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Alessandro Armuzzi, Simon Travis, Swallowing anti-TNFα in Ulcerative Colitis: Potentially More Gain Than Pain, Journal of Crohn's and Colitis, Volume 10, Issue 6, June 2016, Pages 629–630, https://doi.org/10.1093/ecco-jcc/jjw043
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The introduction of anti-tumour necrosis factor α (TNFα) monoclonal antibodies in the late 1990s led to major advances in the management of outpatients with symptoms and endoscopic evidence of active ulcerative colitis (UC), despite ongoing treatment with conventional therapy. Infliximab, adalimumab and the more recently introduced golimumab are effective for inducing and maintaining clinical and endoscopic remission in both pivotal trials and practice. 1 Although these drugs are generally well tolerated, serious adverse events can occur because they cause systemic immunosuppression. Anti-TNFα-related safety concerns, such as opportunistic infections, 2 autoimmunity, lymphoma/malignancies 3 , demyelinating disease and congestive heart failure, limit their appeal to some patients. Moreover, a significant proportion of patients lose response over time and the development of immunogenicity, 4 associated with the presence of anti-drug antibodies (ADAs), is an important determinant.
In this issue of the Journal of Crohn’s and Colitis , two companion papers report on the safety, pharmacokinetics, immunogenicity, preliminary efficacy and colonic tissue activity of AVX-470 in patients with active UC. AVX-470 is an oral formulation of polyclonal immunoglobulin (Ig) purified from the colostrum of cows immunized with recombinant human TNF. In the study by Harris et al ., 36 adult patients with moderate to severe active UC were randomized to receive either daily ascending oral doses (0.2, 1.6 or 3.5g/day) of AVX-470 or matching placebo for 4 weeks. The primary endpoint of this first-in-human trial was safety; pharmacokinetics and immunogenicity were assessed as secondary, while efficacy and pharmacodynamics were evaluated as exploratory endpoints. AVX-470 was well tolerated, with similar adverse events experienced across groups. In particular, neither adverse events of special interest nor opportunistic infections and allergic reactions were reported. Although baseline bovine Ig was detected in the serum and stool of some patients, indicative of routine dietary intake of dairy products, patients given AVX-470 did not show any significant increase after exposure. Likewise, a dose-dependent increase in bovine Ig with TNF-binding capacity in stool was observed. AVX-470 did not appear capable of inducing human anti-bovine antibodies (HABAs) and no change in HABA background levels was observed.
