UEG Week Virtual 2021 Congress Review - 14

UEG Week Congress Review
Scientific Programme Highlights
Filgotinib most effective in biologicnaïve
and early-line treatment of UC
patients
A post-hoc analysis of the Phase 2/3 SELECTION
study1 has confirmed that oral filgotinib 200 mg/
day is effective for induction and maintenance
treatment of both biologic-naïve and -experienced
patients with moderately to severely active UC,
but that the treatment works best in biologicnaïve
patients or when used after failure of only
one biologic or mechanism of action (MOA)
(tumour necrosis factor antagonist or integrin
inhibitor [vedolizumab]).
SELECTION was a randomised, double-blind, placebo-controlled
study including two induction studies (one in biologic-naïve and
one in biologic-experienced patients), and one maintenance
study.1
Eligible patients were aged 18-75 years with moderately
to severely active UC (total Mayo Clinic Score [MCS]: 6-12) for ≥6
months before enrolment. Patients were randomised to receive
oral filgotinib 100 mg, 200 mg, or placebo, once daily for 11 weeks.
Patients in clinical remission or with an MCS response at Week
10 were re-randomised to continue their induction regimen or to
placebo from Weeks 11 to 58. The primary endpoint of the study
was clinical remission at Weeks 10 and 58.
At Week 10, filgotinib 200 mg/day (but not 100 mg/day) was
significantly more effective than placebo in achieving clinical
remission in both biologic-naïve (26.1% vs. 15.3%; p=0.0157) and
biologic-experienced (11.5% vs. 4.2%; p=0.0103) patients.
In the most recent analysis, which was presented at UEG Week
Virtual 2021 by Iris Dotan from the Rabin Medical Centre in Petah
Tikva, Israel, among biologic-experienced patients, filgotinib 200
mg/day was significantly more effective than placebo at inducing
clinical remission at Week 10 only in patients with one prior
biologic failure or failure of one MOA: one biologic failure: 16.3%
vs. 2.0% (p=0.0069), one MOA failure: 15.1% vs. 4.4% (p=0.0314),
two or more biologic failures: 7.4% vs. 3.7% (p=0.3886), two MOA
failures: 6.7% vs. 1.6% (p=0.1653). At Week 58, significantly higher
proportions of biologic-naïve and -experienced responders with
failure of two or more biologics or two MOAs treated with filgotinib
200 mg achieved clinical remission compared with those treated
with placebo (all p<0.05).
The investigators concluded that, based on the results of the
induction studies, filgotinib 200 mg/day is most effective in
biologic-naïve patients and those who switch after failure of
only one biologic or MOA.
Low-intensity HSCT produces
promising efficacy in CD but fails on
safety grounds
A multicentre, randomised controlled study
investigating low-intensity autologous stem cell
transplantation (HSCT) in treatment-refractory
CD has reported meaningful reductions in
endoscopic disease activity, but the study was
halted early due to safety concerns. The UKbased
ASTIClite study, which was described by
James Lindsay from Barts and London School of
Medicine in the UK, had a target enrolment of 99
CD patients, with 23 patients randomised prior to
study cessation.
As James Lindsay explained, initial reports of benefit from HSCT
were tempered by the results of the ASTIC trial, which failed to
meet its ambitious primary endpoint of clinical, endoscopic
and radiological remission off all treatment, and reported
significant side effects considered secondary to high doses of
cyclophosphamide.1
Subsequent analyses found complete
regression of ulceration in 50% of ASTIC study participants,2
encouraging investigators to initiate the ASTIClite study of low
intensity HSCT compared with standard of care (SOC) using
mucosal healing as the primary endpoint.
The ASTIClite study enrolled adults with active CD ulceration
(Simple Endoscopic Score for Crohn's Disease [SES-CD]) ulcer score
≥2) who were refractory to at least two classes of biologic agents
and who were not candidates for surgery. The primary endpoint of
the study was centrally read endoscopic remission (SES-CD ulcer
subscore of 0) without requirement for surgery or death at Week 48.
Of the 23 patients randomised, 13 received HSCT with a low
intensity regimen and 10 received SOC. The centrally-read
primary outcome was achieved 3/7 patients (43%) who received
HSCT compared with 0/9 patients (0%) who received SOC.
Locally-read SES-CD scores were available for a further three
patients (two HSCT patients who achieved complete ulcer
healing and one SOC patient who did not).
Serious adverse events occurred in all 13 HSCT patients and
4/10 (40%) SOC patients. Ten serious unexpected severe adverse
reactions were reported in six HSCT patients, including three
cases of delayed renal failure due to thrombotic microangiopathy.
Two patients in the HSCT arm died (one from pulmonary venous
occlusive disease at Week 24 and one from respiratory failure at
Week 60).
According to the investigators, although HSCT using a reduced
intensity regimen led to regression of all endoscopic ulceration in
some patients, the significant adverse event profile observed in this
study preclude its future use in clinical practice. Work is ongoing
to try and determine the mechanisms underlying these findings.
1. Feagan BG, et al. Lancet 2021;397(10292):2372-2384.
14
1. Hawkley CJ, et al. JAMA 2015;314(23):2524-2534.
2. Lindsay JO, et al. Lancet Gastroenterol Hepatol 2017;2(6):399-406.

https://www.ueg.eu/library/efficacy-of-filgotinib-in-patients-with-ulcerative-colitis-by-line-of-therapy-in-the-phase-2b-3-selection-trialefficacy-of-filgotinib-in-patients-with-ulcerative-colitis-by-line-of-therapy-in-the-phase-2b-3-selection-trial/248436 https://www.ueg.eu/library/a-randomised-controlled-clinical-trial-of-autologous-stem-cell-transplantation-hsct-in-patients-with-treatment-refractory-crohn-s-disease-low-intensity-therapy-evaluation-asticlite/248437

UEG Week Virtual 2021 Congress Review

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