Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Attachment, parenting, and separation--individuation in adolescence: a comparison of hospitalized adolescents, institutionalized delinquents, and controls.

The authors compared parent-related perceptions by hospitalized adolescents (i.e., who were admitted to a specialized psychiatric unit; n = 50) and delinquent adolescents (i.e., who were placed at a juvenile treatment institution; n = 51) with adolescents from the general population (n = 51). All adolescents completed a broad set of measures of attachment, perceived parenting, and separation-individuation. Contrary to initial expectations, hospitalized adolescents scored higher than controls on indices of excessive autonomy. Ambivalence regarding issues of interpersonal closeness and distance was found among delinquent adolescents. In addition, hospitalized and delinquent adolescents were found to be struggling, each in their specific way, with attachment-related experiences of trauma. Finally, delinquent adolescents also showed a stage-appropriate form of potentially adaptive narcissism. These findings add to the growing consensus in the literature that associations between adolescent psychopathology and parent-related perceptions are typically complex and somewhat counterintuitive.

Case study: diagnosis and treatment of pyoderma gangrenosum.

Pyoderma gangrenosum, is an ulcerative, inflammatory disorder often associated in the field of stoma care with inflammatory bowel disease (IBD) (Lyon and Smith, 2001). Pyoderma gangrenosum is distinctive in that it normally has a purple rolled edge and is extremely painful. The pathogenesis is unknown but immunologic aberrations of neutrophil granulocytes seem to be important (Petering et al, 2001). This paper demonstrates the rapid development and effective multi-disciplinary team management of an extensive case of Pyoderma gangrenosum. It also explores the possible causes of this particular manifestation.