title: Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab.
abstract: Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking.
  
  
  
  To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients.
  
  
  
  The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as 'sero-reversal', elevation of drug levels and regained clinical response were the sought outcomes.
  
  
  
  Twenty-three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero-reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero-reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics.
  
  
  
  In almost half of inflammatory bowel disease patients developing anti-adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico-biological response. However, these observations need to be confirmed with larger studies.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Kopylov
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Engel
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Yavzori
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Fudim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Picard
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Lang
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France.
authors.forename: N
authors.initials: N
authors.lastname: Williet
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France.
authors.forename: S
authors.initials: S
authors.lastname: Paul
authors.affiliation: Rambam Health Care Campus, Bruce & Ruth Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Chowers
authors.affiliation: Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Bar-Gil Shitrit
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Eliakim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France.
authors.forename: X
authors.initials: X
authors.lastname: Roblin
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D001379:Azathioprine / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D007155:Immunologic Factors; D015122:Mercaptopurine; D000068879:Adalimumab; D001379:Azathioprine; D008727:Methotrexate