. SAEs were more frequent in the
sarilumab 200-mg q2w group. Laboratory findings were consistent with IL-6
blockade and observations from the MOBILITY study.
1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437.
To cite this abstract in AMA style:
Fleischmann R, Castelar-Pinheiro G, Brzezicki J, Hrycaj P, Lin Y, van Adelsberg J, Graham N, van Hoogstraten H, Bauer D, Burmester G. Efficacy and Safety of Sarilumab in Combination with Csdmards in Patients with Active Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant of Anti–TNF-α Therapy: Results from a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-sarilumab-in-combination-with-csdmards-in-patients-with-active-rheumatoid-arthritis-who-were-inadequate-responders-or-intolerant-of-antiaetnf-i%c2%b1-therapy-results-f/. Accessed December 3, 2021.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-sarilumab-in-combination-with-csdmards-in-patients-with-active-rheumatoid-arthritis-who-were-inadequate-responders-or-intolerant-of-antiaetnf-i%c2%b1-therapy-results-f/