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

Table 1 Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient response to thiopurine or immunomodulators

Ref.	Study type	Total number of patients included in the study	Number of patients insufficient response to thiopurine or IM	Regimen of CAP	Rate of remission	Rate of steroid- free remission
Cabriada et al[60], 2010	Prospective study	18 (SD)	18	GMA or LCAP (5-10 sessions, 1 session/wk)		55%
Takayama et al[58], 2013	Historical cohort study	90	14	GMA or LCAP (5-10 sessions, 1-2/wk)	49% (total Pts), pre-use of IM had little effects on the response to therapy
Yokoyama et al[42], 2014	Prospective Observation Study	623 (for efficacy assessment)	196	LCAP (5-10 sessions, mean 8.4), intensive LCAP was performed in > 70% of Pts	73% (Pts concomitantly treated with thiopurine), 71% (Pts treated without thiopurine), P = 0.623
Imperiali et al[61], 2017	Prospective multicenter study	33 (SD)	33	GMA (5 sessions, 1 session/wk)		36%
Yamamoto et al[37], 2018	Retrospective study	593	159	GMA (5 sessions, 1 to 5 sessions/wk), 5 or 6 GMA were added in Pts who did not achieve clinical remission	45% (Pts exposed to IM), 48% (Pts unexposed to IM), P = 0.61
Dignass et al[36], 2016	Single-arm, open-label, multicentre trial	86 (SD)	83	GMA (5-10 sessions, 1 session/wk)	40.3%
Ishiguro et al[62], 2020	Multicenter cohort study	102, SD or SR UC Pts were not included	16	GMA (mean number of GMA 9.9 sessions, 1-3 sessions/wk)		56.3% (Pts concomitantly treated with IM), 53.5% (Pts treated without IM), P = 1.00
Iizuka et al[59], 2021	Retrospective study	55 (SD: 33, SR: 21)	12	GMA or LCAP [5-20 sessions (mean 8.8), 1-2 sessions/wk (in principle)]	66.7% (Pts concomitantly treated with thiopurine), 69.1% (all Pts), no significant differences	41.7% (Pts concomitantly treated with thiopurine), 45.5% (all Pts), no significant differences

CAP: Cytapheresis; GMA: Granulocyte and monocyte adsorptive apheresis; LCAP: Leukocytapheresis; IM: Immunomodulators (or immunosuppressants); Pts: Patients; SD: Steroid dependent patients; SR: Steroid refractory patients; Intensive LCAP: Defined as performing ≥ 4 leukocytapheresis treatment within the first 2 wk.

Table 2 Efficacy of cytapheresis in patients with ulcerative colitis showing previous biologics failure

Ref.	Study type	Biologics exposure	Number of patients (total number of patients in the study)	Regimen of CAP	Rate of remission	Rate of steroid-free remission
Cabriada et al[35], 2012	Retrospective study (results of nationwide Spanish registry)	IFX	33 (total: 142 SD)	GMA (95% of the Pts), 1-10 sessions (median 5 sessions)		37% (all Pts), no differences in clinical remission were found among those Pts with previous thiopurine or IFX failure
Dignass et al[36], 2016	Single-arm, open-label, multicentre trial	TNF-α	37 (total: 86 SD)	GMA (5-10 sessions, 1 session/wk)	27.8% (Pts who failed on TNF-α), 40.3% (Pts who failed on immunosuppressants
Yamamoto et al[37], 2018	Retrospective study	(1) IFX; and (2) ADA	(1) 31; and (2) 36 (total: 593)	GMA (5 sessions, 1 to 5 sessions/wk), 5 or 6 GMA were added in Pts who did not achieve clinical remission	31% (Pts exposed to biologics), 48% (Pts unexposed to biologics), P = 0.01

CAP: Cytapheresis; SD: Steroid dependent patients; GMA: Granulocyte and monocyte adsorptive apheresis; Pts: Patients; IFX: Infliximab; TNF-α: Tumor necrosis factor-α; ADA: Adalimumab.

Table 3 Efficacy of combination therapy with cytapheresis and biologics in inflammatory bowel disease patients showing insufficient response or loss of response to biologics

Ref.	Study type	Biologics to which insufficient response or LOR was shown	Number of patients	Methods of combination therapy	Regimen of CAP	Rate of remission	Rate of response	Rate of steroid-free remission	Rate of AE (%)
González Carro et al[38], 2006	Case report	IFX (LOR)	CD 1	IFX + GMA	GMA 1 session/8 wk, 12 mo	100%
Fukunaga et al[39], 2010	Case report	IFX (LOR)	CD 1	IFX + GMA	GMA 1 sessions/wk, 3 consecutive weeks × 3 courses and maintenance therapy	100%			0/1 (0%)
Sono et al[40], 2012	Prospective study	IFX (LOR)	CD 15	IFX + GMA	GMA 1 session/wk, 5 consecutive wk		46.7%; a fall in CDAI by more than 15%
Ozeki et al[41], 2012	Case report	(1) IFX (failure); (2) ADA (failure); (3) Steroid refractory and etc.	(1) CD 1; (2) CD 1; and (3) CD 3	ADA + GMA	GMA 2 sessions/wk, 5 consecutive wk	100%			0/5 (0%)
Yokoyama et al[42], 2014	Prospective observational study	IFX	UC 42	IFX + LCAP	LCAP 5-10 sessions (mean 8.4), intensive LCAP was performed in > 70% of Pts	69.0% (Pts concomitantly treated with IFX)
Yokoyama et al[43], 2018	Case report	IFX (LOR)	UC 2; CD 1	IFX + GMA	GMA 1 session/wk, 3 consecutive wk or more	UC 100%, CD 100%
Scrivo et al[44], 2018	Case report	VDZ (primary nonresponse to VDZ; Previous LOR to IFX; Primary non-response to ADA)	UC 1	VDZ + GMA	GMA 1 session/wk,5 wk			100%	0/1 (0%)
Sáez-González et al[45], 2018	Case report	VDZ (primary nonresponse to VDZ; Primary nonresponse to ADA and IFX)	UC 1	VDZ + GMA	GMA 2 sessions/wk, 5 wk + 14 monthly maintenance sessions			100%
Tanida et al[46], 2018	Retrospective study	(1) IFX (LOR); (2) ADA (LOR); (3) Steroid refractory	(1) CD 1; (2) CD 1; and (3) CD 1	UST + GMA	GMA: 2 sessions/wk, for 5 consecutive wk	100%		50%	0/3 (0%)
Rodríguez-Lago et al[47], 2019	Retrospective multicenter study	Anti-TNF therapy (IFX 23, ADA 18, GLM 6); Primary nonresponse 49%, LOR 51%	UC 47	Anti-TNF therapy + GMA	GMA 1 sessions/wk 45%, 2 sessions/wk 55%; 5-10 sessions 51%, > 10 sessions 19% (median of 10 sessions)		32%	9%	2/47 (4%)
Rodríguez-Lago et al[48], 2019	Retrospective multicentre pilot study	VDZ (primary nonresponse 25%, secondary LOR 75%); All Pts had previously received anti-TNF agents (IFX 88%, ADA 50%, GLM 38%)	UC 8	VDZ + GMA	GMA: 5-38 sessions (median 15), biweekly 75%, weekly 25%; maintenance GMA 75%, monthly 38%, every 2 wk 25%		Partial Mayo score decreased (P = 0.01)	38%	0/8 (0%)
Nakamura et al[49], 2020	Case report	VDZ (primary nonresponse to VDZ; Serious allergy to IFX)	UC 1	VDZ + GMA	semiweekly GMA, 4 wk	100%
Tanida et al[50], 2020	Retrospective study	(1) IFX(LOR); (2) ADA (LOR); (3) Steroid refractory or dependent	(1) UC 2; (2) UC 2; and (3) UC 3	TOF + GMA	GMA: 2 sessions/wk, total 10 sessions			75%	3/7 (43%)
Yokoyama et al[51], 2020	Preliminary study	IFX (LOR)	UC 7; CD 7	IFX + GMA	1 or 2 sessions/wk, for 5 consecutive wk, Pts who did not achieved remission by week 8 underwent another GMA (1 session/wk, 5 consecutive wk)	All IBD 64.3%, UC 42.9%, CD 85.7%			0/14 (0%)

LOR: Loss of response; CAP: Cytapheresis; CD: Crohn’s disease; GMA: Granulocyte and monocyte adsorptive apheresis; UC: Ulcerative colitis; LCAP: Leukocytapheresis; AE: Adverse events; IFX: Infliximab; ADA: Adalimumab; Pts: Patients; VED: Vedolizumab; UST: Ustekinumab; TNF-α: Tumor necrosis factor-α; GLM: Golimumab; TOF: Tofacitinib; Intensive LCAP: Defined as performing ≥ 4 leukocytapheresis within the first 2 wk.