Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate
Abstract
Objective To establish the safety and efficacy of repeat infusions of tocilizumab (previously known as MRA), a humanized anti-interleukin-6 (IL-6) receptor antibody, alone and in combination with methotrexate (MTX), for the treatment of rheumatoid arthritis (RA). Methods The study group comprised 359 patients with active RA in whom the response to MTX was inadequate. During a stabilization period, these patients received their current dose of MTX for at least 4 weeks. Following stabilization, they were randomized to 1 of 7 treatment arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg, or 8 mg/kg either as monotherapy or in combination with MTX, or MTX plus placebo. Results A 20% response (improvement) according to the American College of Rheumatology criteria (ACR20 response) was achieved by 61% and 63% of patients receiving 4 mg/kg and 8 mg/kg of tocilizumab as monotherapy, respectively, and by 63% and 74% of patients receiving those doses of tocilizumab plus MTX, respectively, compared with 41% of patients receiving placebo plus MTX. Statistically significant ACR50 and ACR70 responses were observed in patients receiving combination therapy with either 4 mg/kg or 8 mg/kg of tocilizumab plus MTX (P Conclusion These results indicate that targeted blockade of IL-6 signaling is a highly efficacious and promising means of decreasing disease activity in RA.
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A humanized monoclonal antibody against IL-6 receptor, tocilizumab, has proven successful for treating rheumatoid arthritis and Castleman's disease.
“Instead of murine MoAb against IL-6, a humanized MoAb against IL-6 receptor (IL-6R), tocilizumab, has proven successful for treating RA and Castleman’s disease (71–75).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [73]
The anti-IL-6R antibodies tocilizumab and sarilumab are used to treat RA, Castleman's disease and CAR-T-induced CRS.
“The anti-IL-6R antibodies tocilizumab and sarilumab are used to treat RA, Castleman’s disease and CAR-T-induced CRS (71–75, 352, 364) and have promise for treating the severe form of COVID-19 (365–367).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [73]
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- Authors
- Maini, R. N., Taylor, P. C., Szechinski, J., Pavelka, K., Bröll, J., Balint, G., Emery, P., Raemen, F., Petersen, J., Smolen, J., Thomson, D., & Kishimoto, T.
- Affiliations
- Imperial College London (GB)
- University of Leeds (GB)
- Copenhagen University Hospital (DK)
- Medical University of Vienna (AT)
- Chugai Pharma Europe Limited (United Kingdom) (GB)
- The University of Osaka (JP)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2006-08-31
- Volume
- 54
- Issue
- 9
- Pages
- 2817-2829
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2125212735
- Cited by
- 790
- References
- 0
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 15 · 2023: 13 · 2022: 20 · 2021: 19 · 2020: 26 · 2019: 25 · 2018: 30 · 2017: 39 · 2016: 40 · 2015: 52 · 2014: 45 · 2013: 59 · 2012: 57
- FWCI
- 41.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- tocilizumab, rheumatoid arthritis, IL-6 receptor inhibitor, methotrexate, inadequate response to methotrexate, combination therapy, monotherapy, dose-response relationship, ACR20 response, DAS28, C-reactive protein, erythrocyte sedimentation rate, liver enzymes, lipoprotein levels, neutrophil count, drug safety
- MeSH terms
- Antibodies, Monoclonal, Arthritis, Rheumatoid, Dose-Response Relationship, Drug, Europe, Female, Humans, Male, Methotrexate, Middle Aged, Pain, Safety, Treatment Outcome, Treatment Failure, Antirheumatic Agents, Patient Selection, Receptors, Interleukin-6, Antibodies, Monoclonal, Humanized
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