title: Cytotoxic agents in sarcoidosis: which one should we choose?
abstract: OBJECTIVE
  Sarcoidosis is a granulomatous disease which affects multiple organs. Its therapeutic management is very challenging due to the heterogeneity in disease manifestation and clinical course, as well as the potential side effects of the immunosuppressive therapy. An overview of presently available second-line and third-line systemic agents is provided.
  
  
  RESULTS
  Because curative treatment is currently not available for sarcoidosis, nonspecific immunosuppression with prednisone remains the first-choice therapy. However, as chronic use of corticosteroids is accompanied with severe adverse events, timely implementation of appropriate steroid-sparing cytotoxic agents is important. Commonly prescribed second-line agents in sarcoidosis are methotrexate, azathioprine, leflunomide and hydroxychloroquine. Nevertheless, the evidence supporting their use is limited. Third-line treatment options, including tumor necrosis factor-alpha inhibitors infliximab and adalimumab and the experimental therapeutic rituximab, are currently reserved for patients refractory to standard therapy.
  
  
  CONCLUSIONS
  A better insight into the advantages and disadvantages of second-line and third-line treatment is important. The long-term effects of immunosuppressive agents, the optimal starting and maintenance dosages, and the best interval and discontinuation regimens should be elucidated. Identified associations of polymorphisms with treatment response suggest a step towards personalized medicine. Future research should focus on the role for pharmacogenetic and phenotypic predictors of treatment response and toxicity.
authors.affiliation: aCentre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein bild care expertise team, Department of Respiratory Medicine, Hospital Gelderse Vallei, Ede cDepartment of Internal Medicine, Atrium Medical Centre, Heerlen dDivision of Heart and Lungs, University Medical Centre Utrecht, Utrecht eDepartment of Toxicology, Faculty of Health, Medicine and Life Sciences (FHML), University Maastricht, Maastricht, The Netherlands *Adriane D.M. Vorselaars and Johanna P. Cremers contributed equally to the writing of this article.
authors.forename: Adriane D M
authors.initials: AD
authors.lastname: Vorselaars
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Cremers
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
mesh_terms: D003603:Cytotoxins / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D012507:Sarcoidosis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D003603:Cytotoxins; D007166:Immunosuppressive Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha