When used in combination with other drugs, can the drug be retained in the column (especially biologics)? 

Dra. Pilar Nos

There is no evidence of how to use Adacolumn® together with biologics, particularly if they are administered intravenously. Typically, when we have used the combination of biologics with granulocyte-monocyte apheresis in routine clinical practice, we will administer the apheresis with an interval of around two/three days between sessions. If we are doing two apheresis sessions per week, we alternate them with the administration of a biologic which is usually anti-TNF, the most widely used biologic in clinical practice. What we have seen is that the effect it has on drug levels is positive and there are in-vitro studies that show that apheresis is capable of increasing drug levels and also decreasing anti-drug antibody levels, in other words it decreases anti-TNF antibodies. This has been seen for anti-TNF, which enhances synergy because it increases drug levels and lowers anti-drug antibody levels. So, it prevents both primary non-response and loss of response.

References:

• N. Kashiwagi, Mode of Action of Apheresis for IBD: Recent Findings —GCAP: GMA (Granulocyte and Monocyte Adsorptive Apheresis), Japanese J. Apher. 2011; 30(1): 39-47.
• 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.
• 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.

Dr. Iago Rodríguez Lago

Sometimes we consider a combination therapy with apheresis and a biological therapy. There are still many questions open about this situation, but we now know that this combination therapy is safe in our experience and we have experience in Spain, it is safe and it is also beneficial. We can recapture the response to biological therapies if we are combining apheresis. We still don’t know the number of sessions or the ideal combination, I mean, regarding the time between the sessions and the biological therapy also, which is the safest. But we have not seen important safety concerns in this type of therapies. But we still don’t know how this combination completely works. But we know that probably apheresis is reducing the inflammatory burden of these patients and I mean the CRP levels when can come down and this benefits the biological therapy, but also it can produce a reduction in some antidrug antibodies. This is recent evidence from Japan and we have seen that the levels of the drug itself, for example Anti-TNF agents are not reduced when we are combining apheresis sessions. But despite this evidence, we see that the antidrug antibodies can come down after the apheresis. So well, we know that it is safe, we know that it does not influence the drug levels, the trough levels of the biologics. So, this is why we are more and more considering combination therapy between these two, device of apheresis and the biological therapies in our clinical practice.

References:

• N. Kashiwagi, Mode of Action of Apheresis for IBD: Recent Findings —GCAP: GMA (Granulocyte and Monocyte Adsorptive Apheresis), Japanese J. Apher. 2011; 30(1): 39-47.
• 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.
• 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.

Dr. Daniel Ginard

When we use a biological drug together with apheresis, with Adacolumn®, in principle there is no risk of the drug being retained in the column. The mechanism of action is different and it does not trap the drug. That’s why we don’t have to worry. And when apheresis has to be used in relation to the use of the biologics? It’s possible that there won’t be a problem because it is not trapped. We can even use it at the same time, but what we usually do, is use it between two treatment sessions with the biologic drug and we can do all the sessions between the two infusions, for example, of anti-TNF: put the 10 columns in the 7-8 weeks or we can divide them between two periods of treatment with biologic infusion and we could do 5 sessions after one dose of infliximab and 5 after the next one.

There are some authors who start the first dose, the first session of apheresis, one week after treatment with anti-TNF and others who wait up to 3 weeks and conduct 5 sessions between week 3 and week 8, and then 5 more sessions between week 3 and week 8 following the next dose of infliximab.

References:

• N. Kashiwagi, Mode of Action of Apheresis for IBD: Recent Findings —GCAP: GMA (Granulocyte and Monocyte Adsorptive Apheresis), Japanese J. Apher. 30(1): 39-47, 2011.