Serum drug levels of biologic agents in the management of rheumatoid arthritis and spondyloarthritis: a systematic review

  • María Martín-López
  • Loreto Carmona
  • Alejandro Balsa
  • Jaime Calvo-Alén
  • Raimon Sanmartí
  • Jesús Tornero
  • José Rosas
Systematic Review

Abstract

The utility of monitoring drug levels in rheumatoid arthritis and spondyloarthritis patients on biological therapy is called into question. The objective was to study relevant clinical questions on the topic, i.e., (1) whether drug levels predict relapse in patients whose biologic was optimized because of remission or low disease activity; (2) whether information about drug levels influences the prognosis of patients with primary or secondary failure to a biological therapy; and (3) whether methotrexate (MTX) influences the association between drug levels and response. Medline, Embase, Cochrane databases were screened, from inception to December 2016 in search for all studies related to the three research questions about. Overall characteristics and outcomes of the studies were collected in a table of evidence and the quality of the studies was assessed with the Newcastle-Ottawa scale or the GRADEpro. Two studies responded the first question, 5 the second, and 7 the third. Studies were small and with limitations, but suggest that measurement drug levels may be useful in patients in remission; that higher drug levels predict a longer relapse-free optimization, and in patients with failure to a biological agent, treatment may need individual adjustment according to the presence of drug levels or antidrug-antibodies. In addition, MTX influences the association between response and drug levels. Monitoring drug levels would allow optimal use of current biological therapies, but more studies and of better quality are needed to draw definitive conclusions.

Keywords

Rheumatoid arthritis Spondyloarthritis Drug levels TNF-inhibitors Tocilizumab Biologics Therapeutic drug monitoring 

Notes

Author contributions

JCR conceived the project. MML and LC contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript. All authors discussed the results and were involved in the critical review of the final manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare that there is no competing interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

296_2018_4022_MOESM1_ESM.docx (35 kb)
The electronic search strategy (DOCX 35 KB)
296_2018_4022_MOESM2_ESM.docx (16 kb)
Table of excluded studies (DOCX 15 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Servicio de ReumatologíaHospital Universitario 12 de OctubreMadridSpain
  2. 2.Instituto de Salud Musculoesquelética (InMusc)MadridSpain
  3. 3.Hospital Universitario La PazMadridSpain
  4. 4.Hospital Universitario ArabaVitoriaSpain
  5. 5.Hospital Clinic de BarcelonaBarcelonaSpain
  6. 6.Hospital General Universitario de GuadalajaraGuadalajaraSpain
  7. 7.Hospital Marina Baixa, VillajoyosaAlicanteSpain

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