Biologic agents for rheumatoid arthritis: Can we hypothesize new strategies of treatment?

Rheumatoid arthritis is a complex multifactorial disease, whose pathogenesis has not been fully elucidated. Biologic agents have revolutionized RA treatment, but a significant percentage of patients does not obtain an adequate response to the therapy. Most of the biologic agents do better if combined with conventional immunosuppressive DMARDs and they show a similar efficacy profile: most of the responders achieve the minimum desirable level of response (ACR20) and only few patients obtain a worthwhile clinical improvement (ACR70 or better). We need to identify new strategies of treatment, able to comply the non satisfied needs of RA patients. Taking inspiration from other medical fields, we could hypothesize a combined regimen in which biologic agents are administered simultaneously at a low or ultra-low dosage, targeting several pathogenetic mechanisms but avoiding important side effects. Alternatively it should be useful to identify rapid succession regimens in which biologic drugs are taken according to an established sequence. Research in this field is obviously not encouraged by pharmaceutical industries, but our efforts should be driven in this direction. According to these observations, adequate clinical trials should be designed to search for appropriate drugs associations and dosages.