Session Information
Date: Monday, November 9, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
Interleukin-6 (IL-6)
is a pleiotropic cytokine known for its proinflammatory functions. In
rheumatoid arthritis (RA), increased concentrations of IL-6 may stimulate leukocyte
recruitment to the joint and promote osteoclast maturation and activation,
contributing to joint damage. Sirukumab is a human anti-IL-6 monoclonal
antibody under development for RA treatment. This study was sponsored
by Janssen in collaboration with GSK.
Methods:
The primary
objective of this study was to assess the safety of sirukumab monotherapy in Japanese
subjects with moderate to severe RA. The study consisted of a 52-week
double-blind treatment phase and a 16-week post-treatment phase. In total, 122 subjects were randomized
1:1 to sirukumab 50mg
every 4 weeks (q4) or sirukumab 100mg every 2 weeks (q2). No disease-modifying
anti-rheumatic drugs (DMARDs) were permitted until Week 24.
Results:
Of the 122
subjects randomized in the 50mg q4 group and the 100mg q2 group, respectively: 77.0%
and 70.5% were female; mean weights were 55.0 and 56.8 kg; mean disease
durations were 7.60 and 7.95 years; and 14 and 10 subjects had experienced treatment
with previous biologics (Table 1).
Safety: In 122 treated
subjects, 56 subjects in the 50mg q4 group and 58 subjects in the 100mg q2
group experienced at least 1 adverse event (AE); there was no marked difference
between the 2 groups. In addition, 9 subjects in the 50mg q4 group and 5 subjects
in the 100mg q2 group discontinued the study agent due to AEs; 23 subjects in
the 50mg q4 group and 24 subjects in the 100mg q2 group experienced injection
site reactions, and 1 subject discontinued due to it. There were no deaths, major
adverse cardiac events, or serious gastrointestinal
perforations. Serious AEs (SAEs) were observed in 4 subjects in the 50mg q4
group and 5 subjects in the 100mg q2 group (Table 2). SAEs of “osteomyelitis”, “borderline serous tumor of ovary”, and “acute
sinusitis” were mild or moderate, and considered reasonably related
to the study drug.
Efficacy: At Week 24, the
proportions of ACR20/50/70 responses were 73.8/49.2/24.6% in the 50mg q4 group and
82.0/63.9/36.1% in the 100mg q2 group. ACR responses were generally maintained through
Week 52.
Conclusion:
Sirukumab 50mg
q4 and 100mg q2 monotherapy dose regimens for 52 weeks were well tolerated in
Japanese RA patients. The proportions of AEs in both groups were similar and there
were no dose-dependent safety issues. The proportions of ACR 20/50/70 responses
at Week 24 in the 100mg q2 group were numerically higher than those in the 50mg
q4 group; however, the number of subjects was too limited to make conclusions
about dose response.
|
Table 1: Demographics and Baseline Characteristics |
||
|
|
Sirukumab, 50mg q4 |
Sirukumab, 100mg q2 |
|
Randomized, n |
61 |
61 |
|
Female, n (%) |
47 (77.0%) |
43 (70.5%) |
|
Age, mean years (SD) |
55.4 (10.7) |
54.7 (12.2) |
|
Weight, mean kg (SD) |
55.0 (12.2) |
56.8 (9.7) |
|
Disease duration, mean years (SD) |
7.60 (8.19) |
7.95 (6.47) |
|
DAS 28 (CRP) score, mean (SD) |
5.6 (0.8) |
5.8 (1.1) |
|
Subjects treated with previous biologics, n (%) |
14 (23.0%) |
10 (16.4%) |
|
Table 2: Summary of Treatment-emergent Adverse Events Through Week 52 |
||
|
|
Sirukumab, 50mg q4 |
Sirukumab, 100mg q2 |
|
Treated, n |
61 |
61 |
|
Any AEs, n (%) |
56 (91.8%) |
58 (95.1%) |
|
Discontinuation due to AEs |
9 (14.8%) |
5 (8.2%) |
|
Injection-site reaction AEs |
23 (37.7%) |
24 (39.3%) |
|
SAEs, n (%) |
4 (6.6%) |
5 (8.2%) |
|
SAEs reasonably related to study drug |
1 (1.6%) |
2 (3.3%) |
|
Serious treatment-emergent infections |
1 (1.6%) |
2 (3.3%) |
|
Malignancies, n (%) |
0 |
1 (1.6%) |
To cite this abstract in AMA style:
Takeuchi T, Yamanaka H, Harigai M, Tamamura R, Kato Y, Ukyo Y, Nakano T, Ota T, Hsu B, Tanaka Y. One-Year Safety of Sirukumab Monotherapy: Results from a Randomized, Double-Blind, Parallel-Group, Multicenter Study in Japanese Subjects with Moderate to Severe Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/one-year-safety-of-sirukumab-monotherapy-results-from-a-randomized-double-blind-parallel-group-multicenter-study-in-japanese-subjects-with-moderate-to-severe-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/one-year-safety-of-sirukumab-monotherapy-results-from-a-randomized-double-blind-parallel-group-multicenter-study-in-japanese-subjects-with-moderate-to-severe-rheumatoid-arthritis/