Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The MIRAI study evaluates a sequential exposure to two defined biologics under rigorous study conditions within a homogeneous population of patients (pts) who inadequately responded to traditional disease modifying anti-rheumatic drugs (DMARD-IR). This study investigates the early response to the IL-6 inhibitor tocilizumab (TCZ) in rheumatoid arthritis (RA) patients; non-responders to TCZ will subsequently receive 1 cycle of rituximab (RTX; anti-CD20 therapy).
Methods:
We report the results of a 2nd interim analysis (first-pat-in: MAR-2011; last-pat-in: FEB-2013) of MIRAI (NCT01332994), an ongoing, German, multicenter, two-arm, open-label, phase-III-study in DMARD-IR pts with moderate to severe active RA, DAS28>3.2, biological naïve and on ≥1 concomitant traditional DMARD. All pts received 4 TCZ infusions (8 mg/kg, q4w; 1st treatment period) until week 16. Partial responders (ΔDAS28<1.2 or DAS28≥2.6 and ≤3.2) received further 4 TCZ infusions (8 mg/kg, q4w); non-responders (ΔDAS28<1.2 and DAS28>3.2) received a subsequent biological treatment with RTX (1g each at weeks 16 and 18). All pts with a 2nd treatment period (TCZ or RTX) will complete study at week 32. Primary endpoint: patients in remission (DAS28<2.6) at week 16. Secondary endpoints include: DAS28<2.6 at week 32, ACR response, adverse events (AE).
Results:
510 pts (ITT-Main; mean age: 56 years, females 68.2%) entered the first treatment period and received TCZ. All pts had previously received DMARDs (mostly methotrexate, 412 pts). 432 pts (85%) completed week 16, 155 pts (30%) completed week 32. At week 16, 186 pts (36%) initiated a second TCZ treatment period (ITT-TCZ2) and 24 pts (4.7%) received a subsequent RTX therapy (ITT-RTX). At week 16, efficacy parameters had improved considerably in the ITT-Main population. At week 32, further improvement was seen in all efficacy parameters under continued TCZ therapy (ITT-TCZ2); up to now, the few pts who received a subsequent RTX therapy showed slight improvements (ITT-RTX).
|
Parameter |
Baseline |
Week 16 |
Week 32 |
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|
ITT-Main |
|||||
|
DAS28, mean ± SD |
5.7 ± 1.0 (N=507) |
2.6 ±1.3 (N=423) |
2.7 ± 1.4 (N=150) |
||
|
VAS DA pat, mean ± SD |
63.3 ± 20.6 (N=509) |
26.3 ± 22.5 (N=429) |
28.9 ± 25.3 (N=155) |
||
|
SJC28, mean ± SD |
8.3 ± 4.9 (N=509) |
3.2 ± 3.6 (N=425) |
3.0 ± 3.9 (N=152) |
||
|
VAS pain, mean ± SD |
63.5 ± 21.1 (N=509) |
27.2 ± 22.9 (N=429) |
29.1 ± 24.6 (N=155) |
||
|
HAQ-DI, mean ± SD |
1.25 ± 0.66 (N=428) |
0.73 ± 0.67 (N=292) |
0.83 ± 0.70 (N=101) |
||
|
ITT-TCZ2 |
|||||
|
DAS28, mean ± SD |
6.0 ± 0.9 (N=186) |
3.2 ± 0.7 (N=184) |
2.5 ± 1.3 (N=131) |
||
|
VAS DA pat, mean ± SD |
66.9 ± 19.2 (N=186) |
30.3 ± 20.5 (N=186) |
26.8 ± 24.0 (N=136) |
||
|
SJC28, mean ± SD |
9.4 ± 4.8 (N=186) |
4.1 ± 3.2 (N=185) |
2.7 ±3.5 (N=133) |
||
|
VAS pain, mean ± SD |
66.2 ± 19.2 (N=186) |
31.2 ± 20.6 (N=186) |
27.0 ± 23.4 (N=136) |
||
|
HAQ-DI, mean ± SD |
1.27 ± 0.66 (N=174) |
0.81 ± 0.66 (N=124) |
0.77 ± 0.69 (N=88) |
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|
ITT-RTX |
|||||
|
DAS28, mean ± SD |
5.7 ± 1.0 (N=24) |
5.2 ± 1.2 (N=24) |
4.2 ± 1.6 (N=18) |
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|
VAS DA pat, mean ± SD |
64.6 ± 18.3 (N=24) |
58.5 ± 22.6 (N=24) |
43.8 ± 31.0 (N=18) |
||
|
SJC28, mean ± SD |
9.5 ± 6.4 (N=24) |
9.0 ± 6.1 (N=24) |
4.7 ± 5.7 (N=18) |
||
|
VAS pain, mean ± SD |
67.6 ± 17.2 (N=24) |
57.6 ± 22.7 (N=24) |
45.1 ± 28.9 (N=18) |
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|
HAQ-DI, mean ± SD |
1.31 ± 0.64 (N=20) |
1.49 ± 0.75 (N=17) |
1.26 ± 0.70 (N=12) |
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|
Data are presented “as-observed”. DAS = Disease Activity Score; HAQ-DI = Health Assessment Questionnaire-Disability Index; SD = Standard Deviation; SJC28 = Swollen Joint Count (28 joints); VAS = Visual Analogue Scale. |
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The total incidence of AEs/serious AEs with a suspected causal relationship to treatment is 30.4%/4.1%. SAEs suspected to be causally related to TCZ include 2 cases each of diverticulitis, pneumonia and elevated liver enzymes; 1 case each of atrial fibrillation; neutropenia plus leucopenia; thrombopenia. One death with a suspected causal relationship to TCZ was reported (fall plus craniocerebral injury). Up to now, no SAEs suspected to be causally related to RTX have been reported.
Conclusion:
Early response to TCZ was demonstrated by a substantial improvement in all efficacy parameters within the first 16 weeks of treatment. Initially partial responders to TCZ benefited from a continued TCZ therapy. Notably, the proportion of TCZ non-responders who received a subsequent RTX-treatment was low.
Disclosure:
T. Doerner,
Roche Pharmaceutical, Chugai Pharma,
5,
Roche Pharmaceuticals, Chugai Pharma,
9;
H. P. Tony,
Roche Pharmaceuticals,
5;
H. Schulze-Koops,
Roche Pharmaceuticals,
5,
Roche Pharmaceuticals,
8;
J. Kaufmann,
None;
P. Kaestner,
None;
H. Kellner,
None;
R. Kurthen,
None;
S. Wagner,
None;
M. A. Peters,
Roche Pharmaceuticals,
3;
C. Iking-Konert,
Roche Pharmaceuticals,
5.
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