Introduction
Guselkumab (GUS) is an interleukin-23p19 inhibitor that is approved for treatment of ulcerative colitis (UC) and Crohn's disease (CD), but timing of and ability to achieve transmural healing (TH) is unknown. Intestinal ultrasound (IUS) is a sensitive and specific modality to assess for treatment response in UC and CD. Here we report our real-world experience of assessment of sonographic healing to GUS in IBD patients (pts).
Aims & Methods
Pts with sonographic disease activity on IUS before GUS initiation were included. Pts received standard induction dosing of either 400 mg subcutaneously or 200 mg intravenously at weeks 0, 4, and 8. We employed a prospective monitoring protocol across our IBD center for pts with UC and CD initiating GUS treatment, including assessment of clinical, biochemical, and sonographic disease activity prior to, and at 12 ± 6 weeks, from GUS initiation. Clinical remission was defined as Simple Clinical Colitis Activity Index (SCCAI) <3 in UC or Harvey-Bradshaw Index (HBI) <5 in CD.1,2 Biochemical response was defined as reduction in fecal calprotectin (FCP) by 50%. The IBUS-Segmental Activity Score (IBUS-SAS) for CD and Milan Ultrasound Criteria (MUC) for UC were calculated.3,4 Sonographic response was defined as reduction of bowel wall thickness (BWT) ≥25% or >2.0 mm, or by >1.0 mm and one-color Doppler signal (CDS), in the most inflamed bowel segment. TH was defined as BWT ≤3mm and normal CDS in all bowel segments. Primary outcome was sonographic response at follow up (f/u) IUS. Secondary outcomes were clinical remission, biochemical response, and TH.
Results
33 pts (9 UC, 24 CD) were included (Table 1). 7 (77.8%) UC and 11 (45.8%) CD achieved sonographic response at f/u; 6 (66.6%) UC, 5 (20.1%) CD achieved TH. There was no difference in response rates between CD pts with colonic versus ileal disease (p= 0.697). There was a significant reduction in MUC (p=0.026) and IBUS-SAS (p=0.016) scores from GUS initiation.
Of 13 pts (5 UC, 8 CD) with clinical disease at baseline, 4 (80%) UC, 5 (62.5%) CD achieved clinical remission at f/u. Of 15 pts (5 UC, 10 CD) with elevated FCP at GUS initiation, 4 (80.0%) UC, 3 (30%) CD had biochemical response.
Both clinical and biochemical response demonstrated a strong positive association with sonographic response, φ = 0.548 (p=0.053) and φ = 0.449 (p=0.166), respectively.
Diagnosis | UC (n=9) | CD (n=24) |
Female sex – n (%)
Age – median (IQR)
Disease duration – median (IQR)
Disease phenotype – n (%)
Left-sided UC (distal colitis)
Extensive (pancolitis)
Ileal
Colonic
Ileocolonic
Prior resection – n (%)
Medication history – n (%)
IL23 inhibitor-experienced
Prior exposure to >2 advanced therapies
Concomitant medications at GUS initiation | 5 (55.6)
42 (31-56)
8 (2.5-21)
2 (22.2)
7 (77.8)
0 (0)
3 (33.3)
4 (44.4)
2 (1 upadacitinib, 1 mesalamine)
| 17 (70.8)
49.5 (31-64)
13.5 (3.5-22)
9 (37.5)
7 (29.2)
8 (33.3)
7 (29.2)
11 (45.8)
11 (45.8)
1 (infliximab)
|
| | Baseline | Follow up | P-value | Baseline | Follow up | P-value |
| Time from GUS initiation to follow up IUS (days) – median (IQR) |
| 90 (63-103) |
|
| 88 (71-108.5) |
|
| Maximal colonic/TI BWT (mm) – median (IQR) | 4
(3.6-4.95) | 3
(1.55-4) | 0.008 | 4.35
(3.45-5.05) | 3.8
(2.6-4.35) | 0.007 |
| MUC/IBUS-SAS – median (IQR) | 7.56
(5.25-8.11) | 4.2
(2.17-7.44) | 0.026 | 24.4
(20.1-39.3) | 19.5
(12.3-26.7) | 0.016 |
| HBI/SCCAI – median (IQR) | 4 (0.5-5) | 0 (0-2) | 0.069 | 2 (1-5.5) | 1 (0-5) | 0.21 |
| FCP (µg/g) – median (IQR) | 1469
(808.5-1894.5) | 158
(50-196) | 0.008 | 202
(99.9-1820) | 236
(30-807) | 0.523 |
| Corticosteroid use – n (%) | 2 (22.2) | 2 (22.2) | 1.000 | 5 (20.8) | 1 (4.2) | 0.188 |
Conclusion
In this real-world study, GUS was effective in achieving TH by 12 weeks in patients with UC or CD. These findings provide new insight into the timing of this important evolving endpoint in pts with IBD.
References
- Harvey, Bradshaw. A simple index of Crohn’s-disease activity. The Lancet. 1980;(8167):514.
- Walmsley RS, Ayres RCS, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998;43(1):29-32. doi:10.1136/gut.43.1.29
- Novak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn’s Disease. J Crohns Colitis. 2021;15(4):609-616. doi:10.1093/ecco-jcc/jjaa216
- Allocca M, Filippi E, Costantino A, et al. Milan ultrasound criteria are accurate in assessing disease activity in ulcerative colitis: external validation. United Eur Gastroenterol J. 2021;9(4):438-442. doi: 10.1177/2050640620980203
Disclosure
C.M.D, K.S.B, T.G. and A.K. have nothing to disclose.
D.C. has served on the speaker bureau for Janssen Pharmaceuticals, Abbvie, Eli Lilly; and has served as a consultant to Bristol Myers Squibb, and Boehringer Ingelheim, Abbvie, Eli Lilly, Janssen Pharmaceuticals, Pfizer.
N.K.C. has served as a consultant for NeuroLogica (a subsidiary of Samsung Electronics), Johnson & Johnson Pharmaceuticals, GE Healthcare, Abbvie, and Sanofi
D.T.R. reports speaker or consultant fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, BMS, CDx Diagnostics, Syneos, Check-Cap, Dizal Pharmaceuticals, Genentech (Roche), Gilead Sciences, Ichnos Sciences (formerly Glenmark Pharmaceuticals), InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Narrow River Management, Pfizer, Prometheus Laboratories, Reistone, Takeda, and Techlab; and research grants from Takeda.
