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Erschienen in: Wiener Medizinische Wochenschrift 1-2/2015

01.01.2015 | main topic

IL-6 blockade in chronic inflammatory diseases

verfasst von: MD Antonia Puchner, MD Stephan Blüml

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 1-2/2015

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Summary

Proinflammatory cytokines are centrally involved in the pathogenesis of various rheumatic diseases. Interleukin (IL)-6 is a prototypic representative of this family. Basic research has uncovered a multitude of functions for this cytokine, such as immune regulation, hematopoiesis, inflammation, and oncogenesis (Fig. 1). In recent years, agents blocking the actions of IL-6 have been developed for the therapy of rheumatologic inflammatory diseases. While in some diseases, most notably rheumatoid arthritis, the clinical efficacy of these drugs was excellent, the results of clinical trials in other chronic inflammatory diseases were heterogeneous. In this review, we will summarize the data currently available on IL-6 blockade in chronic inflammatory diseases and will also discuss the safety issues of blocking this cytokine.

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Literatur
1.
Zurück zum Zitat Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, Investigators O. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371:987–97. CrossRefPubMed Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, Investigators O. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371:987–97. CrossRefPubMed
2.
Zurück zum Zitat Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ. 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. Arthritis Rheum. 2008;58:2968–80. CrossRefPubMed Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ. 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. Arthritis Rheum. 2008;58:2968–80. CrossRefPubMed
3.
Zurück zum Zitat Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. 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. Ann Rheum Dis. 2008;67:1516–23. CrossRefPubMedCentralPubMed Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. 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. Ann Rheum Dis. 2008;67:1516–23. CrossRefPubMedCentralPubMed
4.
Zurück zum Zitat Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum. 2011;63:43–52. CrossRefPubMed Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum. 2011;63:43–52. CrossRefPubMed
5.
Zurück zum Zitat Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, Ambs P, Fleischmann R. 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 structural joint damage at one year. Arthritis Rheum. 2010;63:609–21. CrossRef Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, Ambs P, Fleischmann R. 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 structural joint damage at one year. Arthritis Rheum. 2010;63:609–21. CrossRef
6.
Zurück zum Zitat Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2009;69:88–96. CrossRefPubMedCentral Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2009;69:88–96. CrossRefPubMedCentral
7.
Zurück zum Zitat Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Murata N, van der Heijde D, Kishimoto T. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007;66:1162–7. CrossRefPubMedCentralPubMed Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Murata N, van der Heijde D, Kishimoto T. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007;66:1162–7. CrossRefPubMedCentralPubMed
8.
Zurück zum Zitat Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, Kishimoto T. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19:12–9. CrossRefPubMedCentralPubMed Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, Kishimoto T. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19:12–9. CrossRefPubMedCentralPubMed
9.
Zurück zum Zitat Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26–37. CrossRefPubMed Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26–37. CrossRefPubMed
10.
Zurück zum Zitat Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, Schett G, Amital H, Navarro-Sarabia F, Hou A, et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013;72:43–50. CrossRefPubMedCentralPubMed Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, Schett G, Amital H, Navarro-Sarabia F, Hou A, et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013;72:43–50. CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, Hansen MS, Amital H, Xavier RM, Troum O, et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73:803–9. CrossRefPubMedCentralPubMed Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, Hansen MS, Amital H, Xavier RM, Troum O, et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73:803–9. CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2011;38:10–20. CrossRefPubMed Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2011;38:10–20. CrossRefPubMed
13.
Zurück zum Zitat Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2013;72:482–92. CrossRefPubMedCentralPubMed Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2013;72:482–92. CrossRefPubMedCentralPubMed
14.
Zurück zum Zitat Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum. 2010;63:43–52. CrossRef Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum. 2010;63:43–52. CrossRef
15.
Zurück zum Zitat Schiff MH, Kremer JM, Jahreis A, Vernon E, Isaacs JD, van Vollenhoven RF. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011;13:R141. CrossRefPubMedCentralPubMed Schiff MH, Kremer JM, Jahreis A, Vernon E, Isaacs JD, van Vollenhoven RF. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011;13:R141. CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Campbell L, Chen C, Bhagat SS, Parker RA, Ostor AJ. 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. Rheumatology (Oxford). 2011;50:552–62. CrossRefPubMed Campbell L, Chen C, Bhagat SS, Parker RA, Ostor AJ. 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. Rheumatology (Oxford). 2011;50:552–62. CrossRefPubMed
17.
Zurück zum Zitat Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, Filippini G, Skoetz N, Francis D, Lopes LC, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011:CD008794. Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, Filippini G, Skoetz N, Francis D, Lopes LC, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011:CD008794.
18.
Zurück zum Zitat Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886–95. CrossRefPubMed Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886–95. CrossRefPubMed
19.
Zurück zum Zitat Gout T, Ostor AJ, Nisar MK. Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol. 2011;30:1471–4. CrossRefPubMed Gout T, Ostor AJ, Nisar MK. Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol. 2011;30:1471–4. CrossRefPubMed
20.
Zurück zum Zitat Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2013;72:482–92. CrossRefPubMedCentralPubMed Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2013;72:482–92. CrossRefPubMedCentralPubMed
21.
Zurück zum Zitat Md Yusof MY, Emery P. Targeting interleukin-6 in rheumatoid arthritis. Drugs. 2013;73:341–56. CrossRefPubMed Md Yusof MY, Emery P. Targeting interleukin-6 in rheumatoid arthritis. Drugs. 2013;73:341–56. CrossRefPubMed
22.
Zurück zum Zitat Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. 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. Ann Rheum Dis. 2009;68:1580–4. CrossRefPubMedCentralPubMed Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. 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. Ann Rheum Dis. 2009;68:1580–4. CrossRefPubMedCentralPubMed
23.
Zurück zum Zitat McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis. 2013;73:349–56. CrossRefPubMed McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis. 2013;73:349–56. CrossRefPubMed
24.
Zurück zum Zitat Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C, et al. Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014;73:1607–15. Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C, et al. Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014;73:1607–15.
25.
Zurück zum Zitat Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC. Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73:1626–34. Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC. Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73:1626–34.
26.
Zurück zum Zitat Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014;73:1616–25. Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014;73:1616–25.
27.
Zurück zum Zitat Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu LA, Liu Y, Smith J. A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis. 2012;71:1183–9. CrossRefPubMed Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu LA, Liu Y, Smith J. A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis. 2012;71:1183–9. CrossRefPubMed
28.
Zurück zum Zitat Gratacos J, Collado A, Filella X, Sanmarti R, Canete J, Llena J, Molina R, Ballesta A, Munoz-Gomez J. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol. 1994;33:927–31. CrossRefPubMed Gratacos J, Collado A, Filella X, Sanmarti R, Canete J, Llena J, Molina R, Ballesta A, Munoz-Gomez J. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol. 1994;33:927–31. CrossRefPubMed
29.
Zurück zum Zitat Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, Yorgancioglu R. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol. 2007;26:211–5. CrossRefPubMed Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, Yorgancioglu R. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol. 2007;26:211–5. CrossRefPubMed
30.
Zurück zum Zitat Falkenbach A, Herold M. In ankylosing spondylitis serum interleukin-6 correlates with the degree of mobility restriction, but not with short-term changes in the variables for mobility. Rheumatol Int. 1998;18:103–6. CrossRefPubMed Falkenbach A, Herold M. In ankylosing spondylitis serum interleukin-6 correlates with the degree of mobility restriction, but not with short-term changes in the variables for mobility. Rheumatol Int. 1998;18:103–6. CrossRefPubMed
31.
Zurück zum Zitat Hayer S, Niederreiter B, Nagelreiter I, Smolen J, Redlich K. Interleukin-6 is not a crucial regulator in tumour necrosis factor-mediated bilateral sacroiliitis. Ann Rheum Dis. 2010;69:1403–6. Hayer S, Niederreiter B, Nagelreiter I, Smolen J, Redlich K. Interleukin-6 is not a crucial regulator in tumour necrosis factor-mediated bilateral sacroiliitis. Ann Rheum Dis. 2010;69:1403–6.
32.
Zurück zum Zitat Sieper J, Porter-Brown B, Thompson L, Harari O, Dougados M. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis.2014;73:95–100. CrossRefPubMedCentralPubMed Sieper J, Porter-Brown B, Thompson L, Harari O, Dougados M. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis.2014;73:95–100. CrossRefPubMedCentralPubMed
33.
Zurück zum Zitat Ogata A, Umegaki N, Katayama I, Kumanogoh A, Tanaka T. Psoriatic arthritis in two patients with an inadequate response to treatment with tocilizumab. Joint Bone Spine. 2012;79:85–7. CrossRefPubMed Ogata A, Umegaki N, Katayama I, Kumanogoh A, Tanaka T. Psoriatic arthritis in two patients with an inadequate response to treatment with tocilizumab. Joint Bone Spine. 2012;79:85–7. CrossRefPubMed
34.
Zurück zum Zitat Atzeni F, Ventura D, Batticciotto A, Boccassini L, Sarzi-Puttini P. Interleukin 6 blockade: tocilizumab in psoriatic arthritis. J Rheumatol. 2012;39:97–9. Atzeni F, Ventura D, Batticciotto A, Boccassini L, Sarzi-Puttini P. Interleukin 6 blockade: tocilizumab in psoriatic arthritis. J Rheumatol. 2012;39:97–9.
35.
Zurück zum Zitat Suzuki H, Yasukawa K, Saito T, Narazaki M, Hasegawa A, Taga T, Kishimoto T. Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. Eur J Immunol. 1993;23:1078–82. CrossRefPubMed Suzuki H, Yasukawa K, Saito T, Narazaki M, Hasegawa A, Taga T, Kishimoto T. Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. Eur J Immunol. 1993;23:1078–82. CrossRefPubMed
36.
Zurück zum Zitat Tang B, Matsuda T, Akira S, Nagata N, Ikehara S, Hirano T, Kishimoto T. Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol. 1991;3:273–8. CrossRefPubMed Tang B, Matsuda T, Akira S, Nagata N, Ikehara S, Hirano T, Kishimoto T. Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol. 1991;3:273–8. CrossRefPubMed
38.
Zurück zum Zitat Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007;27:461–6. CrossRefPubMed Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007;27:461–6. CrossRefPubMed
39.
Zurück zum Zitat Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol. 1991;147:117–23. PubMed Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol. 1991;147:117–23. PubMed
40.
Zurück zum Zitat Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010;62:542–52. CrossRefPubMedCentralPubMed Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010;62:542–52. CrossRefPubMedCentralPubMed
41.
Zurück zum Zitat Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S, Borghaei H, Jagannath S, Sokol L, Usmani SZ, et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res. 2013;19:3659–70. CrossRefPubMed Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S, Borghaei H, Jagannath S, Sokol L, Usmani SZ, et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res. 2013;19:3659–70. CrossRefPubMed
42.
Zurück zum Zitat Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959–64. CrossRefPubMed Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959–64. CrossRefPubMed
43.
Zurück zum Zitat de Benedetti F, Massa M, Robbioni P, Ravelli A, Burgio GR, Martini A. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum. 1991;34:1158–63. CrossRefPubMed de Benedetti F, Massa M, Robbioni P, Ravelli A, Burgio GR, Martini A. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum. 1991;34:1158–63. CrossRefPubMed
44.
Zurück zum Zitat Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med. 1994;121:484–91. CrossRefPubMed Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med. 1994;121:484–91. CrossRefPubMed
45.
Zurück zum Zitat Roche NE, Fulbright JW, Wagner AD, Hunder GG, Goronzy JJ, Weyand CM. Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum. 1993;36:1286–94. CrossRefPubMed Roche NE, Fulbright JW, Wagner AD, Hunder GG, Goronzy JJ, Weyand CM. Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum. 1993;36:1286–94. CrossRefPubMed
46.
Zurück zum Zitat Beyer C, Axmann R, Sahinbegovic E, Distler JH, Manger B, Schett G, Zwerina J. Anti-interleukin 6 receptor therapy as rescue treatment for giant cell arteritis. Ann Rheum Dis. 2011;70:1874–5. CrossRefPubMed Beyer C, Axmann R, Sahinbegovic E, Distler JH, Manger B, Schett G, Zwerina J. Anti-interleukin 6 receptor therapy as rescue treatment for giant cell arteritis. Ann Rheum Dis. 2011;70:1874–5. CrossRefPubMed
47.
Zurück zum Zitat Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012;64:1720–9. CrossRefPubMed Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012;64:1720–9. CrossRefPubMed
48.
Zurück zum Zitat Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T. Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum. 2008;58:1197–1200. CrossRefPubMed Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T. Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum. 2008;58:1197–1200. CrossRefPubMed
49.
Zurück zum Zitat de Boysson H, Fevrier J, Nicolle A, Auzary C, Geffray L. Tocilizumab in the treatment of the adult-onset Still’s disease: current clinical evidence. Clin Rheumatol. 2013;32:141–7. CrossRefPubMed de Boysson H, Fevrier J, Nicolle A, Auzary C, Geffray L. Tocilizumab in the treatment of the adult-onset Still’s disease: current clinical evidence. Clin Rheumatol. 2013;32:141–7. CrossRefPubMed
Metadaten
Titel
IL-6 blockade in chronic inflammatory diseases
verfasst von
MD Antonia Puchner
MD Stephan Blüml
Publikationsdatum
01.01.2015
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 1-2/2015
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-014-0321-x