Phase 3
Completed N=556
A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment
Source: ClinicalTrials.gov NCT00810199 ↗Enrolled (actual)
556
Serious AEs
17.5%
Results posted
Jul 2014
Primary outcomePrimary: Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24 — 40.4; 34.8 Percentage of participants — p=0.2055
Summary
This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24 |
40.4; 34.8 | 0.2055 |
| SECONDARY Percentage of Participants With American College of Rheumatology (ACR20) Response |
71.5; 70.3; 70.8; 69.2; 65.7; 59.4 | 0.8742 |
| SECONDARY Percentage of Participants With ACR50 Response |
45.5; 40.2; 50.2; 55.4; 52.7; 46.4 | 0.2969 |
| SECONDARY Percentage of Participants With ACR70 Response |
24.5; 25.4; 31.4; 31.2; 34.3; 29.3 | 0.6775 |
| SECONDARY Percentage of Participants With ACR90 Response |
5.8; 5.1; 12.6; 11.2; 11.9; 9.1 | 0.8369 |
| SECONDARY Time to First ACR20 Response |
57.0; 61.0 | 0.1018 |
| SECONDARY Time to First ACR50 Response |
140.0; 143.0 | 0.7176 |
| SECONDARY Time to First ACR70 Response |
284.0; 307.0 | 0.8526 |
| SECONDARY Time to First ACR90 Response |
NA; NA | 0.2217 |
| SECONDARY Area Under Curve (AUC) DAS28 |
3.97; 4.23 | 0.0008 sig |
| SECONDARY Percentage of Participants With Disease Activity Score 28 (DAS28) Remission |
45.5; 36.6 | 0.0245 sig |
| SECONDARY Percentage of Participants With DAS28 Low Disease Activity (LDAS) |
61.7; 51.4; 62.5; 57.2 | 0.0287 sig |
| SECONDARY Change From Baseline in DAS28 Score |
-3.43; -3.21; -3.74; -3.67 | 0.0497 sig |
| SECONDARY Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses |
89.5; 86.2; 84.5; 78.2 | 0.0019 sig |
| SECONDARY Change From Baseline in Swollen Joint Count |
-11.33; -11.74; -12.29; -12.25 | 0.7776 |
| SECONDARY Change From Baseline in Tender Joint Count |
-17.27; -17.00; -19.45; -18.97 | 0.9095 |
| SECONDARY Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) |
-34.31; -32.42; -38.92; -40.94 | 0.3113 |
| SECONDARY Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS) |
-40.67; -38.46; -44.18; -44.68 | 0.2451 |
| SECONDARY Change From Baseline in Patient Global Assessment of Pain (VAS) |
-29.34; -29.75; -33.09; -38.38 | 0.9655 |
| SECONDARY Change From Baseline in Erythrocyte Sedimentation Rate (ESR) |
-30.61; -29.10; -31.81; -31.18 | 0.5186 |
| SECONDARY Change From Baseline in C-Reactive Protein (CRP) |
-1.37; -1.39; -1.39; -1.40 | 0.6067 |
| SECONDARY Change From Baseline in the Health Assessment Questionnaire Disability Index |
-0.56; -0.55; -0.59; -0.67 | 0.9323 |
| SECONDARY Change From Baseline in Total Genant Modified Sharp Scores (GSS) |
0.18; 0.35; 0.35; 0.63; 0.35; 0.95 | 0.2034 |
| SECONDARY Change From Baseline in Joint Space Narrowing Score |
0.16; 0.19; 0.45; 0.39; 0.38; 0.70 | 0.7095 |
| SECONDARY Change From Baseline in Erosion Score |
0.03; 0.15; -0.09; 0.25; -0.03; 0.26 | 0.0441 sig |
| SECONDARY Percentage of Participants Discontinuing Tocilizumab Due to Remission |
28.4; 21.6; 53.1; 47.6 | 0.0694 |
| SECONDARY Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response |
1.8; 4.7 | 0.0496 sig |
| SECONDARY Percentage of Participants Who Withdrew Due to Safety Reasons |
9.7; 11.2 | 0.5188 |
| SECONDARY Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) |
-6.07; -5.19; -7.28; -6.33; -6.89; -5.24 | 0.2652 |
| SECONDARY Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS) |
2.42; 0.91 | — |
| SECONDARY Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response |
18.95; 13.74 | 0.1110 |
| SECONDARY Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response |
30.48; 32.59 | 0.6027 |
| SECONDARY Time to Tocilizumab Remission |
645.0; 786.0 | 0.1695 |
| SECONDARY Time to Drug-Free Remission |
NA; NA | 0.0096 sig |
| SECONDARY Time to Flare After Tocilizumab Remission |
113.0; 84.0 | 0.0734 |
| SECONDARY Time to Restart of Treatment After Discontinuation/Remission |
113.0; 81.0 | — |
Eligibility Criteria
Inclusion Criteria
- adult patients, ≥ 18 years of age;
- moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
- inadequate response to methotrexate;
- on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.
Exclusion Criteria
- prior treatment with a biologic;
- Rheumatoid arthritis (RA) functional class IV;
- known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
- evidence of active malignant disease.
Data sourced from ClinicalTrials.gov (NCT00810199). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.