title: Appropriateness of Testing for Anti-Tumor Necrosis Factor Agent and Antibody Concentrations, and Interpretation of Results.
abstract: The availability of tests for blood concentrations of anti-tumor necrosis factor (TNF) agents and antibodies against these drugs could improve dose selection for patients with inflammatory bowel disease (IBD). However, there is little consensus on when to test and how to interpret test results. We used the RAND/UCLA Appropriateness Method to determine when these tests are appropriate and how to clinically interpret their results.
  
  
  
  We conducted a systematic literature search in November 2013 to identify observational or experimental studies of the measurement of anti-TNF drug and antibody concentrations in patients with IBD and interpretation of their results. We developed 35 scenarios that assessed the appropriateness of testing and 143 scenarios that addressed clinical strategies in response to test results, and presented the findings to an expert panel. The appropriateness of each scenario was rated before and after an in-person meeting with the panel. Panelists rated the appropriateness of various clinical management options including changing therapy within class, switching out of class, adjusting drug dose or interval, adding or adjusting concomitant immune modulators, and doing nothing for each of 6 permutations of high versus low drug concentrations and high, low, or undetectable antibody concentrations. Disagreement was assessed using a validated index.
  
  
  
  Assessment of anti-TNF drug and antibody concentrations was rated appropriate at the end of induction therapy in primary nonresponders, in secondary nonresponders, at least once during the first year of maintenance therapy, and following a drug holiday. Routine assessment in responders at the end of induction was rated uncertain. In nearly all scenarios, escalation of drug dosing was rated appropriate when drug concentration was low in the absence of antibodies, and switching within class was rated appropriate when antibodies were present. Other recommendations depended on the specific clinical scenario for which the test was obtained.
  
  
  
  Based on the RAND/UCLA Appropriateness Method of analysis, an expert panel recommends testing for drug and antibody concentrations in many clinical scenarios. The appropriate timing and best way to respond to anti-TNF drug and antibody testing for IBD depends on the specific clinical scenario. These recommendations can help guide clinicians to best optimize anti-TNF therapy.
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: gil.melmed@cshs.org.
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.affiliation: Guy's and St. Thomas' Hospitals, London, United Kingdom.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Irving
authors.affiliation: Dalhousie University, Halifax, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jones
authors.affiliation: University of Calgary, Calgary, Canada.
authors.forename: Gilaad G
authors.initials: GG
authors.lastname: Kaplan
authors.affiliation: Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Kozuch
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Velayos
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Leonard
authors.initials: L
authors.lastname: Baidoo
authors.affiliation: Alfred Hospital, Melbourne, Australia.
authors.forename: Miles P
authors.initials: MP
authors.lastname: Sparrow
authors.affiliation: University of British Columbia, Vancouver, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Bressler
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Cheifetz
authors.affiliation: University of Calgary, Calgary, Canada.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Devlin
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Raffals
authors.affiliation: University of California San Diego, San Diego, California; KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Projections Research Inc, Phoenixville, Pennsylvania.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Mould
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Fred
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.affiliation: University of California San Diego, San Diego, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Siegel
mesh_terms: D000906:Antibodies / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000097:blood*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D000906:Antibodies; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
keywords: Crohn’s Disease; Patient Management; Treatment; Ulcerative Colitis