What is your goal when using Adacolumn® in combination with other drugs?

Dr. Eugeni Domènech

When using GMA as an add on therapy as a combination therapy with different immunosuppressive therapies the great advantage of GMA is its excellent safety profile so you, by adding GMA, you may add efficiency but you are not increasing harm to the patient. So, the addition of GMA doesn’t decrease the safety profile for the patient, but it may increase efficacy. So, you can use GMA for those biological therapies that are considered as safer, like Vedolizumab or Ustekinumab. But you can also add GMA to these therapies that are considered with a worse safety profile, like they may be Anti-TNF or even JAK inhibitors.

References:

• 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. 
• 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.
• Rodríguez-Lago I, Benítez JM, Sempere L, Sáez-González E, Barreiro-de Acosta M, de Zárate JO, Cabriada JL. The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis? J Clin Apher. 2019 Dec;34(6):680-685. 
• Tanida S, Ozeki K, Kanno T et al.: Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis. J Clin Med Res. 2021 Nov;13(10-11):510-514.
• Cabriada JL, et al. Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry. J Gastroenterol. 2012 Apr;47(4):359-65.
• M. Shiraki, T. Yamamoto. Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis, World J Gastroenterol. 2012 Nov 7;18(41):5833-8.
• Tanida S, Ozeki K , Mizoshita T et al.: Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis J Clin Med Res, 2020 Jan;12(1):36-40.

Dr. Daniel Ginard

When I use Adacolumn® in combination with vedolizumab, ustekinumab or tofacitinib, the goals are probably the same as when I use it with an anti-TNF, i.e. to get a patient who has lost their response to regain that response. And if possible, a complete response. Possibly the only time this is different is that sometimes, depending on the line of treatment we’re using, we’re already on the last line of treatment. Maybe the goal in that case, more than a complete remission, is sometimes the most complete response we can achieve, because sometimes we can’t get to complete remission. But the goal is always going to be to try.

References:

• Rodríguez-Lago I, Benítez JM, Sempere L, Sáez-González E, Barreiro-de Acosta M, de Zárate JO, Cabriada JL. The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis? J Clin Apher. 2019 Dec;34(6):680-685.
• Tanida S, Ozeki K, Kanno Tet al.: Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis. J Clin Med Res. 2021 Nov;13(10-11):510-514.
• Tanida S, Ozeki K, Mizoshita T, et al. Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis. J Clin Med Res. 2020 Jan;12(1):36-40.
• Nakamura M, Yamamura T, Maeda K. et al. : Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis. Intern Med. 2020 Dec 1;59(23):3009-3014.
• 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

Many new drugs have been included in the treatment strategy of the apheresis colitis patients and we now have available different biological therapies but also immunosuppressive therapies, especially JACK inhibitors like Tofacitinib. And this makes a different scenario than five or ten years ago for UC. And this means that many patients can benefit from these new therapies but we are probably facing similar problems than in previous years. And this means that these patients receiving new therapies that can benefit from Tofacitinib, Vedolizumab, Ustekinumab for the treatment of UC. But some of them, they are still also losing response to these therapies or demonstrating insufficient response to these therapies. And well the apheresis comes here again, and it has demonstrated at least with some cohort studies that it can be beneficial in terms of clinical response and also safety that it is very important in these combination therapies and also with biomarkers. So well, this is still an option with the immunosuppressive and biological therapies and combination therapy with a apheresis plus a biologic or immunosuppressive therapy is an option for our patients now.

References:

• Rodríguez-Lago I, Benítez JM, Sempere L, Sáez-González E, Barreiro-de Acosta M, de Zárate JO, Cabriada JL. The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis? J Clin Apher. 2019 Dec;34(6):680-685.
• 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.
• 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

The therapeutic objective of a combined treatment, and the truth is that we do not have enough experience in any centre, but all the large centres have already used it as a therapy. When it is used together with vedolizumab, the mechanism is probably synergistic because the aim of vedolizumab is to stop the arrival of lymphocytes, leukocytes, to ensure there is no migration to the intestinal inflammatory focus and, on the other hand, with the apheresis you are filtering peripheral blood, so it is theoretically a good combination. Whether you then decide that the drug you maintain is the integrin or you decide that maintenance should be done with apheresis is also very personalised. But, from a mechanistic point of view, this combination makes sense.

References:

• Rodríguez-Lago I, Benítez JM, Sempere L, Sáez-González E, Barreiro-de Acosta M, de Zárate JO, Cabriada JL. The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis? J Clin Apher. 2019 Dec;34(6):680-685.
• 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.

I believe that the combination of Adacolumn with Ustekinumab has been little explored from the outset because Ustekinumab has been one of the drugs, also very safe, but which has most recently been incorporated into the therapeutic arsenal for ulcerative colitis. It’s a combination that should be good due to its inertia because ustekinumab is a proinflammatory interleukin 12-23 inhibitor, and the mechanism of action of apheresis where it traps cells in the cellulose beads and the decrease of activation of the leukocytes that are trapped there, reduces inflammation even further. It has an immunoregulatory effect that may be additive to the effect of the inhibition of an interleukin, such as 12-23. In any case, I think we are on very preliminary ground that we have very little experience of here. I think there is only one retrospective study with a small number of patients with this combination and more studies would be needed, both with ustekinumab in combination and with other biologics to position the role of apheresis exactly.

References:

• Tanida S, Ozeki K, Kanno Tet al.: Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis. J Clin Med Res. 2021 Nov;13(10-11):510-514.
• 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.

In a patient who is being treated with a JAK-inhibitor, such as tofacitinib or more recently upadacitinib or filgotinib, we are already using a molecule that has side effects, it is no longer a harmless molecule. We know that an increase has been described in the risk of phenomena such as embolism, the risk of infections, especially herpetic infections, which are clearly minimal, but it does have these adverse effects. So, it is not a bad combination to use if it is necessary due to the patient’s situation, due to the supposed reduction in inflammatory load that means that lower doses are required of the JAK-inhibitor, tofacitinib, or the JAKinib we use or that it can be removed earlier. If it is a patient with a vascular risk factor, if it is an elderly, multi-pathological patient with a risk of infection and who after the combination we can leave the safer option, which is apheresis as a monotherapy.

References:

• S. Tanida K. Ozeki, T. Mizoshita, Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis J Clin Med Res, 2020 Jan;12(1):36-40.
• 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.