Biologic agents for treating rheumatoid arthritis. Concepts and progress

Moreland, Larry W.; Heck, Louis W.; Koopman, William J.

doi:10.1002/art.1780400302

Cited by 136 publications

(71 citation statements)

References 105 publications

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“…MTX, a folic acid antagonist, has become the predominant immunosuppressive agent used in the treatment of patients with RA (Williams et al, 1985). MTX acts mainly on actively proliferating cells during the S-phase of proliferation, suppresses macrophage function, modulates interleukin-1 (IL-1) and superoxide anion production, and inhibits neutrophil chemotaxis (Moreland et al, 1997). Furthermore, MTX treatment was shown to decrease synovial collagenase gene expression in patients with RA (Genestier et al, 2000).…”

Section: Natural Substances Isolated From Plantsmentioning

confidence: 99%

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

Bauerová¹,

Poništ²,

Nosáľ³

et al. 2012

Rheumatoid Arthritis - Treatment

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Section: Natural Substances Isolated From Plantsmentioning

confidence: 99%

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

Bauerová¹,

Poništ²,

Nosáľ³

et al. 2012

Rheumatoid Arthritis - Treatment

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“…In both diseases, proinflammatory cytokines and chemokines are believed to play a pivotal role in the attraction of leukocytes to the site of inflammation and in the initiation and progression of the inflammatory process. The role of key cytokines in the regulation of disease has been well characterized in experimental models that have been expanded in clinical trails (3)(4)(5)(6)(7)(8)(9). Chemokines play a major role in the massive recruitment of leukocytes at the site of inflammation during inflammatory conditions (for a recent review, see Ref.…”

Section: Targeting the Function Of Ifn-␥-inducible Protein 10mentioning

confidence: 99%

Targeting the Function of IFN-γ-Inducible Protein 10 Suppresses Ongoing Adjuvant Arthritis

Salomon¹,

Netzer²,

Wildbaum³

et al. 2002

The Journal of Immunology

122

115

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IFN-γ-inducible protein 10 (IP-10) is a CXC chemokine that is thought to manifest a proinflammatory role because it stimulates the directional migration of activated T cells, particularly Th1 cells. It is an open question whether this chemokine is also directly involved in T cell polarization. We show here that during the course of adjuvant-induced arthritis the immune system mounts a notable Ab titer against self-IP-10. Upon the administration of naked DNA encoding IP-10, this titer rapidly accelerates to provide protective immunity. Self-specific Ab to IP-10 developed in protected animals, as well as neutralizing Ab to IP-10 that we have generated in rabbits, could inhibit leukocyte migration, alter the in vivo and in vitro Th1/Th2 balance toward low IFN-γ, low TNF-α, high IL-4-producing T cells, and adoptively transfer disease suppression. This not only demonstrates the pivotal role of this chemokine in T cell polarization during experimentally induced arthritis but also suggests a practical way to interfere in the regulation of disease to provide protective immunity. From the basic science perspective, this study challenges the paradigm of in vivo redundancy. After all, we did not neutralize the activity of other chemokines that bind CXCR3 (i.e., macrophage-induced gene and IFN-inducible T cell α chemoattractant) and yet significantly blocked not only adjuvant-induced arthritis but also the in vivo competence to mount delayed-type hypersensitivity.

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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%

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

200

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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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Biologic agents for treating rheumatoid arthritis. Concepts and progress

Cited by 136 publications

References 105 publications

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

Targeting the Function of IFN-γ-Inducible Protein 10 Suppresses Ongoing Adjuvant Arthritis

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

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