Marion Thomas ¹, Olivier Fogel ¹, Omar Al Tabaa ¹, Alice Combier ¹, Sandrine Ninino ², Patricia Detre ², Yannick Allanore ¹, Jérôme Avouac ³

Joint Bone Spine. 2024 Dec;91(6):105781. doi: 10.1016/j.jbspin.2024.105781. Epub 2024 Sep 24.

Mariko Seishima 1, Hideki Hachiken 1, Takuma Furukawa 1, Junichiro Yamamoto, Ther Apher Dial. 2024 Mar 12. doi: 10.1111/1744-9987.14118

Introduction: Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly for refractory skin diseases, such as generalized pustular psoriasis and psoriatic arthritis (PsA).

Methods: Four patients with PsA who were refractory to previous treatments were enrolled. They received five or ten sessions of GMA. We assessed the clinical conditions of each patient and laboratory findings before and after GMA.

Results: GMA was effective in plaque-type skin eruptions in all four patients with PsA. It was also effective in joint symptoms in three patients with PsA with mild symptoms, but was ineffective in one patient with severe joint symptoms.

Conclusion: GMA may be recommended to PsA patients with skin eruptions and mild joint symptoms.

Ryosuke Kasuga ¹, Po-Sung Chu ¹, Nobuhito Taniki ¹, Aya Yoshida ¹, Rei Morikawa ¹, Takaya Tabuchi ¹, Fumie Noguchi ¹, Karin Yamataka ¹, Yukie Nakadai ¹, Mayuko Kondo ¹, Hirotoshi Ebinuma ^1 2, Takanori Kanai ¹, Nobuhiro Nakamoto ¹

Hepatol Commun. 2024 Jan 29;8(2):e0371. doi: 10.1097/HC9.0000000000000371. eCollection 2024 Feb 1.

Background: Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.

Methods: This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.

Results: 13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62).

Conclusions: Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).

Ryosuke Kasuga 1, Po-Sung Chu 1, Nobuhito Taniki 1, Aya Yoshida 1, Rei Morikawa 1, Takaya Tabuchi 1, Fumie Noguchi 1, Karin Yamataka 1, Yukie Nakadai 1, Mayuko Kondo 1, Hirotoshi Ebinuma 1 2, Takanori Kanai 1, Nobuhiro Nakamoto 1

Background: Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.

Methods: This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.

Results: 13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62). Conclusions: Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).

F Kenta, S Kensuke, T Shun, W Ryosuke, N Yusuke, Y Ren, S Kentaro, S Itsuki, O Hisashi, M Takuto
Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1807, doi.org=10.1093/ecco-jcc/jjad212.1126

Background
Granulocyte and Monocyte Adsorption Apheresis (GMA) is one of the valuable non-immunosuppressive therapies in the treatment of ulcerative colitis (UC). However, due to the limited number of facilities where GMA can be performed, there are few reports on the combined effects of GMA and prednisolone (PSL), the frequency of GMA implementation or predictive factors for the effectiveness. In this study, we examined the combined effect of GMA and PSL as a remission induction therapy, the frequency of GMA and predictive factors.

Methods
A retrospective observational study was conducted at Kushiro Rosai Hospital. We analyzed clinical data from UC patients who underwent GMA from February 2015 to May 2023.

Results
The study included 54 patients (30 males and 24 females), with a median age of 48 years and a median disease duration of 2 years. The median Lichtiger-CAI (L-CAI) was 8. There were 43 patients of pancolitis. There were 51 biologics-naïve patients and 3 biologics-experienced patients. Concomitant medications included 5-ASA agents in 21 patients, immunomodulators in 7 patients, and PSL in 31 patients. The median CRP was 1.19 mg/dl and the median albumin was 3.5 g/dl. Adverse events were observed in 3 patients (fatigue, dizziness, palpitations). The median number of GMA sessions was 10, with 33 patients undergoing twice weekly and 9 patients three times weekly. The clinical remission rate was 80% (43/54), and the clinical response rate was 89% (48/54), with a significant improvement in the median L-CAI from 8 to 3 before and after GMA (P<0.001). In the comparison between the PSL concomitant group and the non-PSL group, the clinical remission rate was 83.9% (26/31) in PSL group and 73.9% (17/23) in non-PSLgroup (P=0.369). The clinical response rate was significantly higher in the PSL group (87% (27/31)) than in non-PSL group (52.2% (12/23)) (P=0.004). There was no significant difference in the clinical remission/response rate between the group that underwent GMA twice a week (76.9% (30/39)/84.6% (33/39)) and three times a week (77.8% (7/9)/77.8% (7/9)). In univariate analysis, biologics-naïve was extracted as a contributing factor to clinical remission. The cumulative remission rate at 52 weeks was 72% overall. There was no significant difference in the cumulative remission rate between the PSL group (76.8%) and the non-PSL group (67.6%) (P=0.524). There was also no significant difference between the twice-weekly group (75%) and the three-times-weekly group (57.1%) (P=0.236). Conclusion GMA for UC was found to be useful and safely performed as a remission induction therapy. Concomitant use of PSL increased the clinical response rate. The frequency of GMA showed that three times per week was as effective as two times per week.

I Rodríguez-Lago, C Herrera-deGuise, M Boscá-Watts, C Rodríguez, E Leo, M Calvo, F Cañete, S Chacón, C Cuarán, A Elorza, E Guerra, E Iglesias, D Sánchez, M Barreiro-de Acosta, D Ginard, J L Cabriada Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1135, doi.org=10.1093/ecco-jcc/jjad212.0712

Background
Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics, mainly with anti-TNF.

Methods
The aim of our study was to evaluate the clinical efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. A retrospective, multicentric study was performed in 12 IBD Units, including all patients with refractory UC who received combined GMA plus UST. The number of GMA sessions, its frequency, filtered blood volume and time of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing the GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding UST intensification, need for new immunomodulators/biologics and surgery were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results
Nineteen patients were included (15 UC, 2 Crohn’s disease, 2 unclassified IBD; median age 48 years (IQR, 36-63); 68% male). At baseline, 78% were receiving steroids and 23% immunomodulators. Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab. Baseline Mayo score was 6.5 (IQR, 5-7), with a median CRP of 9 mg/L (IQR, 4.8-20.8) and faecal calprotectin 1,612 mg/kg (IQR, 873-4,152). GMA was started mostly after PNR in 83%, the median number of GMA sessions was 16 (IQR, 11-27) and 50% of patients started maintenance GMA. Partial Mayo score significantly decreased 6 months after the last GMA session (p=0.019). During follow-up, 27% started a new biologic therapy and 13% required surgery. 64% of patients under steroids at baseline were able to stop them. Adverse events were reported in 5% of patients.

Conclusion
GMA can safely recapture the response to UST in refractory patients after PNR or LOR to this drug.

Iago Rodríguez-Lago 1, Fiorella Cañete 2, Elena Guerra-Del-Río 3, Claudia Herrera-deGuise 4, Eva Iglesias 5, Eduardo Leo 6, Yamile Zabana 7, Manuel Barreiro-de Acosta 8, Daniel Ginard 9, José Luis Cabriada 10
Gastroenterol Hepatol. 2024 Jan 23:S0210-5705(24)00022-0. doi: 10.1016/j.gastrohep.2024.01.004. Online ahead of print.
[Article in English, Spanish]

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC.

Patients and methods: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. Conclusion: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug

E Papathanasiou , P Markopoulos , M Tzouvala , A Ioannou , E Tsironi , E Zacharopoulou , M Tzakri , E Pantelakis , G Leonidakis , G Bamias , S Michopoulos , E Zampeli

Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i1356–i1357, https://doi.org/10.1093/ecco-jcc/jjad212.0857

Background: Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ^® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients. Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis.

Methods: Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ^® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA.

Results: Ten patients with refractory UC were offered Adacolumn^® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study.

Conclusion

1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients.

2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA.

This observation may help define a subset of UC patients who may benefit the most.

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Satoshi Tanida 1 2, Ryoji Kubo 3, Shoichiro Yoshii 3, Takuya Takahama 2, Shun Sasoh 2, Yoshimasa Kubota 2, Tesshin Ban 2, Tomoaki Ando 2, Makoto Nakamura 2, Takashi Joh 2 Case Reports J Clin Med Res . 2023 Dec;15(10-11):446-455. doi: 10.14740/jocmr5005. Epub 2023 Nov 3.

A 44-year-old woman who had been diagnosed with ulcerative colitis (UC) at 22 years old was diagnosed with severe flare-up of UC based on endoscopic findings associated with new-onset active pyoderma gangrenosum (PG) on both lower legs after she decided to discontinue UC treatment. Systemic treatment with intravenous prednisolone at 30 mg/day had achieved insufficient response to UC and PG, resulting in a diagnosis of corticosteroid-refractory UC and PG. Combination therapy with upadacitinib at 45 mg/day plus intensive granulocyte and monocyte adsorptive apheresis (GMA) was started to achieve clinical remission of UC. Ten weeks after starting this combination therapy, clinical improvement of UC was achieved with PG ulcer healing on both lower legs. A combination of upadacitinib plus intensive GMA may offer an effective therapeutic option for patients with active PG in addition to UC but has yet to be approved for induction or maintenance treatment of PG worldwide. PG is a dermatological involvement in UC patients that requires attention.