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. 2002 Nov;61(11):960–967. doi: 10.1136/ard.61.11.960

Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases

D Hallegua 1, M Weisman 1
PMCID: PMC1753951  PMID: 12379516

Abstract

Methods: The National Library of Medicine's PubMed database was searched for articles about pharmaceutical agents that reduce the biological actions of IL1.

Results: Fish oils and corticosteroids were identified as non-selective pharmacological interventions that reduce the activity of IL1, whereas a recombinant human IL1 receptor antagonist (anakinra) and a soluble recombinant type I IL1 receptor act selectively. To date, anakinra is the only selective intervention that has been shown in controlled clinical trials to be effective and well tolerated in the treatment of a specific human disorder, RA. In controlled clinical trials, anakinra provided significant clinical improvement and slowed radiographic disease progression in patients with active RA. Moreover, addition of anakinra to existing methotrexate treatment significantly reduced signs and symptoms of active disease.

Conclusions: The clinical use of anakinra has been demonstrated in the management of RA, but blocking of IL1 in other human disorders, as well as the safety of the use of these blocking agents in chronic diseases, still needs to be defined by controlled clinical investigations.

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Figure 1 .

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IL1Ra blocks IL1 binding and subsequent intracellular signalling.

Figure 2 .

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Effect of IL1Ra on radiographic progression of RA. Serial hand radiographs at baseline and after 24 weeks were evaluated by the Genant method for patients treated with placebo (n=78) or IL1Ra 30 mg (n=86), 75 mg (n=83), or 150 mg (n=79). Statistical significance versus placebo is shown above each histogram. From Jiang Y, Genant HK, Watt I, Cobby M, Bresnihan B, Aitchison R, et al. A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 2000;43:1001–9. Copyright © 2000 Wiley-Liss Inc. Reprinted by permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc.

Figure 3 .

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Effect of combination IL1Ra and methotrexate treatment versus methotrexate alone on ACR 20% response rates after 24 weeks of treatment. From Cohen S, Hurd E, Cush JJ, et al. Treatment with interleukin-1 receptor antagonist in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients [abstract]. Arthritis Rheum 1999;42(suppl):S273. Copyright © 1994 Wiley-Liss Inc. Reprinted by permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc.

Figure 4 .

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Distribution of withdrawals due to adverse events with IL1Ra and placebo in patients with RA. From Bresnihan B, Alvaro-Gracia JM, Cobby M, Doherty M, Domljan Z, Emery P, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 1998;41:2196–204. Copyright © 1998 Wiley-Liss Inc. Reprinted by permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc.

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