Phase 3
Completed N=718
A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX
Source: ClinicalTrials.gov NCT01855789 ↗Enrolled (actual)
718
Serious AEs
10.1%
Results posted
Dec 2017
Primary outcomePrimary: Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40 — 2.13; 2.11; 0.15; 0.48 units on a scale
◆ Published Evidence
Established
50citations · ~6 / year
Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial.
Summary
This randomized, multicenter, double-blind, parallel group study will evaluate the impact of MTX discontinuation on the efficacy of SC TCZ in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants will initiate treatment with TCZ weekly or every 2 weeks along with MTX at a stable dose orally in an open-label manner for 24 weeks. Participants with a disease activity score based on 28 joints (DAS28) less than or equal to (</=) 3.2 at Week 24, will be randomized to either continue receiving a stable dose of MTX or to switch to matching placebo up to Week 52. Participants without a DAS28 score </=3.2 at Week 24, will continue the same treatment in a non-randomized open-label manner up to Week 52.
Linked Publications
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Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40 |
2.13; 2.11; 0.15; 0.48 | — |
| SECONDARY Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) Response |
91.2; 83.0; 78.9; 68.7; 74.1; 65.3 | 0.0746 |
| SECONDARY Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) Response |
74.1; 63.3; 63.9; 50.3; 62.6; 47.6 | 0.0377 sig |
| SECONDARY Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) Response |
45.6; 37.4; 42.2; 34.0; 48.3; 36.7 | 0.3599 |
| SECONDARY Percentage of Participants With >/=1.2 Points Increase (Worsening) From Week 24 in DAS28 Score at Week 40 and 52 |
21.1; 28.6; 26.5; 29.9 | 0.2371 |
| SECONDARY Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission) |
59.2; 49.7; 55.1; 48.3 | 0.1062 |
| SECONDARY Percentage of Participants With DAS28 Score </=3.2 (Low DAS28) |
76.9; 63.3; 68.0; 62.6 | 0.0228 sig |
| SECONDARY Change From Week 24 in Bone Erosion Score at Week 40 for Participants in the Magnetic Resonance Imaging (MRI) Substudy |
10.66; 9.05; -0.10; 0.17 | — |
| SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TCZ |
1.8; 1.5 | — |
| SECONDARY Mean TCZ Serum Concentration |
0.01; 8.66; 23.38; 25.58; 16.46; 6.16 | — |
| SECONDARY Mean Soluble Interleukin-6 (IL-6) Receptor Concentration |
40.4; 366.4; 441.3; 468.9; 336.3; 166.8 | — |
Eligibility Criteria
Inclusion Criteria
- Body weight /=4.4) according to the revised 1987 ACR criteria at screening and baseline (prior to treatment on Day 1)
- Currently receiving oral MTX for at least 24 weeks and on a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1), with the following exception: a stable dose of at least 10 mg/week is allowed for participants with a body weight /=15 mg/week
- Participants receiving other (non-MTX) disease modifying anti-rheumatic drugs (DMARDs) within 8 weeks of screening
- Previous treatment with abatacept, rituximab, tofacitinib, or anakinra
- Treatment with parenteral corticosteroids within 4 weeks prior to treatment
- Previous treatment with cell-depleting therapies or alkylating agents
- Previous treatment with TCZ
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery during the study
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Non-rheumatic active autoimmune diseases (for example, inflammatory bowel diseases, psoriasis, multiple sclerosis)
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Functional Class IV according to the revised (1987) ACR criteria for rheumatoid arthritis
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Evidence of significant uncontrolled concomitant diseases; uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids
- Active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
- Active tuberculosis requiring treatment within the previous 3 years
- History of or currently active primary or secondary immunodeficiency
- Pregnant or breast-feeding women
- Positive for hepatitis B or hepatitis C infection
- For potential MRI substudy participants: the presence of any metal-containing device or object in the body
Data sourced from ClinicalTrials.gov (NCT01855789) and the linked publication. 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.