Approach to loss of response to advanced therapies in inflammatory bowel disease

Table 1 Dose optimisation approaches for advanced therapies in inflammatory bowel disease

Ref.	Number	Disease	PNR and/or SLOR	Study design	Intervention	Follow-up	Outcome	Result
Trials: Vedolizumab dose escalation
Loftus et al[66]	32	UC	LOR	Single-arm open label-multicentre	4 weekly 300 mg	28 weeks	Clinical response/clinical remission	53.1% (19% with response prior to escalation)/25.0% (6% in remission prior)
Vermeire et al[67]	57	Crohn’s	LOR	Single-arm open label-multicentre	4 weekly 300 mg	28 weeks	Clinical Response/Clinical Remission	54.4% (39% with response prior to escalation)/22.8% (4% in remission prior)
Vaughn et al[68]	58	Crohn’s or UC	LOR	Retrospective cohort study-multicentre	4-7 weekly 300 mg	15 weeks	Clinical Response	62.0%
Gouynou et al[69]	23	Crohn’s or UC	PNR/LOR	Retrospective cohort study-single centre	NS-increased frequency	9 months	Clinical response	52.2%
Outtier et al[70]	59	Crohn’s or UC	LOR	Prospective observational study-multicentre	4 weekly 300 mg	8 weeks	Clinical response	54.2%
Kolehmainen et al[71]	36	Crohn’s or UC	PNR/LOR	Retrospective cohort study-single centre	NS-increased frequency	12 months	Clinical response	33.3%
Perry et al[23]	24	UC	PNR/Partial Responder	Retrospective cohort study-single centre	4 weekly 300 mg	51 weeks	Clinical response/corticosteroid free remission	41.7%/41.7%
Christensen et al[72]	43	Crohn’s or UC	NS	Prospective cohort study-single centre	4 or 6 weekly 300 mg	26 weeks	Clinical response/clinical remission	58.1%/55.8%
Dreesen et al[74]	16	Crohn’s or UC	NS	Retrospective cohort study-single centre	4 weekly 300 mg	14 weeks (UC), 22 weeks (Crohn’s)	Clinical response	56.3%
Kopylov et al[73]	48	Crohn’s or UC	NS	Retrospective cohort study-multicentre	4 weekly 300 mg	52 weeks	Clinical response	62.5%
Williet et al[75]	15	Crohn’s or UC	PNR	Prospective cohort study-single centre	4 weekly 300 mg	36 weeks	Clinical response	53.8%
Attauabi et al[76]	37	Crohn’s or UC	LOR	Retrospective cohort study-2 centre	4-7 weekly 300 mg	< 70 weeks	Clinical remission	62.2%
Jairath et al[77]	55	UC	PNR	Open label multicentre RCT	4 weekly 300mg or 600 mg	30 weeks	Clinical response/clinical remission	30.9/9.1%
Trials: Ustekinumab frequency
Dalal et al[41]	75	Crohn’s	LOR	Retrospective cohort study-single centre	4 or 6 weekly 90 mg	12 months	Corticosteroid free clinical remission	54.7%
Derikx et al[48]	47	Crohn’s	NS	Retrospective cohort study-single centre	4 or 6 weekly 90 mg	8.9 months	Corticosteroid free remission	29.6%
Bundschuh et al[98]	27	Crohn’s	LOR	Retrospective cohort study	4 or 6 weekly 90 mg	NS	Clinical response	54.5%
Haider et al[100]	15	Crohn’s	PNR	Retrospective cohort study-single centre	4 weekly 90 mg	78 weeks	Clinical response/clinical remission	46.6%/33.3%
Fumery et al[101]	100	Crohn’s	Partial Response/LOR	Retrospective cohort study-single centre	4 weekly 90 mg	2.4 months	Clinical response/clinical remission	61%/31%
Ollech et al[102]	51	Crohn’s	NS	Retrospective cohort study-single centre	4 weekly 90 mg	5.9 months	Clinical remission	27.5%
Dalal et al[96]	157 (Crohn’s: 117, UC: 40)	Crohn’s or UC	Partial Response/LOR	Retrospective cohort study-single centre	4 or 6 weekly 90 mg	12 months	Steroid free clinical remission	Crohn’s 57.3%/UC 52.5%
Rowbotham et al[107]	24	UC	NS	Randomised-withdrawal maintenance study	8 weekly 90 mg	16 weeks	Clinical remission	58.3%
Trials: Ustekinumab reinduction
Sedano et al[109]	15	Crohn’s	Partial Response/LOR	Retrospective cohort study-single centre	IV reinduction	14.9 weeks	Clinical response/clinical remission	66.7%/53.3%
Heron et al[110]	65	Crohn’s	Partial Response/LOR	Retrospective cohort study - multicentre	IV reinduction	14 weeks	Clinical Remission with either biochemical and endoscopic response or remission	31.0%
Bermejo et al[111]	43	Crohn’s	LOR	Retrospective cohort study-multicentre	IV re-induction	16 weeks	Clinical response/clinical remission	52.8%/43.3%
Ten Bokkel et al[112]	29	Crohn’s	LOR	Prospective cohort study-multicentre	IV re-induction	52 weeks	Clinical remission	44.8%
Trials: Ustekinumab increased frequency and/or reinduction
Cohen et al[99]	68	Crohn’s	PNR/Partial Response	Retrospective cohort study-single centre	IV induction + 4 or 6 weekly 90 mg	3-6 months	Clinical response/clinical remission	79.4%/30.9%
Yao et al[114]	128	Crohn’s	Partial Response/LOR	Retrospective cohort study-single centre	4 weekly 90 mg +/- IV Re-induction	3 months	Clinical remission	62.9% Shortening/69.6% re-induction
Hudson et al[113]	18	Crohn’s	SLOR	Retrospective case series-single centre	IV re-induction +/- 4 or 6 weekly 90 mg	4-8 weeks	Clinical remission or response	83.3%
Ramaswamy et al[106]	31	Crohn’s	Partial response/LOR	Retrospective cohort study-single centre	4 weekly 90 mg +/- IV re-induction	12 weeks	Clinical response	64.5%
Chaparro et al[40]	60	Crohn’s	PNR/LOR	Retrospective cohort study-multicentre	4 weekly 90 mg /IV re-induction	NS	Clinical remission	78.3%
Ma et al[115]	24	Crohn’s	LOR	Retrospective cohort study-multicentre	4 or 6 weekly 90 mg +/- IV reinduction	NS	Clinical response	54.2%
Young et al[97]	21	Crohn’s	PNR/LOR/partial response	Retrospective cohort study-single centre	4 or 6 weekly 90 mg +/- IV induction	177 days	Clinical response	52.4%
Johnson et al[103]	229	Crohn’s	PNR/LOR	Retrospective cohort study-multicentre	4 or 6 weekly 90 mg + IV reinduction/IV reinduction	NS	Clinical response	45.9%
Olmedo et al[104]	91	Crohn’s	PNR/LOR	Retrospective cohort study-multicentre	4 or 6 weekly 90 mg + IV reinduction	16 weeks	Steroid free clinical response/Steroid free clinical remission	62.6%/25.3%
Kopylov et al[105]	142	Crohn’s	NS	Retrospective cohort study-multicentre	4 or 6 weekly 90 mg +/- IV induction	16 weeks	Clinical response/clinical remission	51.4%/38.7%
Trials: Tofacitinib dose escalation
Ma et al[51]	71	UC	LOR	Prospective cohort study-multicentre	10 mg BD	NS	Clinical response	54.9%
Honap et al[52]	19	UC	LOR	Retrospective cohort study-multicentre	10 mg BD	NS	Clinical response	47.4%
Sandborn et al[150]	57	UC	LOR	Prospective cohort study-multicentre	10 mg BD	12 months	Clinical response/clinical remission	64.9%/49.1%
Trials: Upadacitinib dose escalation
Sandborn et al[151]	60	Crohn’s	NS (inadequate response)	Phase II placebo controlled RCT	12 mg BD/24 mg BD IR	52 weeks	Clinical remissions	15% 12 mg BD/24 mg BD 39%
Panaccione et al[153]	190	UC	LOR/inadequate response	Prospective cohort study	30 mg ER daily	48 weeks	Clinical remission	27.9%

PNR: Primary non-response; LOR: Loss of response; BD: Twice a day; UC: Ulcerative colitis; ER: Extended release; IR: Immediate release; SLOR: Secondary loss of response.