Cited by 855Rheumatoid Arthritis Research and TherapiesAutoimmune and Inflammatory Disorders ResearchNatural Compounds in Disease Treatment

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

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

Genovese, Mark C., McKay, James D., Nasonov, Evgeny L., Mysler, Eduardo F., da Silva, Nilzio A., Alecock, Emma, Woodworth, Thasia, Gomez‐Reino, Juan J.·2008·Arthritis & Rheumatism

DOI 10.1002/art.23940

Open this paper in CoChat — free account

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…

Integrity signals

Registry

Crossref · 10.1002/art.23940

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544
Patient-reported outcomes and their role in the assessment of rheumatoid arthritis
Lubeck, D. P. (2004) · PharmacoEconomics · doi:10.2165/00019053-200422001-00004 · Cited by 123

Show all 0 references

Research works printed but not linked: 38

10.1056/NEJM200103223441207 · DOI
Kirwan JR, 2007, Patient perspective: reasons and methods for measuring fatigue in rheumatoid arthritis, J Rheumatol, 34, 1171
10.2146/ajhp050514 · DOI
10.1016/S0140-6736(07)60784-3 · DOI
10.1056/NEJMra032906 · DOI
10.1056/NEJM200011303432202 · DOI
10.1056/NEJM199901283400401 · DOI
10.1002/art.10697 · DOI
10.1186/ar1916 · DOI
10.1073/pnas.90.24.11924 · DOI
10.3109/08830189809042997 · DOI · Paper page
10.1007/BF00307733 · DOI
10.1136/ard.52.3.232 · DOI · Paper page
10.1172/JCI113921 · DOI
10.1002/art.1780310614 · DOI · Paper page
10.1038/ncprheum0338 · DOI
10.1002/art.22033 · DOI · Paper page
10.1136/ard.2006.068064 · DOI
10.1002/art.20303 · DOI
10.1016/S0140-6736(08)60453-5 · DOI
10.1002/art.1780310302 · DOI
10.1002/art.1780380602 · DOI
10.1002/art.1780380107 · DOI
10.1002/art.1780390105 · DOI
10.1002/art.1780230202 · DOI
Cella D, 2005, Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis, J Rheumatol, 32, 811
Ware JE, 1993, SF‐36 health survey: manual and interpretation guide
10.1002/art.1780360601 · DOI
Cohen G, 2005, The efficiency of switching from infliximab to etanercept and vice‐versa in patients with rheumatoid arthritis, Clin Exp Rheumatol, 23, 795
10.1186/ar1881 · DOI
Wolfe F, 2006, Anemia and renal function in patients with rheumatoid arthritis, J Rheumatol, 33, 1516
10.1172/JCI21441 · DOI
10.1196/annals.1351.039 · DOI
10.1007/s10067-007-0539-8 · DOI · Paper page
Vis M, 2005, Short term effects of infliximab on the lipid profile in patients with rheumatoid arthritis, J Rheumatol, 32, 252
10.1186/ar597 · DOI
10.1161/circ.106.25.3143 · DOI · Paper page
10.1136/ard.2004.022061 · DOI

Sorted by citations

Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions
Smolen, J. S., Schoels, M., Nishimoto, N., Breedveld, F. C., Burmester, G. R., Dougados, M., Emery, P., Ferraccioli, G., Gabay, C., Gibofsky, A., et al. (2012) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-202469 · Cited by 122
“41 52 TCZ was also effective as monotherapy.”
Role of proinflammatory cytokines in the pathophysiology of osteoarthritis
Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J.-P., & Fahmi, H. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.196 · Cited by 2,778
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
Smolen, J. S., Landewé, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., van Vollenhoven, R., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210715 · Cited by 2,057
Self-citation
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453
The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis
(2012) · The Lancet · doi:10.1016/s0140-6736(12)60110-x · Cited by 1,146
IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial
Emery, P., Keystone, E., Tony, H. P., Cantagrel, A., van Vollenhoven, R., Sanchez, A., Alecock, E., Lee, J., & Kremer, J. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.092932 · Cited by 1,104
Self-citation
Adverse effects of biologics: a network meta-analysis and Cochrane overview
Singh, J. A., Wells, G. A., Christensen, R., Ghogomu, E. T., Maxwell, L. J., MacDonald, J. K., Filippini, G., Skoetz, N., Francis, D., Lopes, L. C., et al. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008794.pub2 · Cited by 878
IL-6/IL-6 receptor system and its role in physiological and pathological conditions
Mihara, M., Hashizume, M., Yoshida, H., Suzuki, M., & Shiina, M. (2011) · Clinical Science · doi:10.1042/cs20110340 · Cited by 934
Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study
Jones, G., Sebba, A., Gu, J., Lowenstein, M. B., Calvo, A., Gomez-Reino, J. J., Siri, D. A., Tomšič, M., Alecock, E., Woodworth, T., et al. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.105197 · Cited by 797
Self-citation
Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial
Gabay, C., Emery, P., van Vollenhoven, R., Dikranian, A., Alten, R., Pavelka, K., Klearman, M., Musselman, D., Agarwal, S., Green, J., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60250-0 · Cited by 672
Translating IL-6 biology into effective treatments
Choy, E., Benedetti, F. D., Takeuchi, T., Hashizume, M., John, M. R., & Kishimoto, T. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0419-z · Cited by 680
The emerging safety profile of JAK inhibitors in rheumatic disease
Winthrop, K. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.23 · Cited by 583
Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free Causality
Evans, D. M., & Smith, G. D. (2015) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090314-050016 · Cited by 529
“Likewise, a nonsynonymous variant in the IL6R gene is associated with increased levels of circulating IL6, consistent with the action of the IL6R blocker tocilizumab, which has been approved in treating rheumatoid arthritis (54).”
Background
The major inflammatory mediator interleukin-6 and obesity
Éder, K., Baffy, N. J., Falus, A., & Fulop, A. K. (2009) · Inflammation Research · doi:10.1007/s00011-009-0060-4 · Cited by 450
“Plasma lipid levels (total cholesterol, LDL) also increased upon treatment with tocilizumab (at a dose of 8 mg/kg) in an other study (TOWARD, Tocilizumab in combination with traditional DMARD therapy) where patients suffering from rheumatoid arthritis were treated with humanized anti-IL-6 receptor monoclonal antibody…”
Background
Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA
Nam, J., Winthrop, K., van Vollenhoven, R., Pavelka, K., Valesini, G., Hensor, E., Worthy, G., Landewé, R., Smolen, J., Emery, P., et al. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.126573 · Cited by 437
Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: Results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structu
Kremer, J. M., Blanco, R., Brzosko, M., Burgos‐Vargas, R., Halland, A.-M., Vernon, E., Ambs, P., & Fleischmann, R. (2010) · Arthritis & Rheumatism · doi:10.1002/art.30158 · Cited by 405
Tocilizumab: A review in rheumatoid arthritis
Scott, L. J. (2017) · Drugs · doi:10.1007/s40265-017-0829-7 · Cited by 419
“TOWARD (24) [12] DMARD-IR TCZ?DMARD 803 61*** 38*** 21*** 30***”
BackgroundInfluential
Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70
Orme, M., MacGilchrist, K., Mitchell, S., Spurden, D., & Bird, A. (2012) · Biologics : Targets & Therapy · doi:10.2147/btt.s36707 · Cited by 416
“The studies removed for this analysis were Combe et al(42) and Genovese et al.(43) 2.”
Influential
Interleukin-6 in bone metastasis and cancer progression
Ara, T., & DeClerck, Y. A. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.02.026 · Cited by 381
Interleukin-6 as a key player in systemic inflammation and joint destruction
Fonseca, J. E., Santos, M. J., Canhão, H. M., & Choy, E. (2009) · Autoimmunity Reviews · doi:10.1016/j.autrev.2009.01.012 · Cited by 376
Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis
Taylor, P., & Feldmann, M. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.181 · Cited by 391
“IL-6 has been convincingly validated as a molecular therapeutic target by a comprehensive program of clinical trials of a humanized anti-human IL-6 receptor antibody of the κ-IgG 1 subclass”
Background
The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph NodesPreprint
Feng, Z., Diao, B., Wang, R., Wang, G., Wang, C., Tan, Y., Liu, L., Wang, C., Liu, Y., Liu, Y., et al. (2020) · medRxiv · doi:10.1101/2020.03.27.20045427 · Cited by 375
“Tocilizumab, a humanized anti-IL-6 receptor antibody, has been developed and approved for the treatment of rheumatoid arthritis (RA).(30,31) Tocilizumab has also been shown to be effective against cytokine release syndrome resulting from CAR-T cell infusion against B cell acute lymphoblastic leukemia.”
Inflammation and Atherosclerosis
Hartman, J., & Frishman, W. H. (2014) · Cardiology in Review · doi:10.1097/crd.0000000000000021 · Cited by 378
In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494)
Parmentier, J., Voss, J., Graff, C., Schwartz, A., Argiriadi, M., Friedman, M., Camp, H., Padley, R., George, J., Hyland, D., et al. (2018) · BMC Rheumatology · doi:10.1186/s41927-018-0031-x · Cited by 359
Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study
Nishimoto, N., Miyasaka, N., Yamamoto, K., Kawai, S., Takeuchi, T., & Azuma, J. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.092866 · Cited by 333
Immune and Inflammatory Role in Renal Disease
Imig, J. D., & Ryan, M. J. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120028 · Cited by 390
“For example, to-clizumab is a monocolonal antibody against the IL-6 receptor and is currently approved for use in patients with active rheumatoid arthritis (72, 172).”
Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization
Igawa, T., Ishii, S., Tachibana, T., Maeda, A., Higuchi, Y., Shimaoka, S., Moriyama, C., Watanabe, T., Takubo, R., Doi, Y., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1691 · Cited by 349
Integrated safety in tocilizumab clinical trials
Schiff, M. H., Kremer, J. M., Jahreis, A., Vernon, E., Isaacs, J. D., & van Vollenhoven, R. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3455 · Cited by 366
“Data sources and patient populations Included in this analysis are cumulative safety data from five core phase 3 clinical trials: tOcilizumab Pivotal Trial in methotrexate Inadequate respONders (OPTION) [1], Actemra (Roche; Nutley, NJ, USA) versus Methotrexate double-Blind Investigative Trial In mONotherapy (AMBITION)…”
BackgroundResultInfluential
Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis.
Samson, M., Audia, S., Janikashvili, N., Ciudad, M., Trad, M., Fraszczak, J., Ornetti, P., Maillefert, J., Miossec, P., & Bonnotte, B. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34477 · Cited by 342
Flavonoids as Cytokine Modulators: A Possible Therapy for Inflammation-Related Diseases
Leyva-López, N., Gutierrez-Grijalva, E., Ambriz-Perez, D., & Heredia, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060921 · Cited by 337
“For example, when Tocilizumab, an anti-IL-6 receptor widely used in the treatment of rheumatoid arthritis, is used in combination with disease-modifying antirheumatic drugs, an elevation in cholesterol and alanine aminotransferase levels have been reported [61].”
Background
The role of Interleukin 6 in the pathophysiology of rheumatoid arthritis
Srirangan, S., & Choy, E. (2010) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x10378372 · Cited by 371
Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment
Choy, E., Ganeshalingam, K., Semb, A. G., Szekanecz, Z., & Nurmohamed, M. T. (2014) · Rheumatology · doi:10.1093/rheumatology/keu224 · Cited by 310
Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions
Choy, E., & Sattar, N. A. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.101964 · Cited by 296
Risk of Malignancies in Patients With Rheumatoid Arthritis Treated With Biologic Therapy
Lopez-Olivo, M. A., Tayar, J. H., Martínez-López, J. A., Pollono, E. N., Cueto, J. P., Gonzales-Crespo, M. R., Fulton, S., & Suarez-Almazor, M. E. (2012) · JAMA · doi:10.1001/2012.jama.10857 · Cited by 295
How much is too much? Interleukin-6 and its signalling in atherosclerosis
Schuett, H., Luchtefeld, M., Grothusen, C., Grote, K., & Schieffer, B. (2009) · Thrombosis and Haemostasis · doi:10.1160/th09-05-0297 · Cited by 299
Tocilizumab (Actemra)
Sheppard, M., Laskou, F., Stapleton, P., Hadavi, S., & Dasgupta, B. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1316909 · Cited by 305
“more frequently in the TCZ group included headache and hypertension.(45)”
Background
Cytokines as Therapeutic Targets in Rheumatoid Arthritis and Other Inflammatory Diseases
Siebert, S., Tsoukas, A., Robertson, J., & McInnes, I. B. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009639 · Cited by 319
Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor
Dayer, J., & Choy, E. (2009) · Rheumatology · doi:10.1093/rheumatology/kep329 · Cited by 277
Role of interleukin-6 in stress, sleep, and fatigue
Rohleder, N., Aringer, M., & Boentert, M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06634.x · Cited by 289
Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials.
Campbell, L., Chen, C., Bhagat, S., Parker, R., & Östör, A. (2011) · Rheumatology · doi:10.1093/rheumatology/keq343 · Cited by 280
Therapeutic targeting of the interleukin-6 receptor.
Tanaka, T., Narazaki, M., & Kishimoto, T. (2012) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134715 · Cited by 275
NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis
Guo, C., Fu, R., Wang, S., Huang, Y., Li, X., Zhou, M., Zhao, J., & Yang, N. (2018) · Clinical and Experimental Immunology · doi:10.1111/cei.13167 · Cited by 265
Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial
Pérez-Moreiras, J. V., Gómez-Reino, J. J., Maneiro, J. R., Pérez-Pampín, E. M., Lopez, A. R., Rodríguez-Álvarez, F., Laguarta, J. M. C., Cabello, A. D. E., Gessa-Sorroche, M., Gregori, E. E., et al. (2018) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2018.07.038 · Cited by 322
Changes in lipid levels with inflammation and therapy in RA: a maturing paradigm
Robertson, J., Peters, M. J. L., McInnes, I. B., & Sattar, N. A. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2013.91 · Cited by 268
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009
Furst, D. E., Keystone, E. C., Fleischmann, R., Mease, P. J., Fc, B., Smolen, J. S., Kalden, J. R., Braun, J., Bresnihan, B., Burmester, G. R., et al. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.123885 · Cited by 125
Disease–Drug–Drug Interaction Involving Tocilizumab and Simvastatin in Patients With Rheumatoid Arthritis
Schmitt, C., Kuhn, B., Zhang, X.-P., Kivitz, A., & Grange, S. (2011) · Clinical pharmacology and therapy · doi:10.1038/clpt.2011.35 · Cited by 249
“Cmax, ng/ml 36 (22) 14 (6) 43 (33–55) 22 (18) 60 (46–76)”
Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases
Tanaka, T., & Kishimoto, T. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4666 · Cited by 255
Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study
Genovese, M. C., Fleischmann, R., Kivitz, A. J., Rell‐Bakalarska, M., Martincova, R., Fiore, S., Rohane, P., van Hoogstraten, H., Garg, A., Fan, C., et al. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39093 · Cited by 219
Self-citation
Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases
Schultz, O., Oberhauser, F., Saech, J., Rubbert‐Roth, A., Hahn, M., Krone, W., & Laudes, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014328 · Cited by 229
“Several studies have shown increased LDL-cholesterol and triglyceride levels in human subjects when treated with Tocilizumab [21,35,36].”
Background
A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study)
Burmester, G., Rubbert-Roth, A., Cantagrel, A., Hall, S., Leszczyński, P., Feldman, D., Rangaraj, M. J., Roane, G., Ludivico, C., Lu, P., et al. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-203523 · Cited by 243
Self-citation
The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity
Eisenstein, E. M., & Williams, C. B. (2009) · Pediatric Research · doi:10.1203/pdr.0b013e31819e76c7 · Cited by 235
Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial
Huizinga, T. W. J., Fleischmann, R., Jasson, M., Radin, A. R., van Adelsberg, J., Fiore, S., Huang, X., Yancopoulos, G. D., Stahl, N., & Genovese, M. C. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204405 · Cited by 226
Self-citation
Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function
Neveu, W. A., Allard, J. L., Raymond, D. M., Bourassa, L. M., Burns, S. M., Bunn, J. Y., Irvin, C. G., Kaminsky, D. A., & Rincón, M. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-28 · Cited by 203
“However, recent clinical trials with tocilizumab have shown that IL-6 contributes to both disease severity and progression [ 29 ,30].”
Background
Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials
Sieper, J., Porter-Brown, B., Thompson, L., Harari, O., & Dougados, M. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-203559 · Cited by 184
Abatacept treatment for rheumatoid arthritis
Schiff, M. (2010) · Rheumatology · doi:10.1093/rheumatology/keq287 · Cited by 210
Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial
Giles, J., Sattar, N., Gabriel, S., Ridker, P., Gay, S., Warne, C., Musselman, D., Brockwell, L., Shittu, E., Klearman, M., et al. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41095 · Cited by 208
Fatigue in chronic inflammation - a link to pain pathways
Louati, K., & Berenbaum, F. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0784-1 · Cited by 208
“In older patients of the Rotterdam study, despite no association between blood levels of IL-6 and CRP and depressive symptoms, high levels of these inflammatory proteins predicted depressive symptoms 5 years later [74].”
BackgroundInfluential
Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlle
Garnero, P., Thompson, E., Woodworth, T., & Smolen, J. (2010) · Arthritis & Rheumatism · doi:10.1002/art.25053 · Cited by 203
Self-citation
Interleukin-6 in Rheumatoid Arthritis
Pandolfi, F., Franza, L., Carusi, V., Altamura, S., Andriollo, G., & Nucera, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155238 · Cited by 290
“DMARDs normally used in RA do not always offer satisfactory results.”
BackgroundInfluential
Interleukin 6 and Rheumatoid Arthritis
Yoshida, Y., & Tanaka, T. (2014) · BioMed Research International · doi:10.1155/2014/698313 · Cited by 214
Bone Damage in Rheumatoid Arthritis: Mechanistic Insights and Approaches to Prevention
Karmakar, S., Kay, J., & Gravallese, E. M. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.03.003 · Cited by 190
The role and therapeutic targeting of IL-6 in rheumatoid arthritis
Narazaki, M., Tanaka, T., & Kishimoto, T. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1295850 · Cited by 224
“7% of patients receiving TCZ, but without any association between low neutrophil counts and the occurrence of infection-related adverse events during the 6-month study [93].”
Background
Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients
Koike, T., Harigai, M., Inokuma, S., Ishiguro, N., Ryu, J., Takeuchi, T., Takei, S., Tanaka, Y., Ito, K., & Yamanaka, H. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2011.151092 · Cited by 196
Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial
Burmester, G. R., Rigby, W. F., van Vollenhoven, R. F., Kay, J., Rubbert-Roth, A., Kelman, A., Dimonaco, S., & Mitchell, N. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2015-207628 · Cited by 194
Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan
Koike, T., Harigai, M., Inokuma, S., Ishiguro, N., Ryu, J., Takeuchi, T., Takei, S., Tanaka, Y., Sano, Y., Yaguramaki, H., et al. (2014) · Journal of Rheumatology · doi:10.3899/jrheum.130466 · Cited by 194
Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study
Pawar, A., Desai, R. J., Solomon, D. H., Santiago Ortiz, A. J., Gale, S., Bao, M., Sarsour, K., Schneeweiss, S., & Kim, S. C. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-214367 · Cited by 181
Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo.
Wright, H. L., Cross, A., Edwards, S., & Moots, R. (2014) · Rheumatology · doi:10.1093/rheumatology/keu035 · Cited by 190
Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors
Fleischmann, R., van Adelsberg, J., Lin, Y., Castelar‐Pinheiro, G. D. R., Brzezicki, J., Hrycaj, P., Graham, N. M. H., van Hoogstraten, H., Bauer, D., & Burmester, G. R. (2017) · Arthritis & Rheumatology · doi:10.1002/art.39944 · Cited by 178
Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity
Kunz, M., & Ibrahim, S. M. (2009) · Mediators of Inflammation · doi:10.1155/2009/979258 · Cited by 173
IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review
Ogata, A., Kato, Y., Higa, S., & Yoshizaki, K. (2018) · Modern Rheumatology · doi:10.1080/14397595.2018.1546357 · Cited by 212
Therapies for active rheumatoid arthritis after methotrexate failure.
O'Dell, J., Mikuls, T., Taylor, T., Ahluwalia, V., Brophy, M., Warren, S., Lew, R., Cannella, A. C., Kunkel, G., Phibbs, C., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1303006 · Cited by 177
Interleukin-6 as a Multifunctional Regulator: Inflammation, Immune Response, and Fibrosis
Choy, E., & Rose-John, S. (2017) · Journal of Scleroderma and Related Disorders · doi:10.5301/jsrd.5000265 · Cited by 174
“In RA, the role of IL-6 signaling in the development of inflammatory anemia is supported by evidence showing that IL-6R blockade with tocilizumab reduces hepcidin and haptoglobin, as well as CRP, subsequently increasing hemoglobin levels (30).”
Background
The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis
Roy, M. V., Ververken, C., Beirnaert, E., Hoefman, S., Kolkman, J. A., Vierboom, M., Breedveld, E., Hart, B. A. ‘., Poelmans, S., Bontinck, L., et al. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0651-0 · Cited by 189
“6) [46, 47].”
Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions
Nishimoto, N., Ito, K., & Takagi, N. (2010) · Modern Rheumatology · doi:10.3109/s10165-010-0279-5 · Cited by 172
G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis
Cornish, A. L., Campbell, I., McKenzie, B., Chatfield, S., & Wicks, I. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.178 · Cited by 172
The British Society for Rheumatology biologic DMARD safety guidelines in inflammatory arthritis
Holroyd, C., Seth, R., Bukhari, M., Malaviya, A., Holmes, C., Curtis, E., Chan, C. K. Y., Yusuf, M. A., Litwic, A., Smolen, S., et al. (2018) · Rheumatology · doi:10.1093/rheumatology/key208 · Cited by 166
Tocilizumab
Oldfield, V., Dhillon, S., & Plosker, G. (2012) · Drugs · doi:10.2165/00003495-200969050-00007 · Cited by 163
Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammation
Icardi, A., Paoletti, E., De Nicola, L., Mazzaferro, S., Russo, R., & Cozzolino, M. (2013) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gft021 · Cited by 158
Fibroblast‐like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin‐11
Chang, S. K., Gu, Z., & Brenner, M. B. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00854.x · Cited by 158
Systematic Review of Tocilizumab for Rheumatoid Arthritis: A New Biologic targeting the Interleukin-6 Receptor
Navarro-Millán, I., Singh, J. A., & Curtis, J. (2012) · Clinical Therapeutics · doi:10.1016/j.clinthera.2012.02.014 · Cited by 157
Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review
Singh, J. A., Beg, S., & Lopez-Olivo, M. (2011) · Journal of Rheumatology · doi:10.3899/jrheum.100717 · Cited by 155
Lipid Profile Changes in Patients With Chronic Inflammatory Arthritis Treated With Biologic Agents and Tofacitinib in Randomized Clinical Trials: A Systematic Review and Meta‐Analysis
Souto, A., Salgado, E., Maneiro, J., Mera, A., Carmona, L., & Gómez-Reino, J. (2015) · Arthritis & Rheumatology · doi:10.1002/art.38894 · Cited by 154
Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data.
Hoeltzenbein, M., Beck, E., Rajwanshi, R., Skorpen, C. G., Berber, E., Schaefer, C., & Østensen, M. (2016) · Seminars in Arthritis & Rheumatism · doi:10.1016/j.semarthrit.2016.05.004 · Cited by 151
Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)
Sieper, J., Braun, J., Kay, J., Badalamenti, S., Radin, A. R., Jiao, L., Fiore, S., Momtahen, T., Yancopoulos, G. D., Stahl, N., et al. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204963 · Cited by 127
Interleukin‐6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute‐phase reactants
Smolen, J. S., & Aletaha, D. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27740 · Cited by 157
Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome
Shahini, A., & Shahini, A. (2022) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-022-00695-x · Cited by 171
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 148
Janus kinases to jakinibs: from basic insights to clinical practice
Gadina, M., Le, M. T., Schwartz, D. M., Silvennoinen, O., Nakayamada, S., Yamaoka, K., & O’Shea, J. J. (2019) · Rheumatology · doi:10.1093/rheumatology/key432 · Cited by 159
Adult onset Still's disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions.
Maria, A., le Quellec, A., Jorgensen, C., Touitou, I., Riviére, S., & Guilpain, P. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.08.032 · Cited by 147
A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection.
Doberer, K., Duerr, M., Halloran, P., Eskandary, F., Budde, K., Regele, H., Reeve, J., Borski, A., Kozakowski, N., Reindl-Schwaighofer, R., et al. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020071106 · Cited by 145
Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics
Cantini, F., Nannini, C., Niccoli, L., Petrone, L., Ippolito, G., & Goletti, D. (2017) · Mediators of Inflammation · doi:10.1155/2017/8909834 · Cited by 155
Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study
Dougados, M., Kissel, K., Conaghan, P., Mola, E., Schett, G., Gerli, R., Hansen, M., Amital, H., Xavier, R., Troum, O., et al. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204761 · Cited by 143
Pathophysiology and pharmacologic control of osseous mandibular condylar resorption.
Gunson, M., Arnett, G., & Milam, S. (2012) · Journal of oral and maxillofacial surgery · doi:10.1016/j.joms.2011.07.018 · Cited by 143
“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.”
Background
Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis
Favalli, E. G. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00219-2 · Cited by 164
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012
Fürst, D. E., Keystone, E. C., So, A. K.-L., Braun, J., Breedveld, F. C., Burmester, G. R., Benedetti, F. D., Dörner, T., Emery, P., Fleischmann, R., et al. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-203348 · Cited by 120
Phase III Study of the Efficacy and Safety of Subcutaneous Versus Intravenous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis
Ogata, A., Tanimura, K., Sugimoto, T., Inoue, H., Urata, Y., Matsubara, T., Kondo, M., Ueki, Y., Iwahashi, M., Tohma, S., et al. (2014) · Arthritis Care & Research · doi:10.1002/acr.22110 · Cited by 140
Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies
Davis, J. S., Ferreira, D., Paige, E. K., Gedye, C. A., & Boyle, M. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00035-19 · Cited by 193
“tocilizumab is effective in reducing the activity of RA (764, 765).”
Background
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Genovese, M., Rubbert-Roth, A., Smolen, J., Kremer, J., Khraishi, M., Gómez-Reino, J., Sebba, A., Pilson, R., Williams, S., & van Vollenhoven, R. (2013) · Journal of Rheumatology · doi:10.3899/jrheum.120687 · Cited by 139
Self-citation
Clinical Features of Rheumatoid Arthritis
Sweeney, S., Harris, E. D., & Firestein, G. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-3285-4.10066-x · Cited by 138
Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs
Parlakpınar, H., & Günata, M. (2021) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2021.1966033 · Cited by 158
“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)
ORCID: Genovese, Mark C.
McKay, James D.
Nasonov, Evgeny L.
Mysler, Eduardo F.
Woodworth, Thasia
Venue: Arthritis & Rheumatism
Publisher: Wiley
Published: 2008-09-29
Volume: 58
Issue: 10
Pages: 2968-2980
ISSN: 0004-3591 (ISSN-L)
1529-0131
DOI: 10.1002/art.23940
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

Record

About these checks