title: Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.
abstract: BACKGROUND
  We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA).
  
  
  METHODS
  The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria.
  
  
  RESULTS
  An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication.
  
  
  CONCLUSIONS
  Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.
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mesh_terms: D000068879:Adalimumab / Q000235:genetics* / Q000627:therapeutic use; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D005260:Female; D005838:Genotype; D006801:Humans; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G / Q000235:genetics*; D000069285:Infliximab / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab