Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases

Table 1 Currently approved biologic treatments for inflammatory bowel diseases[16,117,118]

Medication	Route of administration (IV, SC, PO)	Approved dose
Infliximab	IV	Induction: 5-10 mg/kg (weeks 0, 2, and 6) Maintenance: 5-10 mg/kg every 4-8 wk
Adalimumab	SC	Induction: 160 mg (week 0), 80 mg (week 2) Maintenance: 40 mg every 7-14 d
Golimumab	SC	Induction: 200 mg (week 0), 100 mg (week 2) Maintenance: 100 mg every 4 wk
Certolizumab	SC	Induction: 400 mg (weeks 0, 2, and 4) Maintenance: 400 mg every 4 wk
Vedolizumab	IV	Induction: 300 mg (weeks 0, 2, and 6) Maintenance: 300 mg every 4-8 wk
Ustekinumab	IV SC	Induction: < 55 kg: 260 mg 55-85 kg: 390 mg > 85 kg: 520 mg Maintenance: 90 mg every 8 wk

Table 2 Biologic agents which have demonstrated efficacy in inflammatory bowel diseases and rheumatology

	Mechanism of action	UC	CD	2Fistulization	Ankylosing Spondylitis	Psoriasis
Anti-TNF
1Infliximab[20,22,51,119]	Chimeric monoclonal antibody	x	x	x	x	x
Adalimumab[26,28,54,120,121]	Fully human monoclonal antibody	x	x	x	x	x
Certolizumab[31,122,123]	Pegylated humanized monoclonal antibody Fab' fragment		x	+/-	x	x
Golimumab[57,122,124]	Fully human monoclonal antibody	x			x	x
Anti-integrin
4Natalizumab[39]	Chimeric monoclonal antibody against α4 integrin		x
3Vedolizumab[46,96]	Chimeric monoclonal antibody against α4β7 integrin	x	x	+/-
Ustekinumab[50,125,126]	Fully human monoclonal antibody against P40 sub-unit of IL-12 and IL-23		x	+/-	x	x

¹Infliximab is the only biologic which has been evaluated to be an effective ‘rescue’ agent. Evidence is lacking for the remaining biologics;

²Improvement in fistulizing disease was evaluated as a primary outcome only in infliximab. Efficacy was otherwise determined indirectly from secondary outcomes, subgroup analyses and small scale studies for the remaining biologics;

³Consider the use of vedolizumab as a first-line biologic agent in patients at high risk for infectious complications. Vedolizumab has a slower onset of action (approximately 6-8 wk) as compared to alternate biologics;

⁴Use of natalizumab is contraindicated if the patient is JC virus antibody positive due to the risk of progressive multifocal leukoencephalopathy. UD: Ulcerative colitis; CD: Crohn’s disease.

Table 3 Recommendations for treating to target in Crohn’s disease by the International Organization for the Study of Inflammatory Bowel Diseases[19]

Crohn’s disease	Ulcerative colitis
The consensus target is a combination of:
Clinical/1PRO remission defined as resolution of abdominal pain and diarrhea or altered bowel habits which should be assessed every 3 mo until resolution then 6-12 mo thereafter. and Endoscopic remission2 defined as resolution of ulceration at ileocolonoscopy which should be assessed at 6-9 mo intervals during the active phase	Clinical/1PRO remission defined as resolution of rectal bleeding and diarrhea or altered bowel habits which should be assessed every 3 mo until resolution then 6-12 mo thereafter. and Endoscopic remission2 defined as resolution of friability and ulceration at flexible sigmoidoscopy or colonoscopy3 which should be assessed at 3 mo intervals during the active phase
Adjunctive measures of disease activity that may be useful in the management of selected patients but are not a treatment target include:
•Faecal calprotectin	•CRP •Faecal calprotectin •Histology
Measures of disease activity that are not a target:
•Histology •Cross-sectional imaging	•Cross-sectional imaging

¹Patient reported outcomes;

²When endoscopy cannot adequately evaluate inflammation, resolution of inflammation as assessed by cross-sectional imaging can be substituted;

³While Mayo subscore of 0 may be defined as the target, there is currently insufficient evidence to recommend it in all patients; only Mayo subscore of 0-1 can be systematically recommended in practice.