How do I know that a patient is responding positively to Adacolumn®? How long should I wait?

Dr. Daniel Ginard

The response to any treatment, including Adacolumn®, depends on a range of variables.

The main one is how the patient is.If the patient has a milder or more moderate form, we can wait longer, while in more severe forms, we can wait fewer weeks for the therapy to have an effect.

Under normal conditions, in a patient where we can afford to wait, I think you have to complete at least part of the induction. If we do 2 sessions per week, we should wait at least 3–4 weeks to see if there is a response. Maybe, if there’s no response after 8 sessions of apheresis, if the patient is not well, then we have to look for an alternative.

If we have achieved a response, even if it is a partial response, we have to maintain it, because we have also seen patients who achieve complete response over a longer period. In other words, if there hasn’t been any response, any change in 2-3 weeks, we’ll maybe have to look for an alternative.

We might also have indirect data. We might have a decrease in calprotectin, a decrease in CRP, which indicate that there is the start of an improvement in these patients and that allows us to maintain and complete the induction.

But, if after completing the induction, we haven’t achieved a response, it’s probably time to look for an alternative.

Dr. Francisco Fernández

Assessing the effectiveness of any treatment we use for inflammatory bowel disease is based on a range of parameters. Firstly, the clinical evaluation, what the patient tells us with regard to their symptoms, the lab data we get from the patient, the imaging data, whether it’s from endoscopes or ultrasounds from the intestine. And all these allow us to know if the patient is progressing favourably with respect to their situation prior to the start of treatment. As the induction procedure progresses, in the initial apheresis sessions, we check the patient’s clinical evolution and when the induction cycle is completed, we also evaluate analytically and ultrasonographically if possible, and ideally endoscopically, if the patient’s clinical situation is better than the initial one in order to decide if there has been adequate effectiveness and if we can continue with this treatment or if, on the contrary, we have to choose another type of treatment. When we carry out an induction apheresis cycle, normally, as is also supported in the trials and articles published, we wait for four weeks after the date of the last induction session to carry out the end-of-induction clinical assessment.

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.

Dra. Pilar Nos

The fact is that efficacy is often measured both by how the patient responds in terms of number of stools, presence of blood in the stools, etc., and by using clinical activity indices or surrogate markers, such as calprotectin, especially when there is little evidence from large and/or powerful clinical trials. So, I always say that a patient responds when they manage to have a good quality of life and normalise their levels of calprotectin, haemoglobin, C-reactive protein or any other marker to an acceptable level. It’s true that if that doesn’t happen or, at least, you don’t see a trend towards it happening in the first two weeks when you have already administered four sessions of apheresis, there is no response, it’s unlikely that the patient is going to respond subsequently. If you are seeing their inflammation markers improve and the patient’s signs and symptoms are also improving, you can wait a bit longer and you can maybe do more intensive sessions and continue with two sessions per week if they are tolerated well. Surprisingly, efficacy in steroid-dependent ulcerative colitis can reach response rates of up to 60%, which is a very high figure for a very safe product, in studies that have mainly been carried out in an Asian population, in Japanese or Chinese people.

References:

• Habermalz, B., Sauerland, S. Clinical Effectiveness of Selective Granulocyte, Monocyte Adsorptive Apheresis with the Adacolumn® Device in Ulcerative Colitis. Dig Dis Sci 2010; 55, 1421–1428).
• Sáez-González E, Moret I, Alvarez-Sotomayor D, Díaz-Jaime FC, Cerrillo E, Iborra M, Nos P, Beltrán B. Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease. Dig Dis Sci. 2017 Jun;62(6):1417-1425.
• Ishiguro Y, Ohmori T, Umemura K, Iizuka M. Factors associated with the outcomes in ulcerative colitis patients undergoing granulocyte and monocyte adsorptive apheresis as remission induction therapy: A multicenter cohort study. Ther Apher Dial. 2021 Aug;25(4):502-512.
• 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. Eugeni Domènech

The prediction of the response to GMA is still a controversial issue. In fact, there is no baseline factor, when the patient starts the therapy, that has been associated to the clinical remission at the end of the therapy. Recent study suggested that a reduction in more than 40% of the baseline fecal calprotectin levels can predict clinical remission at the end of the schedule treatment. Also, the schedule is a controversial issue. In fact, it may vary from center to center and even from physician to physician. In our center, we use ten sessions scheduled starting with an intensive regimen of 2 sessions per week during three weeks, and then we follow with 1 session per week during the four weeks. So, a total of ten sessions at the end of which we decide to follow or not to follow therapy. And if the therapy has been efficient or not.

References:

• 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.
• 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. 
• T. Shimoyama,  T. Yamamoto, S. Umegae et al.: Faecal calprotectin level for assessing endoscopic activity and predicting future clinical course in patients with moderately active ulcerative colitis undergoing GMA: a prospective cohort study. BMC Gastroenterol. 2018 Aug 1;18(1):120.

Dr. Iago Rodríguez Lago

It is sometimes difficult to evaluate the response to some of these therapies applied in ulcerative colitis and when we are speaking about medical therapies, we know that around week 14 is when we reassess the patient in clinical parameters or biomarkers and consider and decide if the patient is responding or not to a medical therapy. When we are speaking about apheresis, well, it is different because the device is different and the treatment strategy is very different. We’re speaking about no a medical therapy. This is not a drug, so the mechanism of action is completely different. This means that the apheresis has a mechanism of action that is slow but also progressive. So we can start to see the initial symptoms that are improving, but also the biomarkers around week three. This is usually described with the CRP or the physical protection. But in our practice, what we usually do is to reassess the patient one month after finishing the apheresis, and this means around two months after starting the apheresis sessions during the induction part.

References:

• Habermalz, B., Sauerland, S. Clinical Effectiveness of Selective Granulocyte, Monocyte Adsorptive Apheresis with the Adacolumn® Device in Ulcerative Colitis. Dig Dis Sci 2010; 55, 1421–1428).
• Sáez-González E, Moret I, Alvarez-Sotomayor D, Díaz-Jaime FC, Cerrillo E, Iborra M, Nos P, Beltrán B. Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease. Dig Dis Sci. 2017 Jun;62(6):1417-1425. Ishiguro Y, Ohmori T, Umemura K, Iizuka M. Factors associated with the outcomes in ulcerative colitis patients undergoing granulocyte and monocyte adsorptive apheresis as remission induction therapy: A multicenter cohort study. Ther Apher Dial. 2021 Aug;25(4):502-512.
• 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