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

Abstract

Preclinical research on animal models of rheumatoid arthritis (RA) is very important for alerting the healthcare and scientific community and pharmaceutical companies of the existence of new or “forgotten” molecules. Most antirheumatics have side-effects when used in higher doses and/or within long-term dosage. Combinatory therapy is expected to have a higher efficacy without increased toxicity. Methotrexate (MTX) has become the main immunosuppressive substance used in the treatment of patients with RA. However, the use of MTX has to be limited due to its toxic manifestations, e.g. abdominal disorder, alopecia, oral ulcers, and cytopenia (Alarcon et al., 1989). Ineffectiveness of treatment can be also observed. In the survey of McKendry and Dale (McKendry & Dale, 1993), due to the risk of treatment, termination was substantiated in 75% of patients with RA taking MTX for 60 months. An adverse drug effect proved to be a more common reason for treatment termination (53%) compared to loss/lack of beneficial effect (22%), other reasons (16%), or lost of follow-up (9%). On the other hand, the therapeutic efficacy of MTX can be increased by combination with other synthetic drugs or inhibitors of TNF-┙ (Smolen et al., 2010). Application of biological therapy (antibodies or soluble receptors of TNF-┙, IL-1 and IL-6) represents a great progress in the therapy of RA. Yet biological treatment is also frequently combined with MTX (Maini et al., 1998; Weinblatt et al., 1999). There are countless possibilities for combinations with MTX. Many substances were neglected when they failed to show good efficacy in monotherapy compared to standard antirheumatics. They would not get a second chance if the expected reduction of clinical parameters (mainly edema of joints) did not materialize, despite the fact that they improved many biochemical disease markers. Our research in the last years was focused on evaluation of new therapeutics for the combinations of the classical immunosuppressive treatment with immunomodulators and compounds affecting reduction/oxidation homeostasis. Development of drugs for the therapy of RA has been very intensive in recent years. Biological therapy targeted on neutralizing the effect of antiinflammatory cytokines, particularly TNF-┙, IL-1 and IL-6, by using antibodies or soluble receptors provided a great progress in RA therapy. However, not even these expensive drugs are able to cure RA