Can Adacolumn® be used in biologic-reponsive patients who just starts to have detectable antidrug-antibodies in the blood to prevent loss of response or drop in blood drug levels? 

Dr. Daniel Ginard

We know that immunogenicity to Anti-TNF agents is one of the major problems with these therapies and we also know that immunogenicity the driver to the loss of response, but also to infusion reactions. This is a concern with these therapies, and we have different strategies to overcome the situation. We know that we can combine immunosuppressive therapy so this can reduce the antidrug antibodies. We can also increase the dose of the Anti-TNF agent, but we now know, at least with some preliminary data, that antidrug antibodies can also be reduced with a combination, at least with Infliximab. So, this is a positive finding because we have more options in this situation and we can combine most suppressive therapies, but also apheresis depending on the patient characteristics. So well, this is very good, but needs to be confirmed in further studies, different populations and situations, but it is positive evidence for us.

References:

• Yoko Yokoyama, Koji Sawada, Nobuo Aoyama, et al: Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab, Journal of Crohn’s and Colitis 2020,1-10.
• Rodríguez-Lago I, et al.: Granulocyte-monocyte apheresis: an alternative combination therapy after Loss of response to anti-TNF agents in ulcerative colitis? Scand J Gastro 2019 Apr;54(4):459-464.
• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.
• Yokoyama Y, Kamikozuru K, Watanabe K, Nakamura S. Inflammatory bowel disease patients experiencing a loss of response to infliximab regain long-term response after undergoing granulocyte/monocyte apheresis: A case series. Cytokine. 2018 Mar;103:25-28.

Dr. Iago Rodríguez Lago

We know that immunogenicity to Anti-TNF agents is the main driver to the loss of response and also to infusion reactions. This is one of the major concerns with Anti-TNF drugs. But we know at least there’s some preliminary evidence that has demonstrated that the combination between the apheresis and Infliximab therapy can reduce, can improve the situation of the Anti-TNF therapy by reducing the antidrug antibodies. This is very good evidence because this is one of the major drivers to the loss of response and the need for further changes on the therapy, so well, we need to still have further evidence, confirmation studies for this preliminary data.

But this is positive because it can to reduce one of the major problems with this therapy.

References:

• Yoko Yokoyama, Koji Sawada, Nobuo Aoyama, et al:  Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab, Journal of Crohn’s and Colitis 2020,1-10.
• Rodríguez-Lago I, et al.: Granulocyte-monocyte apheresis: an alternative combination therapy after Loss of response to anti-TNF agents in ulcerative colitis? Scand J Gastro 2019 Apr;54(4):459-464.
• Iizuka M, Etou T, Sagara S. Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy. World J Gastroenterol. 2022 Sep 14;28(34):4959-4972.
• Bamias G, Zampeli E, Domènech E. Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis. Expert Rev Gastroenterol Hepatol. 2022 Aug;16(8):721-735.
• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.

Dra. Pilar Nos

Apheresis has been used for this and in fact there have been reviews that suggest that using it as a bridge could be a good scenario, for example, as a bridge to maintenance with vedolizumab, with an integrin, this has been suggested. It has also been suggested that it may be used initially in combination and then one of the two mechanisms can be removed. What is true is that we are in absolute scientific limbo because here our experiences are from observational series and it is also very difficult to have factors that predict the response. We don’t have a crystal ball to tell us which patients are going to benefit from the combination, in which patients you have to remove one of the drugs. If we don’t know for things as widespread as an anti-TNF and an immunosuppressant, then we’re in a position where individualisation is all we can do.

References:

• Yoko Yokoyama, Koji Sawada, Nobuo Aoyama, et al:  Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab, Journal of Crohn’s and Colitis 2020,1-10.
• Rodríguez-Lago I, et al.: Granulocyte-monocyte apheresis: an alternative combination therapy after Loss of response to anti-TNF agents in ulcerative colitis? Scand J Gastro 2019 Apr;54(4):459-464.
• Iizuka M, Etou T, Sagara S. Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy. World J Gastroenterol. 2022 Sep 14;28(34):4959-4972.
• Bamias G, Zampeli E, Domènech E. Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis. Expert Rev Gastroenterol Hepatol. 2022 Aug;16(8):721-735.
• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.