Autoimmune Disease: Treatment

Abstract

In should be the past decade, there have been significant advances in the treatment of autoimmune diseases. Biologic therapies (BT), which are targeted at cells and molecules involved in the mechanisms of autoimmunity, provided an exciting era of much promise, which resulted in amelioration of morbidity and mortality in these diseases.

The armoury of conventional immunotherapeutic agents, such as corticosteroids, azathioprine (AZA) and methotrexate (MTX), has been progressively improved by the addition of targeted BT, which may possess less toxicity and undesirable side effects. Many researchers are seeking to identify and trial novel immunotherapeutic strategies. Important examples include therapies aimed at influencing immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules and cytokines) which are thought to be important in disease pathogenesis.

On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) has showed exciting outcome when used as a nontargeted treatment for severe and therapy‐refractory autoimmune diseases.

Overall, various immunotherapeutic strategies are used to treat autoimmune diseases; these have included conventional immunosuppressive drugs and targeted biologic agents. Clinical use, mechanism of actions and common side effects are important to understand.

Key Concepts

  • Autoimmunity is an immune response directed against an antigen within the body of the host. Not all autoimmunity is deleterious.
  • Autoimmune disease occurs when autoimmunity results in tissue damage or organ dysfunction.
  • There is emphasis on avoiding chronic corticosteroid therapy wherever possible, but acute treatment with corticosteroids remains essential in acute severe presentations of several autoimmune diseases.
  • Conventional immunosuppressive therapy remains both clinically efficacious and cost‐effective in many autoimmune diseases.
  • Biologic therapies are now well established in the current treatment of several autoimmune diseases. It is likely that currently unknown side effects of biologics will emerge, especially with prolonged uses. Biologic therapies are now recognised to cause secondary immunodeficiency in a minority of patients, for example hypogammaglobulinaemia.
  • Many new targeted biologic therapies with potentially less toxicities are in development, and will emerge into routine clinical practice over the next few years.

Keywords: autoantibodies; autoimmunity; b‐cells; biologic therapy; conventional therapy; cytokine; immunosuppression; monoclonal antibodies; stem cell transplantation; tolerance

Figure 1. Mechanisms of current immunotherapies. BCDT, B‐cell‐depletion therapy; Ag, antigen; Ab, antibody. Influence of immunotherapeutic drugs indicated by bold arrows. Anti‐BLyS acts on BLyS, a B‐lymphocyte survival factor. Costimulatory molecules CD40 and B7 are present on both APC and B cells. For ease of use, the thicker arrows are only indicated for anti‐CD40 and CTLA4‐Ig on APC. Reproduced with permission from Karim et al. 2009 © Oxford University Press.
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Further Reading

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Elkhalifa, Shuayb, Anwar, Siddiq, and Karim, Yousuf(May 2018) Autoimmune Disease: Treatment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001437.pub3]