Author, year
| UGI Subset population
| Study design, duration of follow-up | Interventions Studied
| Outcomes measured | Key Numeric Results
| Authors’ Main Interpretations
|
D'Haens et.al [DIVERGENCE 1]. (2023)
D'Haens et.al. (1994)
Miehsler et.al. (2001)
| 17 adults, jejununal
14 adults, esophageal
32 adults, UGI
| RCT, 24 weeks
Retrospective observational, 12 years
Retrospective observational, 34 mos. | Filgotinib, Placebo
“Usual therapy”: Steroids ± 5-ASA +/- Abx, immunomodulator ± acid suppression, no uniform prospective regimen
4 arms: PPI, 5-ASA, steroid, AZA
| MARiAseg remission at 24 weeks
Endoscopic healing, flares/relapse at follow-up
CDAI, UGI symptoms score, CRP | Non-significant. (MARiAseg mean): 0/3 PBO (6.6); 0/8 FIL 100mg (6.3); 2/6 FIL 200mg (6.8)
Significant. 69% (9/13) 64.3% (9/14) with partial or complete healing after short course steroids; 21% (3/14) had persistent disease or repeated flares.
Significant. Antisecretory drugs: UGI Symptoms score 2.5 (1-5) to 1 (0-3) P=0.039
Prednisolone: CDAI from 272 (151-451) to 100 (22-309) P= 0.03
AZA: CDAI 94 (39–426) to 57 (0–203) P=0.04; CRP 2.3 mg/dl (0.5–8.2) to 0.7 mg/dl (0.5–2.2) P=0.02
| Filgontinib did not result in statistically significant differences vs. PBO to achieve MARiAseg remission in jejunum in 24 weeks.
Esophageal CD responds to steroids in ~70%.
UGI Symptoms responded to antisecretory drugs.
CDAI decreased with Prednisolone, AZA.
CRP decreased with AZA.
|
Juillerat et.al. (2013)
Olbjorn et.al. (2014)
De Felice et.al. (2015)
| 7 adults, UGI
16 pediatric, UGI
24 adults, esophageal
| Retrospective observational, 2 years
Prospective cohort, 2 years
Retrospective observational, 1 year | Natralizumab
IFX
Alone or combination: 5-ASA, prednisone, AZA, oral budesonide , IFX, CZP, PPI
| Clinical response (HBI), completion of 1 year of treatment
Endoscopic, clinical remission maintained at 1-2 years
Clinical and endoscopic response at 1 year | Nonsignificant. 1/7 responded; 2/7 did not respond
Significant. IFX treated: from 11 with UGI CD-specific lesions at diagnosis to 2 at ff-up (61% to 12%); non IFX treated: 5/18 at dx to 2/15 at ff-up (31% to 15%)
Significant. No numeric value - patients were treated with various combinations, in this case series
| Only 1/7 responded to natralizumab; (no further comment or elaboration/subgroup analysis for UGI made for this study)
IFX resulted in a significant decrease in UGI CD-specific lesions at ff-up 1-2 years after dx. Response was sustained at 2 years for all responders.
Inflammatory esophageal CD responded to prednisone, topical budesonide, or biologics.
Stricturing esophageal CD was successfully treated with combination of biologic therapy, immunomodulators, and serial dilations with/without steroid injections.
Aggressive medical therapy with biologics for fistulizing esophageal CD, was not universally effective.
|
Lambin et al. (2020)
Wauters, et.al. (2017)
Huang et.al. (2025)
| 60 adults, UGI strictures
69 pediatric, UGI
39 adults, jejunum
| Retrospective observational, 5 years
Prospective observational cohort, 5 years
Retrospective observational cohort, 1 year | Immunomodulator (AZA, MTX), anti-TNF, anti-TNF + immunomodulator, none, UST
No control groups: corticosteroids (pred, budesonide), EEN, immunomodulators (AZA, 6-MP, MTX), anti-TNF (IFX, ADA)
IFX, UST, Vedolizumab
| Surgery free-survival at 1 and 5 years
Clinical response and remission
Endoscopic healing at 1 year | Significant. Anti-TNF alone: multivariate OR 0.2, univariate OR 0.4; 70% efficacy at 6.5mos;
anti-TNF + immunomodulators: multivariate OR 0.2 univariate OR 0.2;
61% efficacy at 23.5mos;
UST + immunomodulator: 67% efficacy at 10.5mos
UST alone: 50% efficacy, Immunomodulator alone: 50% improvement in 35mos.
Nonsignificant. No difference in time to or duration of sustained remission for anti-TNF exposed and non-anti-TNF P=0.60
Significant. After 1 year:
Jejunal endoscopic healing (EH): IFX 8/15 (53.3%), UST 3/15 (23.1%), Vedo 1/11 (9.1%);
Endoscopic response (ER): IFX 8/15 (53.3%), UST 7/13 (53.8%), Vedo 2/11 (18.2%);
Ulcer healing: IFX 8/15 (53.3%), UST 5/13 (38.5%), Vedo 1/11 (9.1%)
| Anti-TNF therapy alone or in association with an immunosuppressant reduces risk of surgery in UGI CD strictures.
No significant difference in time to or duration of sustained remission for anti-TNF exposed and non-anti-TNF P=0.60
IFX had strongest response compared to either UST or Vedolizumab for endoscopic healing, endoscopic response and ulcer healing in jejunum.
Primary outcome at 1 year for all 3 biologics in jejunum: 30.8% Endoscopic healing (EH), 43.6% achieved endoscopic response (ER), 35.9% had ulcer healing (UH)
|
Vale Rodrigues et.al. (2020)
Yamamoto et.al. (2009)
Tang et.al. (2024)
Lui et.al. (2017)
Annunziata et.al. (2012)
Anton et.al. (2001)
| 40 adults, esophageal
54 adults, gastroduodenal CD
54 pediatric, UGI
39 adults, esophageal
19 adults, UGI
20 adults, esophageal | Retrospective observational
Retrospective observational, 12 years
Retrospective observational, 6 weeks and at 1 year
Retrospective observational, 4 years
Prospective cohort, 12 weeks
Retrospective observational, 1mo - 28 years | PPI, corticosteroids, 5-ASA, anti-TNF, thioprurines, EEN
Medical therapy in 31/54: corticosteroids, 5-ASA, AZA, PPI alone or combination
EEN
anti-TNF, anti-integrin, anti-IL12/23, combination
Group A: PPI + anti-TNF (IFX, ADA) + 5-asa, AZA, 6MP;
Group B: PPI + 5-ASA, AZA, 6MP
5-ASA, H2RA, PPI, Steroids, immunomodulator | Clinical and endoscopic remission
Clinical response
Endoscopic healing
Clinical response/remission, endoscopic response/remission
Endoscopic healing at 12 weeks
Clinical, endoscopic improvement | Significant. 37/40 (92.5%) tx w/ PPI; 33/40 (82.5%) treated w/ >1 drug; 33/40 (82.5%) with 1st line therapy had complete resolution in 7mos.
Nonsignificant. 14/31 (45%) responded to medical tx; 19/31 required surgery, 12 did not require surgery
Significant. Upper GI location (OR 0.25, 95% CI 0.11–0.55, P = 0.001) associated with segmental mucosal healing (MH) at EEN completion.
EEN had 35% MH for small bowel.
Significant. anti-TNF resulted in greater clinical (P=0.02) & endoscopic (p<0.01) response and clinical remission (P=0.01) but not endoscopic remission (P=0.85); anti-integrin poorer endoscopic response when tx w/ other biologics (P<0.03) & not assoc. with significant clinical response; anti-IL12/23 compared w/ other biologics assoc. w/ poorer clinical (P<0.01) and endoscopic response (P=0.03); no sig diff bet'n anti-integrin and IL12/23 clin response (P=0.13), clin remission (P=0.34), endoscopic response (P>0.99) and endoscopic remission (P>0.99).
Significant. 100% of symptomatic patients improved. Group A: Mucosal healing in 8/11 (72.7%), endoscopic healing in 7/8; Group B: 1/8 (12.5%) mucosal healing (P=0.001)
Significant. Steroids 9/18 improvement, AZA 2/8, 6-MP 2/3, PPI 2/5 | Clinical and endoscopic remission was achieved in more than 80% of the patients, majority with PPI.
Medical therapy not effective for UGI CD, although corticosteroids most widely used.
UGI segment in pediatric CD was associated with segmental mucosal healing following EEN therapy. Lewis score significantly improved following EEN treatment, the MH rate was only 35%, and lesions in the small bowel were more likely to worsen after EEN therapy despite anti-TNF maintenance therapy
The timing of biologic initiation in patients in this study was not significantly associated with improved clinical or endoscopic outcomes.
Treatment with anti-TNF therapy, when given as first-line treatment associated with better clinical and endoscopic outcomes when compared to other second- or third-line biologic therapies.
Mucosal healing achieved in 70% of PPI plus anti-TNF and only in 12.5% of PPI plus other treatments group
First line therapy with steroids, 5-ASA, H2RA, PPI resulted to improvement in 50% of patients
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