Genotypes, phenotypes and treatment with immunomodulators in the rheumatic diseases

J Intern Med. 2018 Sep;284(3):228-239. doi: 10.1111/joim.12800. Epub 2018 Jul 2.


The autoimmune rheumatological diseases rheumatoid arthritis (RA), spondyloarthritis (SpA) and systemic lupus erythematosus (SLE) are treated with conventional immunosuppressive agents and with modern biological immunomodulators. The latter group of medications have brought about a major change in our ability to control RA and SpA, with more modest results for SLE. The biologicals are very specific in their mechanisms of action, targeting one specific cytokine or one particular cellular marker. Because of this, their efficacy can readily be linked to a single immunomodulatory mechanism. This observation has fuelled hopes that the efficacy of these agents can be predicted at the individual level based on the patient's genetic predisposition, immunological profile or disease phenotype. Whilst the biologic therapies have improved the prospects for patients with these diseases very significantly, the hope that they could be targeted to the patient in an individualized manner has not completely born fruit. In this review, I will argue that we are witnessing important progress in this field, and that justified hope exists for true advances in precision medicine in the autoimmune diseases in the coming years.

Keywords: biologicals; genotypes; phenotypes; rheumatoid arthritis; spondyloarthritis; systemic lupus erythematosus; treatment.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • Biological Products / adverse effects
  • Biological Products / therapeutic use
  • Biomarkers / blood
  • Genetic Predisposition to Disease / genetics
  • Genotype*
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / genetics
  • Phenotype*
  • Rheumatic Diseases / diagnosis
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / genetics*
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / genetics
  • Treatment Outcome


  • Biological Products
  • Biomarkers
  • Immunologic Factors