Small bowel capsule endoscopy and treat-to-target in Crohn's disease: A systematic review

Table 2 Studies evaluating the use of small bowel capsule endoscopy in the assessment of mucosal healing in patients diagnosed with Crohn’s disease

Ref.	Study design	Sample size	Treatment evaluated	Prior biologic exposure	Interval between the CE	CE findings considered for assessing mucosal healing	Positive SB findings before treatment	Positive SB findings after treatment	P-value
Efthymiou et al[85], 2008	Prospective, blinded	40	CS (60%) Mesalamine (70%) Azathioprine (10%) Infliximab (5%) Metronidazo-le (20%)	-	After achievement of clinical remission: 4 wk (75%)	Number of apthous ulcers, mean ± SE	26.0 ± 7.5	12.7 ± 2.3	0.07
					6 wk (15%)	Number of large ulcers, mean ± SE	8.3 ± 1.4	5.0 ± 0.8	0.01
					8 wk (10%)	Percentage of the SBTT in which any endoscopic lesion was visible, mean ± SE	22.0 ± 3.1	17.8 ± 2.5	0.08
Tsibouris et al[86], 2013	Prospective, blinded	1021	-	-	≥ 15 d after CDAI dropped < 150: 2-3 mo; (26.5%) 3-6 mo; (19.6%) 6-12 mo; (53.9%)	CECDAI score, mean ± SD	14 ± 6	4 ± 2	-
Niv et al[44], 2014	Prospective, blinded	19	Copaxone (68.4%) 5-ASA (52.6%) Antibiotics (15.8%) CS (5.3%) IS (10.5%) Vitamins (26.3%) Others (36.8%)	-	12 wk	Lewis score, mean ± SD	1730 ± 1780	No correlation between changes in CDAI/IBDQ and Lewis score2	-
Hall et al[42], 2014	Prospective, blinded	43	Adalimumab (84%) 160 mg W0, 80 mg W2, then 40 mg /2 wk or Azathioprine (16%) 2-2.5 mg/kg	Naïve 38/43 Exposed 5/43	52 wk3	Complete MH = Absence of ulcers, n (%) Normalizatio-n of CECDAI score < 3.5, n (%) Change in CECDAI score, n (%)	- - CECDAI < 3.5: 4/43 (9%) 3.5 ≤ CECDAI < 5.8: 13/43 (30%) CECDAI ≥ 5.8: 26/43 (61%)	Complete MH: 12/28 (43%) CECDAI < 3.5: 2/28 (7%) CECDAI ≤ 3.5 < 5.8: 6/28 (21%) CECDAI ≥ 5.8: 8/28 (29%)	< 0.0001
Kopylov et al[45], 2015	Prospective	52	None (15.4%) 5-ASA (9.6%) Thiopurine (36.6%) Anti-TNF (26.9%) Anti-TNF+IS (11.5%)	-	NA Included patients were all in clinical remission (CDAI < 150) and had only one CE.	MH = Lewis score < 135	NA	MH: 8/52 (15.4%) 135 ≤ Lewis < 790: 33/52 (63.5%) Lewis score ≥ 790: 11/52 (21.2%)	-
Shafran et al[43], 2016	Prospective, open-label	15	Certolizumab pegol 400 mg W0, W2, W4 then /4 wk	Naïve 3/15 Exposed 12/154	24 wk in responders	Lewis score, mean	1663	226	-
Aggarwal et al[46], 2017	Prospective, blinded	43	None (14%) 5-ASA (60%) CS (12%) IS (74%) Anti-TNF (21%)	-	NA Included patients were all in clinical remission (CDAI < 150) and had only one CE.	MH = Lewis score < 135	NA	MH: 17/43 (40%) 135 ≤ Lewis < 790: 19/43 (44%) Lewis score ≥ 790: 7/43 (16%) Significant correlation between Lewis score and fecal calprotectin (r = 0.82, P < 0.0001)	-
Mitselos et al[47], 2018	Retrospective	30	None (37%) 5-ASA (17%) Budesonide (10%) Azathioprine (10%) Anti-TNF (20%) Anti-TNF+IS (6%)	-	NA Included patients had only one CE (60% in both clinical and biochemical remission)	MH = Lewis score < 1355	NA	MH: 6/15 (40%) Weak correlation between CDAI and Lewis score (r = 0.32, P = 0.088) and between CRP and Lewis score (r = 0.52, P = 0.004)	-
Nakamura et al[87], 2018	Prospective, blinded	92	None (27%) 5-ASA (18%) Thiopurines (17%) Infliximab (20%); Adalimumab (10%) Elemental diet (5%) CS (3%)	Naïve 38/92Exposed 54/92	6 mo in the active group (40/92) Non-active patients ended the study at baseline (52/92)	Lewis score, mean MH = Lewis score of 0 Active CD: Lewis score > 135	458	233 MH: 2/296 Improvement of LS in all 7 patients who received biologics, and in 8/11 (73%) of asymptomatic patients receiving additional medication	0.0004

¹Eighteen percent of patients had Crohn’s disease restricted to the colon;

²Nine patients did not have CE at week 12;

³Fifteen patients did not have CE at week 52;

⁴Two patients had an allergic reaction to infliximab, 10 patients were secondary non-responders to infliximab and/or adalimumab;

⁵Data presented for patients in both clinical and biochemical remission (CDAI<150 and CRP < 5 mg/L);

⁶Of 40 patients in the active group, 29 (72%) underwent follow-up CE to assess the therapeutic effect on MH. ASA: Aminosalicylic acid; CD: Crohn’s disease; CE: Capsule endoscopy; CECDAI: Capsule Endoscopy Crohn's Disease Activity Index; CS: Corticosteroids; IS: Immunosuppressant; LS: Lewis score; MH: Mucosal healing; SB: Small bowel; SBTT: Small bowel transit time.