Why is the safety profile of Adacolumn® classified as excellent?

Dr. Daniel Ginard

The safety profile of Adacolumn® is excellent because it’s not a drug. It is a device, a procedure where we capture pro-inflammatory cells, activated granulocytes and cytokines, but we do not use a drug, we are simply trapping a type of activated inflammatory cell. So the safety profile is very good because there are no side effects from any drug and the side effects we do see are usually either associated with the venous access or mild side effects, such as a headache during the process.

When we looked at different studies, we saw that it has a high safety profile, that there are not more side effects than in the group that does not undergo the treatment (control group) and that also when we look at it by age, we see that patients over 65 years of age have the same side effects as patients under 65 years of age, which are minimal, so it has a high safety profile.

References:

• Adacolumn® Instructions for use.
• Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y et al.: Treating ulcerative colitis by Adacolumn therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan Dig Liver Dis. 2009 Aug;41(8):570-7.
• Chen XL Jing-Wei Mao, and Ying-De Wang Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future, World J Gastrointest Pathophysiol. 2020 May 12; 11(3): 43–56.
• Vecchi M, Vernia P, Riegler G et al. Therapeutic landscape for ulcerative colitis: where is the Adacolumn system and where should it be?, Clin Exp Gastroenterol. 2013;6:1-7.
• Saniabadi AR, Hanai H, Takeuchi K, et al.: Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59.

Dr. Eugeni Domènech

The safety profile of GMA has been considered as excellent because of the lack of an association of GMA to other two common adverse events associated to immunosuppressive therapies mainly opportunistic or serious infections and also some tumors. This is this way because although GMA decreases the number of activated neutrophiles, it doesn’t decrease the total number of neutrophils in the bloodstream of the patients. Because those activated neutrophils that are removed from the bloodstream are replaced from the bone marrow pool by young neutrophiles. So the most frequent adverse events with GMA are headache, malaise or some problems with the proceeding itself by the return of filtered venous blood.

References:

• Instructions for use of Adacolumn®.
  • 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. 
  • Sakuraba A et al. An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol. 2009 Dec;104(12):2990-5. 19724269.
  • Hanai H et al. Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol. 2003 Jan;1(1):28-35. 
  • Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y et al.: Treating ulcerative colitis by Adacolumn® therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan Dig Liver Dis. 2009 Aug;41(8):570-7.
  • Vecchi M, Vernia P, Riegler G et al. Therapeutic landscape for ulcerative colitis: where is the Adacolumn® system and where should it be?, Clin Exp Gastroenterol. 2013;6:1-7.
  • Saniabadi AR, Hanai H, Takeuchi K, et al.: Adacolumn®, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59

Dra. Pilar Nós

Adacolumn’s safety profile has been classified as excellent, practically since it was first marketed, which in Europe was in 1999, so we now have more than 20 years of experience with it. We know that it does not increase the risk of infections, that it does not increase the risk of tumours, that it can be administered as therapy and that the side effects, which have been widely reported in the literature, are mild, trivial and may be related to the puncture site, for example, headache, rash, low-grade fever. But of course, the safety profile is a big strength of granulocyte-monocyte apheresis, because it can be used in a fragile population, in the elderly, in children, in people with a history of tumours. And that makes it very safe.

References:

• Adacolumn® instructions for use.
  • 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.
  • Chen XL Jing-Wei Mao, and Ying-De Wang Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future, World J Gastrointest Pathophysiol. 2020 May 12; 11(3): 43–56.
  • Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y et al.: Treating ulcerative colitis by Adacolumn® therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan Dig Liver Dis. 2009 Aug;41(8):570-7.
  • 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.

Dr. Iago Rodríguez Lago

The safety of apheresis is, in my opinion, one of the main strengths of this therapy, and this is because it has a beneficial effect on a flare, but it has no significant immunosuppressive effect on the patient. And this means that these patients are not prone to more infections or any other adverse events. And regarding the tolerance of the therapy from the patients, I must say that patients usually are very happy with this therapy, they tolerate the sessions very well, even if we are with gastrointestinal symptoms. It can be difficult sometimes to tolerate during the sessions, but they are not usually limiting the therapy or the sessions.

If we are seeing the different evidence from randomized controlled trials or the observational studies, we see that randomized controlled trials, they have usually higher adverse event rates. This is because they describe any event that has been reported during the therapy, but they are usually not really related to the therapy, or it can be considered a very relevant event, so they’re usually very overreported, let’s say. But in our practice, these patients usually tolerate the therapy very well. The most frequent adverse event is headache and it can be prevented by the highest rotation and very well tolerance of the patient after the therapy. This is our take home message because usually patients are very worried about the therapy because it’s very different from what they are used to. But once they are receiving the first sessions, I have to say they’re really very happy with the therapy and they have no major concerns about the tolerance. And this is also our evidence because we described recently a survey among patients in Spain and we saw that usually patients are very happy after the therapy and they are even prone to receive another apheresis therapy because they are not afraid of the safety concerns that can be with other therapies.

References:

• Instructions for use of Adacolumn®
• Cabriada, J.L., Rodríguez-Lago, I. Granulocitoaféresis en 2017. Puesta al día. Enfermedad Inflamatoria Intestinal 2017 (16) 2, 62-69.
• Rodríguez-Lago I, Benítez JM, García-Sánchez V, et al. Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients’ point of view. Gastroenterol Hepatol. Aug-Sep 2018;41(7):423-431.
• Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y et al.: Treating ulcerative colitis by Adacolumn® therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan Dig Liver Dis. 2009 Aug;41(8):570-7.
• 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.
• Chen XL Jing-Wei Mao, and Ying-De Wang Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future, World J Gastrointest Pathophysiol. 2020 May 12; 11(3): 43–56.
• Vecchi M, Vernia P, Riegler G et al. Therapeutic landscape for ulcerative colitis: where is the Adacolumn® system and where should it be? Clin Exp Gastroenterol. 2013;6:1-7.
• Saniabadi AR, Hanai H, Takeuchi K, et al.: Adacolumn®, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59.
• 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. Natalia Borruel

Adacolumn® has an excellent safety profile because it’s a treatment that doesn’t increase adverse effects, except for adverse effects purely related to venipuncture. It does not induce immunosuppression, there are no other significant adverse effects. The patients tolerate the apheresis sessions very well. The adverse effects are minimal. The patient may notice a certain amount of dizziness or a bit of discomfort from the venipunctures, but nothing else compared to the adverse events of the drugs we use in inflammatory bowel disease. The patients in whom we use Adacolumn® are often under multiple treatments, they are patients who are taking steroids as well as taking, for example, a biological drug or another drug to induce remission, and it’s very important we don’t add any additional adverse effects. In this regard, Adacolumn® offers us a lot of safety.

References:

• Instrucciones de uso de Adacolumn®
  • 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.
  • Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y et al.: Treating ulcerative colitis by Adacolumn® therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan Dig Liver Dis. 2009 Aug;41(8):570-7.