Session Information
Session Type: Late-Breaking Abstracts
Background/Purpose: The intravenous formulation of tocilizumab (TCZ) has demonstrated efficacy with a manageable safety profile in patients (pts) with rheumatoid arthritis (RA) in multiple clinical trials. Subcutaneous (SC) TCZ would allow pts to have the choice of route of administration, and to self-administer. The objective of this study was to compare the efficacy and safety of TCZ SC versus placebo (PBO) in pts with moderately to severely active RA who had an inadequate response to one or more DMARDs (up to 20% could have failed an anti-TNF agent).
Methods: This 2-year, Phase 3, randomized, multicenter, parallel-group study included a 24-week double-blind, PBO-controlled period followed by open-label treatment for 72-weeks. Data from 24 weeks are presented. Pts were randomized 2:1 to receive TCZ SC 162 mg every other week (q2w) or PBO SC q2w for 24 weeks, in combination with stable doses of pre-study DMARDs. TCZ SC dose was based on previous studies evaluating the PK, PD, efficacy and safety of TCZ SC in pts with RA. Escape therapy with weekly open-label TCZ SC 162 mg was offered at week 12 onwards to pts with less than 20% improvement in both tender and swollen joints. The primary endpoint was to demonstrate superiority of TCZ SC over PBO for ACR20 response at week 24, with a key secondary endpoint being radiographic data. Safety was assessed using AE reports and laboratory results.
Results: The ITT population contained 656 pts (TCZ SC, n = 437; PBO, n = 219). Mean baseline disease characteristics were similar between TCZ SC and PBO groups: age was 52 years; RA duration was 11 years; and DAS28 was 6.7 and 6.6, respectively. Significantly more pts receiving TCZ SC achieved ACR20 responses at Week 24 compared to PBO (60.9% vs 31.5%). Additionally, significantly more pts receiving TCZ SC achieved ACR50 and ACR70 responses and had significantly greater improvements in DAS28 and HAQ-DI scores from baseline compared to PBO at week 24 (Table). Mean change from baseline in mTSS at week 24 was significantly less for pts receiving TCZ SC compared to PBO. Up to week 24, the percentage of pts with AEs and SAEs were comparable in the TCZ SC and PBO groups (Table). The most common AE in both groups was infection. Injection site reactions occurred more frequently in the TCZ SC group compared to the PBO group (7.1% vs 4.1%) but hypersensitivity reactions were similar between the groups (4.3% vs 3.7%). There were no serious hypersensitivity reactions. There were 3 deaths in the TCZ SC group, and none on placebo, however numbers were small.
Conclusion: TCZ SC demonstrated significantly greater efficacy, including ACR end points and inhibition of joint damage, compared to PBO. The AE profile with TCZ SC was comparable to previous studies with TCZ IV. Further results from this 96 week study will extend the findings. TCZ SC is an effective treatment in RA, and will offer an alternative route of administration and the possibility of self-administration for pts.
|
Efficacy and Safety at Week 24 of TCZ SC vs. PBO |
|||
|
|
TCZ SC 162 mg q2w |
PBO SC q2w |
P-value |
|
Efficacy and radiographic outcomes (ITT population) |
|
||
|
N |
437 |
219 |
– |
|
ACR20, % |
60.9 |
31.5 |
< 0.0001 |
|
ACR50, % |
39.8 |
12.3 |
< 0.0001 |
|
ACR70, % |
19.7 |
5.0 |
< 0.0001 |
|
Change in DAS28 from baseline, mean ±SD |
-3.25±1.37 |
-1.79±1.34 |
– |
|
Change in HAQ-DI from baseline, mean ±SD |
-0.50±0.58 |
-0.32±0.59 |
– |
|
Change in mTSS from baseline, mean±SD |
0.62±2.7 |
1.23±2.8 |
0.0149 |
|
Safety assessments (Safety population) |
|
||
|
N |
437 |
218 |
– |
|
Withdrawals, n (%) |
26(5.9) |
7 (3.2) |
– |
|
Escape to open label weekly TCZ SC, n (%) |
72 (16.5) |
90 (41.1) |
– |
|
Patients with ≥ 1 AE, n (%) |
274 (62.7) |
126 (57.8) |
– |
|
Patients with ≥ 1 SAE, n (%) |
20 (4.6) |
8 (3.7) |
– |
|
Patients with ≥ 1 infection, n (%) |
131 (30.0) |
61 (28.0) |
– |
|
Patients with ≥ 1 serious infection, n (%) |
9 (2.1) |
4 (1.8) |
– |
|
Patients with ≥ 1 injection site reaction, n % |
31 (7.1) |
9 (4.1) |
– |
|
Hypersensitivity, n (%) |
19 (4.3) |
8 (3.7) |
– |
|
Deaths, n (%) |
3 (0.7) |
0 (0) |
– |
Disclosure:
A. J. Kivitz,
Genentech and Biogen IDEC Inc.,
2,
Genentech,
5;
E. Olech,
Genentech,
2,
Genentech,
5;
M. A. Borofsky,
None;
B. M. Zazueta,
None;
F. Navarro-Sarabia,
Roche, BMS, Pfizer, UCB, Abbott, Meijii Seika,
5,
Roche, BMS, Pfizer, UCB, Abbott, Meijii Seika,
8;
L. Rowell,
Roche Products Ltd,
3;
C. Nasmyth-Miller,
Roche Products Ltd,
3;
J. E. Pope,
None.
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