Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor

Abstract

Every-week (ew) adalimumab (ADA) maintenance following induction therapy with a standard induction regimen has recently been approved for use in Japan. The efficacy and safety of combination therapy with ew-ADA maintenance following standard induction regimen plus intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions/week) for the treatment of refractory ulcerative colitis (UC) displaying failure of conventional, biologics and Janus kinase inhibitor have not been evaluated previously. The present retrospective study evaluated the 10-week efficacy of this combination therapy among refractory UC patients. Six patients were given initial ADA combination therapy (ADA at 160 mg in week 0, ADA 80 mg in week 2, and 40 mg in week 4, followed by ew-ADA at 40 mg/week) plus intensive GMA. One patient (16.6%) achieved clinical remission and two patients (33.3%) achieved endoscopic improvement by week 10. After excluding two patients who discontinued treatment, mean full Mayo score (P = 0.14), endoscopic subscore (P = 0.18) and C-reactive protein level (P = 0.27) at 10 weeks were numerically decreased compared with baseline in the remaining four cases, although the differences were not significant. Use of ew-ADA maintenance following standard induction regimen plus intensive GMA appears unlikely to achieve satisfactory induction of clinical remission in UC patients for whom conventional agents, biologics and Janus kinase inhibitors have failed.

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis

“…Moreover, UPA may have a milder adverse event profile compared to pan-JAK inhibitors like tofacitinib [13]. In addition, intensive granulocyte and monocyte adsorptive apheresis (GMA) preformed in two sessions a week with Adacolumn ® (JIMRO, Takasaki, Japan) is also available in Europe and Japan for the treatment of patients with active UC that may or may not be refractory to standard pharmacotherapy, biologics and JAK inhibitors [14,15]. GMA depletes elevated and activated myeloid lineage leucocytes and is associated with a marked downregulation of inflammatory cytokines including IL-1β, IL-6, IL-8, and TNF-α and expression of leukocyterelated adhesion molecules [16,17].…”

Origin and Function of Monocytes in Inflammatory Bowel Disease

“…Recent clinical data have shown promising results in IBD treatment through the combination of Granulocyte-Monocytes Apheresis with certain pharmacological agents. [1][2][3][4] This emerging evidence highlights the potential efficacy of monocytes-based interventions in IBD, despite the absence of well-established therapeutic guidelines. Moreover, extensive basic research has elucidated the pivotal role of monocytes in the pathogenesis and progression of IBD.…”

“…17,18 Throughout the course of IBD, monocytes process a plethora of signals, such as inflammatory mediators and pattern recognition receptors. [1][2][3][4][5][6][7][8][9][10][11] These signals subsequently lead to the release of cytokines, which play a crucial role in regulating tissue damage and repair, as well as various cellular activities, including differentiation, activation, apoptosis, phagocytosis, and immune responses. [12][13][14][15][16][17] Given the central role of monocytes in the pathogenesis of IBD, they have emerged as a focal point in pathological studies aimed at elucidating the onset and progression of the disease.…”

Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis for Ulcerative Colitis Achieved Ulcer Healing for Pyoderma Gangrenosum

“…Intensive granulocyte and monocyte adsorptive apheresis (GMA) is also available in Europe and Japan for the treatment of active UC that may or may not be refractory to standard pharmacotherapies, biologics and JAK inhibitors [22,23].…”