Phase 3
Completed N=162
A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent
Source: ClinicalTrials.gov NCT02046603 ↗Enrolled (actual)
162
Serious AEs
6.2%
Results posted
Dec 2018
Primary outcomePrimary: Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2 — 5.52; 5.53; -1.41; -1.22 units on a scale
◆ Published Evidence
Established
37citations · ~5 / year
Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries.
Summary
This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.
Linked Publications (3)
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Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries.
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Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study.
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Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2 |
5.52; 5.53; -1.41; -1.22 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 4 |
-1.86; -2.11 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 8 |
-2.42; -2.62 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 12 |
-2.33; -2.99 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 16 |
-2.93; -3.07 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 20 |
-3.17; -3.13 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 24 |
-3.28; -3.33 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 28 |
-3.54; -3.32 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 32 |
-3.19; -3.54 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 36 |
-3.57; -3.55 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 40 |
-3.82; -3.64 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 44 |
-3.61; -3.65 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 48 |
-3.54; -3.65 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Week 52 |
-3.75; -3.67 | — |
| PRIMARY Change From Baseline in DAS28-ESR at Early Withdrawal |
-2.88; -1.63 | — |
| SECONDARY Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response |
6; 23; 6; 68; 11; 69 | — |
| SECONDARY Number of Participants Achieving an ACR50 Response |
0; 5; 3; 20; 6; 43 | — |
| SECONDARY Number of Participants Achieving an ACR70 Response |
0; 0; 1; 9; 4; 19 | — |
| SECONDARY Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR |
4; 56; 10; 56; 7; 25 | — |
| SECONDARY Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal |
31.23; 32.33; -9.80; -6.94; -12.64; -13.92 | — |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal |
29.69; 30.88; -8.35; -5.16; -11.87; -12.26 | — |
| SECONDARY Percent Change From Baseline in Total TJC on 68 Joints at Week 52 |
-83.12; -80.44 | — |
| SECONDARY Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal |
10.4; 12.9; -3.4; -2.4; -3.9; -5.4 | — |
| SECONDARY Percent Change From Baseline in Total SJC on 66 Joints at Week 52 |
-89.31; -74.77 | — |
| SECONDARY Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal |
7.0; 5.6; -2.5; -0.8; -4.2; -2.5 | — |
| SECONDARY Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 |
0; 5; 7; 18; 9; 30 | — |
| SECONDARY Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 |
0; 3; 1; 15; 2; 34 | — |
| SECONDARY Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation |
0; 1; 0; 0; 0; 1 | — |
| SECONDARY Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire |
96.82; 92.92; 91.54; 90.14; 95.28; 90.69 | — |
| SECONDARY Patient Global Assessment of Disease Activity VAS Score |
59.6; 62.3; 50.3; 54.5; 46.4; 42.3 | — |
| SECONDARY Patient Pain VAS Score |
50.5; 57.5; 46.1; 51.1; 47.0; 42.4 | — |
| SECONDARY Health Assessment Questionnaire-Disability Index (HAQ-DI) Score |
1.806; 1.738; 1.558; 1.659; 1.616; 1.546 | — |
| SECONDARY Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score |
18.4; 24.3; 23.1; 27.9; 25.1; 30.7 | — |
| SECONDARY Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records |
21; 137; 20; 126; 20; 132 | — |
| SECONDARY Number of Participants With Anti-Tocilizumab Antibodies |
3; 6; 0; 0; 2; 0 | — |
| SECONDARY Serum Levels of Tocilizumab |
0.0000; 0.0082; 35.3953; 40.2529; 53.0416; 43.9047 | — |
| SECONDARY Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) |
43.63; 42.40; 577.42; 548.70; 602.25; 521.07 | — |
Eligibility Criteria
Inclusion Criteria
- Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
- Participants who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28 score improvement of less than 1.2 or participants achieving a DAS28 score improvement of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according to a treat-to-target strategy and have not been previously exposed to treatment with tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed according to local guidelines and the participants will need to be eligible for biologic therapy according to local guidelines
- Oral corticosteroids (≤10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable dose regimen for greater than or equal to [≥] 4 weeks prior to baseline
- Permitted non-biologic DMARDs are allowed if on stable dose for at least 4 weeks prior to baseline
- Receiving treatment on an outpatient basis, not including tocilizumab
- Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of tocilizumab
Exclusion Criteria
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- Rheumatic autoimmune disease other than RA
- Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
- Prior history of or current inflammatory joint disease other than RA
- Exposure to tocilizumab either intravenous or SC at any time prior to baseline
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
- Known active current or history of recurrent infections
- Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active tuberculosis (TB) requiring treatment within the previous 3 years
- Positive for hepatitis B or hepatitis C virus infection
- Primary or secondary immunodeficiency (history of or currently active)
- Pregnant or lactating women
- Inadequate hematologic, renal or liver function
Data sourced from ClinicalTrials.gov (NCT02046603) 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.