Dose‐range and dose‐frequency study of recombinant human interleukin‐1 receptor antagonist in patients with rheumatoid arthritis

Campion, G.; Lebsack, M. E.; Lookabaugh, Janice L.; Gordon, Gary V.; Catalano, Michael A.

doi:10.1002/art.1780390704

Cited by 240 publications

(125 citation statements)

References 21 publications

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“…15,17 The efficacy of recombinant human IL-1Ra in the treatment of active RA was confirmed in long-term placebo-controlled clinical studies. 11,12 Recently, recombinant human IL-1Ra protein was approved for the treatment of active RA. However, because of the chronic characteristics of autoimmune arthritis, daily subcutaneous injection of 100 mg IL-1Ra is generally required to obtain a clinically significant benefit.…”

Section: Discussionmentioning

confidence: 99%

“…1,[6][7][8][9][10] Several independent clinical trials have been completed in which the recombinant IL-1Ra protein has been administered for a long-term period to patients with RA. 11,12 The results indicate that treatment with IL-1Ra lowers the levels of proteins involved in the acute phase of RA and the counts of swollen joints and, furthermore, may inhibit radiographic progression of the disease. 12,13 Recently, the use of recombinant human IL-1Ra protein was approved for the treatment of human RA.…”

Section: Introductionmentioning

confidence: 97%

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Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Jeong

et al. 2003

Gene Ther

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The interleukin-1 receptor antagonist (IL-1Ra) is an endogenous protein that can prevent the binding of IL-1 to its cellsurface receptors. Among a number of techniques for gene transfer in vivo, the direct injection of naked DNA into muscle is simple, inexpensive and safe. In this study, we evaluated the potential of intramuscular gene therapy with plasmid DNA containing the cDNA for IL-1Ra in the prevention of murine collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type II collagen. At 4 weeks after the initial immunization, expression plasmid for IL-1Ra was injected into four selected sites in the thigh and calf muscles of DBA/1 mice. Control mice received the same plasmid, but lacking the IL-1Ra coding sequence. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate to severe CIA in the paws of mice injected with IL-1Ra DNA was significantly prevented (Po0.05). In addition, both the synovitis and the cartilage erosion in knee joints were dramatically reduced in mice treated with IL-1Ra DNA (Po0.05). The expression of IL-1b was significantly decreased in the ankle joints of mice treated with IL-1Ra (Po0.01). Interestingly, the levels of IL-1Ra in sera and joints after intramuscular injection of IL-1Ra DNA were significantly lower than when protein had been used in previous reports, suggesting that the therapeutic effect may be achieved by an alternative mechanism(s) rather than by systemic elevation of IL-1Ra. These observations provide the first evidence that direct intramuscular injection of expression plasmid for IL-1Ra may effectively suppress the inflammatory pathology in arthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Jeong

et al. 2003

Gene Ther

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“…Although IL-1 and TNF␣ share many biologic actions that are relevant in RA (4)(5)(6), research in animal models of arthritis suggests that IL-1 is the dominant cartilagedestructive cytokine (7). The biologic effects of both cytokines are modulated in vivo by naturally occurring protein inhibitors (8,9), and both have become prime targets for biologic therapy in RA (10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

“…Following the demonstration of short-term efficacy and safety in a preliminary double-blind, doseranging study in patients with RA (15), the safety and efficacy of daily SC injections of anakinra was confirmed in a large, multicenter, placebo-controlled, 24-week study (16). In addition to demonstrating significant improvements in the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) composite index (22) and the Paulus 20% criteria (23), this study also provided evidence of retardation in the rate of radiographically observed structural damage (16,24).…”

mentioning

confidence: 99%

Long‐term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin‐1 receptor antagonist) in patients with rheumatoid arthritis: Extension phase of a randomized, double‐blind, placebo‐controlled trial

Nuki¹,

Bresnihan²,

Bear³

et al. 2002

Arthritis & Rheumatism

199

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Objective. To demonstrate the long-term efficacy of anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of anakinra at different daily doses.Methods. The efficacy and safety of anakinra were previously demonstrated in a double-blind, placebocontrolled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebocontrolled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure).Results. A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended anakinra therapy.Conclusion. The clinical benefits of treatment with daily self-administered subcutaneous injections of anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of anakinra for the treatment of patients with RA.

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“…[1][2][3][4] Rheumatoid arthritis (RA) is a systemic autoimmune disOne difficulty with using proteins as therapeutic ease characterized by chronic inflammation of the joints. agents for RA is the inability to deliver the protein to the The onset of RA is insidious, but its course is progressive.…”

Section: Introductionmentioning

confidence: 99%

Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy

et al. 1997

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Dose‐range and dose‐frequency study of recombinant human interleukin‐1 receptor antagonist in patients with rheumatoid arthritis

Cited by 240 publications

References 21 publications

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Long‐term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin‐1 receptor antagonist) in patients with rheumatoid arthritis: Extension phase of a randomized, double‐blind, placebo‐controlled trial

Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy

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