Table 1.
Studies on ACT in Patients With IBD
| Authors (year) | Study design | Population | Combination (# of patients) | Safety | Efficacy |
|---|---|---|---|---|---|
| Clark-Snustad et al71 (2020) | Retrospective cohort study | 18 CD patients | Tofacitinib + ustekinumab (10) Tofacitinib + vedolizumab (7) Tofacitinib + certolizumab pegol (1) | No AEs reported | Clinical, endoscopic, and biochemical improvement |
| Dolinger et al69 (2021) | Retrospective cohort study | 16 pediatric IBD patients (9 UC/IBDunspecified, 7 CD) |
Tofacitinib + vedolizumab (9) Vedolizumab + ustekinumab (4) Tofacitinib + ustekinumab (3) | Serious AEs reported in only 1 patient (septic arthritis, deep vein thrombosis) | Corticosteroid-free remission at 6 months |
| Eronen et al68 (2022) | Retrospective cohort study | 16 IBD patients (1 UC, 15 CD) |
Vedolizumab + anti-TNF agent (6) Vedolizumab + ustekinumab (5) Ustekinumab + anti-TNF agent (5) | No serious AEs reported 3 infection complications | Clinical benefit in half of patients |
| Glassner et al62 (2020) | Retrospective cohort study | 50 IBD patients (18 UC, 31 CD, 1 IBD-undetermined) 10 with concomitant IMID Median number of failed biologic agents=2 |
53 ACT regimens: Vedolizumab + ustekinumab (25) Tofacitinib + anti-TNF agent (9) Tofacitinib + vedolizumab (8) Vedolizumab + anti-TNF agent (7) Tofacitinib + ustekinumab (3) Anti-TNF agent + apremilast (1) |
Serious AEs in 12% | Clinical remission (50% vs 14%; P=.0018; Δ36%; 95% CI, 0.13–0.53) and endoscopic remission (34% vs 6%; P=.0039; Δ28%; 95% CI, 0.09–0.47) at follow-up compared with baseline |
| Goessens et al67 (2021) | Retrospective multicenter cohort study | 98 IBD patients (40 UC, 58 CD) 41 with concomitant IMID Median number of failed biologic agents=3 |
104 ACT regimens: Vedolizumab + anti-TNF agent (41) Anti–IL-4/13, -5, -6, -12/23, -17A, or -23 agent + vedolizumab (21) Tofacitinib + vedolizumab (13) Anti-TNF agent + anti–IL-4/13, -5, -6, -12/23, -17A, or -23 agent (11) Tofacitinib + anti-TNF agent (1) Others (17) |
AEs in 42%, mostly related to uncontrolled IBD (10 significant infections, 1 skin cancer) |
Improvement of IBD disease activity in 70% Improvement of IMID/ EIM activity in 81% |
| Goyal et al70 (2020) | Retrospective cohort study | 9 pediatric refractory CD patients (1 with concomitant sacroiliitis) | Vedolizumab + anti-TNF agent (8) Infliximab + anakinra (1) | 1 serious AE (staphylococcal skin infection) | Clinical remission (44.4%) |
| Guillo et al66 (2023) | Ambispective cohort study | 213 IMIDs (91 CD, 54 axial spondyloarthritis, 20 UC, 13 rheumatoid arthritis, 9 psoriatic arthritis, 8 psoriasis, 18 others) 73 with 1 IMID 70 with ≥2 IMIDs |
Vedolizumab + anti-TNF agent (73) Ustekinumab + anti-TNF agent (70) Vedolizumab + ustekinumab (12) |
27 infections reported 3 serious infections leading to discontinuation (Clostridioides difficile colitis, Pseudomonas aeruginosa lung infection, hemophagocytic syndrome related to zoonosis) |
Significant improvement in patient-reported outcomes (50%) Mild-to-moderate improvement (27%) |
| Kwapisz et al63 (2021) | Retrospective cohort study | 15 refractory IBD Patients (1 UC, 14 CD) Median number of failed biologic agents=3.8 |
Vedolizumab + anti-TNF agent (8) Vedolizumab + ustekinumab (5) Ustekinumab + anti-TNF agent (2) |
Infections requiring antibiotics in 27% 3 hospitalizations 3 surgeries 1 discontinuation |
Symptomatic improvement in 73% Reduction of corticosteroid use in 67% Endoscopic or radiographic improvement in 44% |
| Llano et al72 (2021) | Retrospective cohort study | 14 IBD patients (10 UC, 3 CD, 1 indeterminate colitis) |
Tofacitinib + vedolizumab (9) Vedolizumab + ustekinumab (3) Vedolizumab + anti-TNF agent (2) |
No serious AEs (4 infections reported) | Clinical improvement and biochemical response (>50%) |
| Lee et al73 (2022) | Retrospective cohort study | 19 refractory CD patients 18 with prior failure of ≥2 biologic agents |
Tofacitinib + ustekinumab (11) Tofacitinib + vedolizumab (7) Tofacitinib + certolizumab pegol (1) |
AEs in 36.8% of patients (minor infections or CD flares) No serious AEs |
Clinical response (80%) Clinical remission (60%) Endoscopic improvement (54.5%) |
| Privitera et al64 (2020) | Retrospective cohort study | 16 IBD patients (5 UC, 11 CD) 7 with uncontrolled IBD 9 with concomitant IMID |
Vedolizumab + anti-TNF agent (6) Ustekinumab + anti-TNF agent (4) Vedolizumab + ustekinumab (3) Vedolizumab + secukinumab (2) Vedolizumab + apremilast (1) |
AEs in 18.8% 1 discontinuation |
Clinical response in 100% |
| Yang et al65 (2020) | Retrospective cohort study | 22 refractory CD patients Median number of failed biologic agents=4 |
24 ACT regimens: Vedolizumab + anti-TNF agent (13) Vedolizumab + ustekinumab (8) Ustekinumab + adalimumab (2) Ustekinumab + infliximab (1) |
AEs in 13% | Endoscopic improvement in 43% Endoscopic remission in 26% Clinical response in 50% Clinical remission in 41% Significant posttreatment reduction in median SES-CD (from 14 to 6; P<.05) and PRO-2 (from 24.1 to 13.4; P<.05) |
ACT, advanced combination treatment; AE, adverse event; CD, Crohn’s disease; EIM, extraintestinal manifestation; IBD, inflammatory bowel disease; IL, interleukin; IMID, immune-mediated inflammatory disease; PRO-2, patient-reported outcome-2 score; SES-CD, Simplified Endoscopic Score–Crohn’s Disease; TNF, tumor necrosis factor; UC, ulcerative colitis.