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.

Building Veterinarians beyond Veterinary School: Challenges and Opportunities for Continuing Professional Development in Veterinary Medicine.

Continuing professional development (CPD) is an important mechanism for veterinarians to acquire, maintain, and enhance their capability to perform competently in their chosen practice area over their career. Although most licensing bodies require veterinarians to complete a minimum number of CPD hours each registration cycle, there are known issues with verifying that these activities are having the desired effects of ensuring professional competence and improving outcomes for patients, owners, and veterinarians. In this review, we summarize the literature across different health care professions to highlight three key challenges for veterinary CPD programs. These are (a) defining what it means to be professionally competent across different career stages from graduation to retirement, (b) delivering CPD activities that are effective in promoting evidence-based medicine and behavioral change in practice, and (c) developing reliable and sustainable systems to formally assess the continued professional competence of veterinarians. A common theme across all challenges was the importance of interacting with colleagues as an opportunity to receive external feedback on their professional strengths and weaknesses and to develop stronger support networks for managing common stressors in clinical practice. There was also a recognized need to develop more transparent outlines of the available and acceptable options for managing different animal health concerns as a first step toward identifying new opportunities for the veterinary profession to elevate the level of care provided. Based on these findings, we propose a new framework for defining, delivering, and evaluating CPD that promotes stronger collaboration between veterinarians to improve professional and personal well-being.