Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

Abstract

Ustekinumab is applied to induce clinical remission in patients with Crohn's disease. Granulocyte and monocyte absorptive apheresis depletes activated myeloid lineage leukocytes and has been applied for active Crohn's disease. This study retrospectively examined the efficacy and safety of combining intensive granulocyte and monocyte absorptive apheresis and ustekinumab for remission induction therapy in refractory Crohn's disease. Between June and September 2017, three consecutive cases (two females) with refractory Crohn's disease were treated with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab. Crohn's disease activity index, and simple endoscopic score for Crohn's disease at baseline and 10 weeks were applied as treatment efficacy outcomes. In all three cases, at week 10, clinical remission was achieved, while simple endoscopic score for Crohn's disease reflected no improvement. Thus, combination therapy with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab appeared to represent a safe and effective intervention for inducing clinical remission.

Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis

“…The mean endoscopic subscore was significantly lower at 10 weeks than at baseline. Based on these outcomes, addition of intensive GMA to TOF monotherapy appeared to be effective in inducing mucosal healing [17,18]. An additional study on a large cohort of patients is warranted to verify this finding.…”

“…Furthermore, in patients with active UC, downregulation of the leukocyte adhesion molecule Lselectin and neutrophil adhesion to endothelial cells activated by IL-1β were observed after in vitro exposure of peripheral blood to G-1 beads that composed a main part of Adacolumn [16]. These suggested that the combination therapy worked by drastically downregulating the circulating inflammatory cytokines and the expressions of adhesive molecules on the activated granulocytes, which was an effect of GMA, and by downregulating the local inflammatory cytokines at the microenvironmental sites in the gut mucosa, which was an effect of TOF, thereby, inducing rapid clinical remission [17,18]. In addition, serious adverse side effects have been rare in patients receiving GMA [9,19].…”

Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis

“…Furthermore, an in vitro study observed that the concentration of soluble cell adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in blood samples was significantly reduced after GMs adsorption with acetate beads [ 9 ]. Such findings suggest that the present combination therapy suppressed leukocyte migration by drastically downregulating circulating inflammatory cytokines and expression of leukocyte-related adhesion molecules as an effect of GMA, and by downregulating local inflammatory cytokines at microenvironmental sites in the gut mucosa, as an effect of UST, thereby inducing rapid CR [ 12 , 13 ]. In addition, serious adverse side effects appear rare in patients receiving GMA [ 3 , 14 ].…”

Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy

“…These studies include eight studies evaluating combination therapy with GMA or LCAP and anti-TNF-α (IFX: 6 studies; ADA: 1 study; IFX, ADA, golimumab: 1 study), four studies with GMA and VDZ, one study with GMA and ustekinumab, and one exceptional study with GMA and a pan-JAK inhibitor tofacitinib. Among these 14 studies, seven studies[ 42 , 44 , 45 , 47 - 50 ] examined the efficacy of combination therapies in patients with UC, five studies[ 38 - 41 , 46 ] examined its efficacy for CD patients, and two studies[ 43 , 51 ] examined its efficacy for both UC and CD patients.…”

“…In addition, Motoya et al [ 52 ] showed that the incidence of AEs among elderly patients was similar in all patients. Regarding the safety of the combination therapy with CAP and biologics, eight out of 14 studies listed in Table 3 reported the rate of AEs[ 39 , 41 , 44 , 46 - 48 , 50 , 51 ]. Six of the eight studies reported no adverse events.…”