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

Abstract

There are currently no reports on the efficacy and safety of combination therapy with ustekinumab (UST) plus intensive granulocyte and monocyte adsorptive apheresis (GMA) for the treatment of refractory ulcerative colitis (UC). We retrospectively evaluated the 10-week effectiveness of combination therapy with UST plus intensive GMA on refractory UC patients including two corticosteroid (CS)-dependent patients, two CS-refractory patients and one patient with loss of response to tacrolimus. Four patients were administered initial combination therapy of UST (6 mg/kg UST followed by subcutaneous injections of 90 mg UST every 8 weeks) plus intensive GMA. Of the four patients who received this combination therapy, two (50%) achieved clinical remission at 10 weeks. The rate of patients achieving endoscopic improvement (endoscopy subscore ≤ 1) at 10 weeks was 50%. In all cases, CSs were discontinued within 10 weeks. No adverse events were observed. Combination therapy with UST plus intensive GMA is helpful to reduce clinical disease activities in refractory UC patients and appears well tolerated.

Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study

“…The mechanism underlying GMA involves the Adacolumn, which is filled with cellulose acetate (CA) beads, interacting with fragment crystallizable‐gamma receptor (FcγR) expressed at the surface of activated leukocytes and selectively adsorbing granulocytes and monocytes from the systemic circulation 2 . Numerous reports have described the clinical efficacy and safety of GMA in patients with active UC 3‐22 . Previous reports have demonstrated that patients who were most likely to respond to GMA tended to be first attack cases and were steroid‐naïve with short disease duration and low disease activity 9‐14 .…”

“…2 Numerous reports have described the clinical efficacy and safety of GMA in patients with active UC. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Previous reports have demonstrated that patients who were most likely to respond to GMA tended to be first attack cases and were steroid-naïve with short disease duration and low disease activity. [9][10][11][12][13][14] However, GMA has been reported to enable the evaluation of clinical efficacy for refractory UC such as steroid-dependent UC and immunosuppressor (IM)-resistant UC.…”

“…[9][10][11][12][13][14] However, GMA has been reported to enable the evaluation of clinical efficacy for refractory UC such as steroid-dependent UC and immunosuppressor (IM)-resistant UC. 6,15,16 Moreover, recent studies have described the combined efficacy of GMA with biologics 17,20 and tofacitinib 21 in patients with refractory UC. In addition, the combination of GMA with antitumor necrosis factor (TNF) alpha agents has decreased clinical activity and biomarkers even in cases with lost responses to antiTNF-alpha agents.…”

Adsorptive cytapheresis in ulcerative colitis: A non‐pharmacological therapeutic approach revisited

“…Interestingly, adsorptive cytapheresis induces clinical remission and response, and steroid‐free remission in about 40% of patients showing insufficient‐ or loss of response to biologics (Table 2). 40‐44 The association of GMA to the anti‐TNFα adalimumab increased the remission rate from 42% to 63% 40 . Following secondary loss of response to infliximab the combination therapy with AC reduced the circulating levels of anti‐infliximab antibodies, increased the trough levels of the drug, and restored clinical effectiveness in twothirds of patients, even in the absence of dose optimization 42 .…”

“…Following secondary loss of response to infliximab the combination therapy with AC reduced the circulating levels of anti‐infliximab antibodies, increased the trough levels of the drug, and restored clinical effectiveness in twothirds of patients, even in the absence of dose optimization 42 . The association of ustekinumab with GMA proved effective in few patients with refractory UC 41 . Some evidence suggests the efficacy of GMA in association with the anti α4 β7 integrin vedolizumab following loss of response to the drug 44,45 .…”