Future use of biologic agents alone and in combination for the treatment of rheumatoid arthritis

Journal/Book: Z Rheumatol 1998; 57: 041 - 045. 1998;

Abstract: V. Strand M. D.; Stanford University School of Medicine San Francisco Introduction Increasingly data supporting the use of biologic agents for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases are more positive and offer real promise for symptom control and possibly disease remission. Although depleting anti CD4 monoclonal antibodies (mAbs) failed to offer benefit one "non-depleting" anti CD4 mAbs is currently in clinical trials and significant short term benefit v. placebo has been demonstrated for another (primatized) anti CD4 mAb (1). TNF( and IL-1( antagonists have been shown to be effective against placebo in trials of one month (chimeric and humanized anti TNF( mAbs) 3 months (soluble TNF( receptors: sTNF-Rp55 and p75) and 6 months (IL-1ra) duration (2 - 7). Products which interfere with the trimolecular complex of major histocompatibility complex II (MHC) - Antigen (Ag) - T cell receptor (TcR) or are Ag specific may offer benefit in RA without causing immunosuppression. To date results with oral collagen have been disappointing; data with MHC blockade are preliminary (8 - 11). Vaccination based on TcR V( peptides has shown promising results in multiple sclerosis and RA (12 13). This therapy is well tolerated and may be of particular value in early disease with second line agents or when followed by treatment with cytokine antagonists. On the horizon are agents designed to interfere with T cell activation and T cell interaction with cognate antigen presenting cells: anti CD40 ligand CTLA4Ig anti B7.1 and B7.2 mAbs; as well as mAb to complement 5 to inhibit complement activation and deposition (14 - 17). Both approaches may offer benefit in SLE as well as RA. Other aggressive treatments under evaluation include autologous stem cell transplantation and gene therapy to introduce cytokine antagonists (IL-1ra sIL-1R sTNF-R) into inflamed synovium (18 - 20). ... le

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