Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study
Abstract
Objective To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA). Methods A total of 1,220 patients were randomized (2:1 ratio) in the phase III, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks. Results At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P or=1 adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to >3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respecti…
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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 [74]
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 [74]
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Smolen, J. S., & Aletaha, D. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27740 · Cited by 157 · see citing works
Shahini, A., & Shahini, A. (2022) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-022-00695-x · Cited by 167 · see citing works
Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases
Tanaka, T., Narazaki, M., & Kishimoto, T. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.023 · Cited by 144 · see citing works
Janus kinases to jakinibs: from basic insights to clinical practice
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Pathophysiology and pharmacologic control of osseous mandibular condylar resorption.
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“There are 4 published clinical trials using tocilizumab, all of which show prevention of erosions with a low side effect profile.(169-172) Like denosumab, tocilizumab is administered intravenously, and no TMJ studies have been performed.”
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Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012
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Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies
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“tocilizumab is effective in reducing the activity of RA (764, 765).”
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Self-citationClinical Features of Rheumatoid Arthritis
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Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs
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“The alanine transaminase enzyme also increased in at least 5% of patients, but in most cases without symptoms [136].”
Background
- Authors
- Genovese, M. C., McKay, J. D., Nasonov, E. L., Mysler, E. F., da Silva, N. A., Alecock, E., Woodworth, T., & Gomez‐Reino, J. J.
- Affiliations
- Stanford Medicine (US)
- Oklahoma State University at Tulsa (US)
- Association of Rheumatologists of Russia (RU)
- Roche (United Kingdom) (GB)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2008-09-29
- Volume
- 58
- Issue
- 10
- Pages
- 2968-2980
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2063485775
- Cited by
- 855
- References
- 0
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 17 · 2023: 22 · 2022: 28 · 2021: 31 · 2020: 42 · 2019: 32 · 2018: 48 · 2017: 49 · 2016: 57 · 2015: 63 · 2014: 61 · 2013: 82 · 2012: 67
- FWCI
- 51.32
- 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, IL-6 receptor inhibition, rheumatoid arthritis, disease-modifying antirheumatic drugs, combination therapy, inadequate response to DMARDs, ACR20 response, DAS28 remission, C-reactive protein, adverse events, serious infections, alanine aminotransferase elevation, total cholesterol, drug safety
- MeSH terms
- Adult, Aged, Antibodies, Monoclonal, Arthritis, Rheumatoid, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Severity of Illness Index, Antirheumatic Agents, Receptors, Interleukin-6, Antibodies, Monoclonal, Humanized
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