Phase 4
Completed N=259
Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants
Source: ClinicalTrials.gov NCT02573012 ↗Enrolled (actual)
259
Serious AEs
4.3%
Results posted
Jul 2019
Primary outcomePrimary: Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization — 0.538; -0.075 Score on a scale — p=0.001
◆ Published Evidence
Highly cited
125citations · ~21 / year
Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.
Summary
This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial compares the change in disease activity (as assessed by Disease Activity Score in 28 joints [DAS28] erythrocyte sedimentation rate [ESR]) from randomization to Week 24 post-randomization, in participants with stable low disease activity [LDA] (DAS28 ESR score less than or equal to [<=] 3.2) who receive tocilizumab, and have been randomized to either continue or taper prednisone in a double-blinded fashion.
Linked Publications
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Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization |
0.538; -0.075 | 0.001 sig |
| SECONDARY Treatment Success |
64.9; 77.3 | 0.018 sig |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 |
2.663; 0.321 | 0.006 sig |
| SECONDARY Percentage of Participants With >=1 Flare |
26.0; 10.9 | — |
| SECONDARY Time to First RA Flare |
15.64; 12.11 | — |
| SECONDARY Percentage of Visits With RA Flares |
16.0; 7.0; 6.9; 3.9; 2.3; 0 | — |
| SECONDARY Percentage of Participants With >=1 Administration of Flare Rescue Medication |
20.6; 6.3 | — |
| SECONDARY Time to First Administration of Flare Rescue Medication |
13.59; 8.76 | — |
| SECONDARY Number of Administrations of Flare Rescue Medication |
79.4; 93.8; 15.3; 3.9; 4.6; 1.6 | — |
| SECONDARY Cumulative Prednisone Exposure (Dose) |
267.099; 769.459; 98.519; 121.875; 287.405; 777.136 | — |
| SECONDARY Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level |
97.7; 96.9; 73.4; 83.1; 78.6; 76.6 | — |
| SECONDARY Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control |
0; 0.8 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts |
0.129; -0.107 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts |
0.793; -0.330 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain |
4.648; -8.010 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity |
0.280; -0.153 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity |
0.345; -0.248 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI) |
0.167; -0.087 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) |
-0.135; -0.040 | — |
| SECONDARY Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR) |
1.517; -0.679 | — |
| SECONDARY Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score |
0.469; -0.220 | — |
| SECONDARY Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score |
4.535; 0.572; -0.851; -5.584; 6.219; -6.191 | — |
| SECONDARY Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24 |
2.511; 0.248 | 0.009 sig |
Eligibility Criteria
Inclusion Criteria
Tocilizumab-experienced participants:
- Comply with the requirements of the study protocol (including treatment on an outpatient basis)
- Rheumatoid arthritis (RA) of greater than or equal to (>=) 6 months duration diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010 ACR / European League Against Rheumatism (EULAR) criteria
- Have received tocilizumab either subcutaneous (162 milligram [mg] once in a week) or intravenously (8 milligram per kilogram [mg/kg] once every 4 weeks) for the treatment of RA for at least 24 weeks prior to randomization
- Have received 5 - 15 milligrams per day [mg/day] of glucocorticoids (prednisone or equivalent) for the treatment of RA for at least 20 weeks prior to screening
- Currently receiving 5 mg/day of prednisone
- Have attained and maintained LDA (DAS28 ESR score =6 months duration diagnosed according to the revised 1987 ACR criteria or 2010 ACR / EULAR criteria
- Have active RA (defined as DAS28 ESR score greater than [>] 3.2)
- Are considered by the investigator as inadequate responders to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs)
- Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA
Exclusion Criteria
General
- Major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery during the study and up to 6 months after randomization
- Pregnant women or nursing (breastfeeding) mothers
- In females of childbearing potential, a positive serum pregnancy test at screening
- Females of childbearing potential unwilling or unable to use a reliable means of contraception (for example, physical barrier [participant or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during study treatment and for a minimum of 3 months after the last dose of tocilizumab
- Body weight of >=150 kilogram (kg)
- Lack of peripheral venous access
Disease-related
- RA of functional Class 4, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the investigator
- Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 years
- Prior or current inflammatory joint disease other than RA (for example, gout, Lyme disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease), or prior or current joint infections
- Previous history of primary or secondary adrenal insufficiency
Previous or Concomitant Prohibited Therapy
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD20)
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of screening
- Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4 weeks prior to screening
- Previous treatment with glucocorticoids for conditions other than RA, at any dose and in any formulation used continuously for >1 week, during the last 1 year prior to screening. Topical glucocorticoid creams or ointments for the treatment of skin conditions (for example eczema) are allowed
- Immunization with a live/attenuated vaccine within 30 days prior to screening. Participants must agree not to take live attenuated vaccines (including seasonal nasal flu va
Data sourced from ClinicalTrials.gov (NCT02573012) 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.