Articles

Appendicectomy plus standard medical therapy versus

standard medical therapy alone for maintenance of
remission in ulcerative colitis (ACCURE): a pragmatic,
open-label, international, randomised trial
The ACCURE Study Group*

Summary
Lancet Gastroenterol Hepatol Background The appendix might have an immunomodulatory role in ulcerative colitis. Appendicectomy has been
2025; 10: 550–61 suggested as a potentially therapeutic intervention to maintain remission in ulcerative colitis. We aimed to evaluate
Published Online the clinical effectiveness of laparoscopic appendicectomy in maintaining remission in patients with ulcerative colitis.
April 11, 2025
https://doi.org/10.1016/
S2468-1253(25)00026-3 Methods We did a pragmatic, open-label, international, randomised controlled superiority trial in 22 centres across
See Comment page 497
the Netherlands, Ireland, and the UK. Patients with established ulcerative colitis who were in remission but had been
*Members listed at the end of
treated for disease relapse within the preceding 12 months were randomly assigned (1:1) to undergo appendicectomy
the Article and in the appendix plus continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone
(pp 2–3) (control group). Randomisation was done with a central, computer-generated allocation concealment, stratified by
Correspondence to: disease extent. Patients and treating physicians were unmasked to group allocation. The prespecified primary outcome
Dr Christianne J Buskens, was the proportion of patients with a disease relapse within 1 year, predefined as a total Mayo score of 5 or higher with
Department of Surgery,
an endoscopic subscore of 2 or 3, or, in absence of endoscopy, based on a centrally independent masked review by a
Amsterdam UMC, University
of Amsterdam, critical event committee as an exacerbation of abdominal symptoms (eg, elevated stool frequency subscore of ≥1 point
1081 HV Amsterdam, from baseline) with a rectal bleeding subscore of ≥1 or faecal calprotectin level above 150 µg/g or necessitating
Netherlands treatment intensification other than mesalazine. Analyses were done on an intention-to-treat principle. This trial is
[email protected]
complete and was registered with the Netherlands Trial Register (NTR2883) and ISRCTN (ISRCTN60945764).
See Online for appendix

Findings Between Sept 20, 2012, and Sept 21, 2022, 1386 patients were screened. 201 patients were randomly assigned
to the appendicectomy group (n=101) or the control group (n=100). After exclusion of four patients due to eligibility
violations (three had active disease and one received biological agents at time of randomisation), 99 patients in the
appendicectomy group and 98 patients in the control group were included in the intention-to-treat analyses. The
1-year relapse rate was significantly lower in the appendicectomy group than in the control group (36 [36%] of 99 patients
vs 55 [56%] of 98 patients; relative risk 0·65 [95% CI 0·47–0·89]; p=0·005; adjusted p=0·002). Adverse events occurred
in 11 (11%) of 96 patients in the appendicectomy group and 10 (10%) of 101 patients in the control group. The most
frequently reported adverse events were postoperative temporary self-limiting abdominal pain in the appendicectomy
group (three [3%] patients) and skin rash in the control group (three [3%] patients). Two cases (2%) of low-grade
appendiceal mucinous neoplasm were incidentally found in resected appendix specimens in the appendicectomy
group. Serious adverse events occurred in two (2%) of 96 patients who underwent appendicectomy and none in the
control group. There were no deaths.

Interpretation Appendicectomy is superior to standard medical therapy alone in maintaining remission in patients
with ulcerative colitis.

Funding Fonds Nuts-Ohra and National Institute for Health Research Efficacy and Mechanism Evaluation.

Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND
4.0 license.

Introduction involving the entire colon (pancolitis). Clinical symptoms

Ulcerative colitis is a chronic inflammatory bowel disease of active colitis include frequent and urgent bowel
affecting an estimated 5 million individuals globally movements, rectal bleeding, abdominal pain, and
as of 2023, with a rising incidence worldwide.1–3 This fatigue, and the condition is associated with an impaired
disease affects the mucosal layer of the colon and rectum, health-related quality of life.4–6
and is characterised by a relapsing-remitting course. The The therapeutic goal in ulcerative colitis is to maintain
inflammation typically starts in the rectum (proctitis) health and related quality of life and avoid disability by
and with subsequent relapses it might extend proximally, adequately inducing and maintaining clinical and

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Research in context
Evidence before this study ulcerosa”[Title/Abstract] OR “ulcerative proctocolitis”[Title/
An inverse association between appendicectomy and the Abstract]) AND (“Randomized Controlled Trial”[Publication
development of ulcerative colitis was first reported in 1987, Type] OR “Controlled Clinical Trial”[Publication Type] OR
with subsequent case-control studies confirming this “random*”[Title/Abstract] OR “crossover*”[Title/Abstract] OR
observation, and suggesting a possible role of the appendix in “cross over*”[Title/Abstract] OR (“doubl*”[Title/Abstract] AND
ulcerative colitis. In 2016, our research group did a systematic “blind*”[Title/Abstract]) OR (“singl*”[Title/Abstract] AND
review and meta-analysis of available (case-control) studies. “blind*”[Title/Abstract]) OR “trial*”[Title/Abstract] OR
This analysis showed that previous appendicectomy was “intervention stud*”[Title/Abstract]). This searched confirmed
associated with a significantly reduced risk of developing that no randomised controlled trial of appendicectomy as an
ulcerative colitis, with an overall odds ratio of 0·39 (95% CI intervention in ulcerative colitis has been done to date.
0·29–0·52). Additionally, in 2012, our group published a
Added value of this study
systematic review assessing the effect of appendicectomy on
The ACCURE trial is the first randomised controlled trial
the clinical course of ulcerative colitis. This review included
evaluating the clinical effectiveness of appendicectomy in
six observational studies (five case-control studies and
maintaining remission in patients with ulcerative colitis
one cohort study) comprising 2532 patients. Although the
without advanced medical therapy (ie, biologicals or small
heterogeneity among these studies precluded a formal meta-
molecules). This trial shows that laparoscopic appendicectomy,
analysis, and data were scarce and conflicting, most studies
in addition to standard medical therapy, significantly reduces
suggested a beneficial effect of appendicectomy on the disease
the relapse rates within 1 year.
course in ulcerative colitis. We searched PubMed for literature
published between Jan 1, 1998, and Oct 31, 2024, using the Implications of all the available evidence
terms (“appendectomy”[MeSH Terms] OR “append*”[Title/ Appendicectomy might be an effective and safe option for
Abstract]) AND (“colitis, ulcerative”[MeSH Terms] OR reducing the relapse rate within 1 year in patients with
“ulcerative colitis”[Title/Abstract] OR “ulcerous colitis”[Title/ ulcerative colitis in addition to standard medical therapy,
Abstract] OR “colitis ulcerativa”[Title/Abstract] OR “colitis offering a potential addition to standard medical therapies.

endo­scopic remission.7 Therefore, current medical the UK. The central ethics committee and institutional
therapy follows a step-up strategy to reduce inflam­ review board at each participating Dutch and Irish site,
mation until remission is reached, thereby preventing and the Research Ethical Committee in the UK approved
disease-related complications, such as colectomy, and the trial protocol and any amendments. The final versions
development of colorectal neoplasia.8 of the protocol and statistical analysis plan were completed
The cause of ulcerative colitis is multifactorial, on May 18, 2021, and Aug 28, 2023, respectively.13,14 Patient
encompassing genetic predispositions, environmental enrolment was completed on Sept 29, 2022, with database
triggers, microbial composition, and dysregulated closure on Jan 26, 2024. The trial adhered to Good Clinical
immune responses. Recent studies9,10 have high­lighted Practice guidelines and the Declaration of Helsinki.15
the potential immunomodulatory role of the appendix in Written informed consent was obtained from all patients
ulcerative colitis. The appendix is thought to have an before trial-related procedures. This trial is registered
important role by producing inflammatory cytokines, with the Netherlands Trial Register (NTR2883) and
triggering cascade responses and thereby contributing to ISRCTN (ISRCTN60945764).
disease progression.9,10 Preliminary case-control and
small-scale cohort studies have indicated the potential Patients
beneficial effects of appendicectomy and suggested it Eligible patients were aged 18 years or older, had
as a therapeutic strategy supplementing medical treat­ established ulcerative colitis and were in remission, but
ments, which form the mainstay of modern ulcerative had required treatment for an episode of active disease
colitis management.11,12 No randomised controlled trial within the preceding 12 months. Remission was defined
of this intervention has been done to date. We aimed as a Mayo score of 2 or lower, with stool frequency,
to evaluate the clinical effectiveness of laparoscopic rectal bleeding, and physician’s global assessment
appendicectomy in maintaining remission in patients subscores of 0 or 1, confirmed by a Mayo endoscopic
with ulcerative colitis. score of 0 or 1 within 3 months before randomisation.16
In cases in which endoscopy could not be done due to
Methods restrictions during the COVID-19 pandemic, a protocol
Study design amendment in 2020 allowed remission to be confirmed
We did this investigator-initiated, two-arm, pragmatic, by a faecal calprotectin level of below 150 µg/g in patients
open-label, international, randomised controlled super­ with a previously documented history of raised faecal
iority trial at 22 sites across the Netherlands, Ireland, and calprotectin levels (>500 µg/g) during a previous disease

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flare. Patients were excluded if they had previous done at the time of clinical suspicion of a relapse or at the
appendicectomy or major abdominal surgery that would end of the 12-month trial period to objectively assess
preclude a safe procedure; suspicion of Crohn’s disease; mucosal appearance and determine the total Mayo score.
received any biological agents within 3 months before Health-related quality of life was measured with the
randomisation; a partial Mayo score of 3 or more; an EQ-5D 3-level utility score (EQ-5D-3L; range –0·33 to 1·00,
endoscopic Mayo score of more than 1; or medical with higher scores indicating better health status),18 the
comorbidities that increase perioperative morbidity. All European Organisation for Research and Treatment of
endoscopy and faecal calprotectin assess­ ments were Cancer quality of life core score (EORTC QLQ-C30;
done locally, with calprotectin used only when endo­ range 0 to 100, with higher scores indicating better global
scopy could not be done, such as during COVID-19 quality of life),19 and Inflammatory Bowel Disease
restrictions. Complete enrolment criteria are detailed in Questionnaire (IBDQ; range 32 to 224, with higher
the appendix (p 5). scores indicating better quality of life),20 and question­
naires were completed at baseline and quarterly
Randomisation and masking through­out the 12-month follow-up period. The protocol
Eligible patients were randomly assigned in a 1:1 ratio was amended after 79 patients had been enrolled to
to either undergo laparoscopic appendicectomy and remove concomitant immuno­modulators as an exclusion
continue standard medical therapy (appendicectomy criterion (to increase the trial’s generalisability and
group) or to continue standard medical treatment alone external validity, and to enhance recruitment rates) and
(control group). Randomisation was done by the research to include a dichotomous patient-reported global change
team using the computer-generated random­ isation assessment at 12 months follow-up, to assess the clinical
soft­ware ALEA and was stratified according to disease relevance of IBDQ changes. The trial design and
extent based on the Montreal classification (proctitis, left- procedures are detailed in the appendix (p 11).
sided colitis, pancolitis).17 Patients and treating physicians
were not masked to allocation during the trial. Group Outcomes
allocation was concealed from the critical event The primary outcome was the proportion of patients with
committee, which remained masked to ensure unbiased a disease relapse within 1 year. Relapse was predefined as
assessment of clinical relapses. a total Mayo score of 5 or higher with an endoscopic
subscore of 2 or 3. During the COVID-19 pandemic, the
Procedures protocol was amended to overcome logistical challenges
Patients in the appendicectomy group underwent laparo­ related to the restricted availability of endoscopic
scopic appendicectomy within 9 weeks of random­isation. procedures. To ensure the study’s continuity and maintain
The appendix, including the cuff of caecal pole data integrity, the relapse definition was expanded to
surrounding the appendiceal orifice, was removed using include, in cases of no endoscopy, an exacerbation of
a laparoscopic endostapler by or under direct supervision abdominal symptoms (elevated stool frequency subscore
of a senior colorectal surgeon; a detailed standard of ≥1 point from baseline) with a rectal bleeding subscore
operating procedure is listed in the appendix (p 6). of 1 or more, or faecal calprotectin level above 150 µg/g,
Standard day-care procedures were followed across sites, or necessitating treatment intens­ ifi­
cation other than
similar to those used for typical day-case laparoscopic mesalazine. This clinical definition was assessed in a
colorectal operations. Patients were typically discharged centrally independent review by a critical event committee,
on the same day, provided they met standard discharge comprising an inflammatory bowel disease gastro­enter­
criteria: being afebrile and clinically stable, tolerating ologist and surgeon, who were masked to group
oral intake, mobilising independently, having adequate allocation. The comprehensive relapse definition is
pain control with oral analgesia, and showing no signs available in the appendix (p 7).
of complications. No standard additional postoperative Secondary outcomes included number of relapses
antibiotics were prescribed. Both groups continued their per patient at 12 months; time to first relapse (defined as
medical therapy at the discretion of the treating the time from the date of randomisation to the first day
gastro­­enter­ologist. of clinical symptoms of an endoscopically or clinically
Follow-up included outpatient clinic visits or tele­phone confirmed relapse; patients who did not relapse during
consultations at 3, 6, 9, and 12 months after appendic­ follow-up were censored at the time of their last available
ectomy or after randomisation for the control group. follow up assessment); disease activity (as measured
Postoperative complications and surgical morbidity using the partial Mayo score at 3, 6, and 9 months, and
were assessed at 6 weeks after appendic­ectomy. Relapse the total Mayo score at 12 months); total number of
data, disease activity, outpatient clinic visits, hospital colectomies at 1 year; medication use (none, topical
admission, and medication use were assessed quarterly. therapy, oral mesalazine, systemic steroid, immuno­
Disease activity was measured using the total Mayo score modulators, and biologic agents; for each category, use
at baseline and 12 months, and the non-invasive partial was documented as a binary outcome [yes or no] at each
Mayo score at 3, 6, and 9 months.16 An endoscopy was time point) at 3, 6, 9, and 12 months; and health-related

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quality of life (EQ-5D-3L, EORTC-QLQ-C30, IBDQ at 3, A pragmatic intention-to-treat analysis was done for the
6, 9, and 12 months, and the global change assessment at primary endpoint only and included relapses during the
12 months). appendicectomy waiting period. Poisson regression was
Safety assessments were based on adverse events or done to compare the number of relapses per patient
serious adverse events that occurred between appendic­ reported with RR and 95% CIs, and Kaplan–Meier
ectomy or randomisation and the 3-month follow-up survival analysis with log-rank testing to compare the
(appendix pp 78–79). Intraoperative and postoperative time to first relapse between the groups. Medication use
complications were reported using the Clavien–Dindo over time was descriptively reported by number and
grade.21 Major complications were defined as Clavien– percentages, and generalised estimating equation was
Dindo grade of III or more. used to analyse the effect of appendicectomy on
Data on sex were reported based on medical records, medication use over time within treatment, time and the
which were documented according to the individual’s interaction between treatment, and time as model
national identification documents. No planned interim parameters, reported with odds ratios (ORs) and 95% CIs.
efficacy analysis was scheduled. However, an interim Additional generalised linear mixed models were
safety analysis was conducted by the data monitoring and applied to investigate whether a different pattern of
safety committee in March, 2021, following published change over time existed between the groups in the
research suggesting a relation between appendicectomy Mayo score and health-related quality of life, and were
and development of colorectal neoplasia in ulcerative reported with mean differences (MD) and 95% CIs.
colitis.22 The trial continued without recommendation for The optimal covariance structure for the repeated
early termination. measures data were determined based on visual

Statistical analysis
1386 patients assessed for eligibility
We assumed that the relapse rate at 12 months would be
reduced by 50%, from 40% in the control group to 20%
in the appendicectomy group. To detect this clinically 1185 excluded
relevant difference in relapse, with 80% power at a 693 ineligible
202 declined to participate
5% two-sided significant level, we calculated that 290 other reasons
82 participants per group were needed to evaluate
whether appendicectomy plus medical therapy was
201 enrolled and randomised
superior to medical therapy alone. Accounting for a
10% dropout rate, we aimed to enrol 92 patients
per group. In Sept 4, 2019, the trial started in the UK as
the ACCURE-UK 2 trial with an identical protocol to 2 excluded owing to protocol 2 excluded owing to protocol
improve recruitment and increase the statistical power violation in eligibility* violation in eligibility*
to 90%. The recruitment target was revised to 244 patients,
with the aim of analysing 218 patients (109 per study
99 assigned to undergo appendicectomy 98 assigned to continue standard
group). However, owing to the COVID-19 pandemic and continue standard medical therapy medical therapy alone
pressures, the trial required a prolonged recruitment
period and enrolment was closed in Sept 29, 2022.
4 protocol violations
Prespecified outcomes14 and analyses are provided in 4 had disease relapse and
the appendix (pp 72–80). The demographic and clinical were re-baselined
characteristics of the patients at baseline were
summarised descriptively. All primary analyses (primary
96 underwent appendicectomy 93 received maintenance therapy
and secondary outcomes) were done on an intention-to- 3 did not undergo appendicectomy 5 did not receive standard medical
treat principle. χ² test of two proportions was used to 1 declined for personal reasons therapy
1 had disease relapse and declined 2 discontinued (side effects)
compare relapse rates between the appendicectomy and 1 had disease relapse and met trial 1 did not start
control group, reported with relative risk (RR) and exclusion criteria 2 unknown
corresponding 95% CIs. Logistic regression on the 1-year
relapse rate was used to adjust for disease extent as the
99 included in the intention-to-treat 98 included in the intention-to-treat
stratification factor during randomisation to obtain and pragmatic intention-to-treat and pragmatic intention-to-treat
correct variance estimates and explore the interaction analyses† analyses†
between treatment and disease extent, and to adjust for
age at time of randomisation, sex, current smoker, Figure 1: Trial profile
disease extent, time between start of most recent *Three patients were excluded because of active disease (two in appendicectomy group and one in the control group)
and one patient in the control group was excluded due to receiving biological agents at the time of randomisation.
disease exacerbation and randomisation. In addition,
†In the pragmatic intention-to-treat analysis, the same patients and allocation groups were used as in the
the interaction between treatment and country intention-to-treat analysis, with the distinction in the relapse outcome of the re-baselined patients during the
(the Netherlands vs the UK) was exploratively addressed. waiting period for appendicectomy.

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assessment and Akaike’s information criterion values. minimum correlation of at least 0·30 regarded as
Covariance structures evaluated included unstructured, acceptable.23–25
auto­regressive 1, Toeplitz matrix, and compound Safety data were reported by treatment group and
symmetry. The cohort-specific minimum clinically analysed based on the treatment actually received
important difference in the IBDQ was determined to (as-treated analysis), with absolute risk differences (ARD)
assess the clinical relevance of differences in the IBDQ, and corresponding 95% CIs.
by using a clinical anchor-based method calculating the No adjustments were made for multiplicity in secondary
difference in IBDQ change scores from baseline between outcome analyses, and these should be considered
patients responding yes or no to the global change exploratory. Missing outcome data were not imputed
question. The correlation coefficient between the IBDQ (appendix p 16). All statistical tests were two-sided and
change score and the global change question was p values less than 0·05 were considered statistically
calculated by Pearson’s correlation method, with a significant. Additional details of the statistical methods
were published and listed in the appendix (pp 8–9).14 Data
Appendicectomy Control group were analysed with SPSS (version 28.0.1.1) and Stata
group (n=99) (n=98) (version 17.0). All outcomes and statistical methods
Age, years 42·2 (12·5) 43·2 (13·0) presented in this Article were prespecified in the study
Age at diagnosis, years 33·7 (11·0) 35·5 (12·6) protocol and corresponding statistical analysis plan.
Sex Additionally, a post-hoc sensitivity analysis of the primary
Female 56 (57%) 55 (56%) outcome was done, limited to patients with available
Male 43 (43%) 43 (44%) endoscopic follow-up data.
Disease duration, years* 5·1 (1·8–11·6) 5·3 (1·8–11.3) The patient safety and trial evaluation were monitored
Smoking status by an independent data monitoring and safety committee
Current smoker 14 (14%) 12 (12%) (appendix p 5).
Former smoker 39 (39%) 47 (48%)
BMI, kg/m²† 24·3 (3·4) 24·8 (3·7) Role of the funding source
Classification of physical status‡ of more than category ASAII 0 1 (1%) The funders of the study had no role in study design,
Primary sclerosing cholangitis† 1 (1%) 0
data collection, data analysis, data interpretation, writing
Family history of inflammatory bowel disease† 24 (24%) 30 (31%)
of the report.
Medication at baseline
No medication 9 (9%) 4 (4%)
Results
Between Sept 20, 2012, and Sept 21, 2022, 1386 patients
Topical therapy 23 (23%) 22 (22%)
were assessed for eligibility, of whom 201 were randomly
Oral mesalazine 76 (77%) 81 (83%)
assigned to the appendicectomy group (n=101) or the
Systemic steroids 1 (1%) 1 (1%)
control group (n=100). After exclusion of four patients
Immunomodulators 6 (6%) 12 (12%)
due to protocol violation in eligibility (three had active
Extent of disease§
disease and one received biological agents at time of
Proctitis, E1 38 (38%) 39 (40%)
randomisation), 99 patients in the appendicectomy group
Left-sided colitis, E2 34 (34%) 36 (37%)
and 98 patients in the control group were included in
Pancolitis, E3 27 (27%) 23 (23%)
the intention-to-treat and pragmatic intention-to-treat
Time from start of most recent exacerbation ulcerative colitis 30·7 (17·9) 32·0 (19·4)
analyses (figure 1). Of the total participants, 168 were
before randomisation, weeks†
enrolled in the Dutch trial arm (which also included
Partial Mayo score
two participants from the Irish site) and 29 in the
0 73 (74%) 77 (79%)
ACCURE-UK trial 2 arm. The demographics and clinical
1 24 (24%) 17 (17%)
characteristics of the patients were similar across the
2 4 (4%) 2 (2%)
groups at baseline (table). Mean age was 42·2 years
Total Mayo score
(SD 12·5) in the appendicectomy group and 43·2 years
0 32 (41%), n=79 44 (51%), n=86
(SD 13·0) in the control group. 56 (57%) of 99 participants
1 38 (48%), n=79 31 (36%), n=86
in the in the appendicectomy group and 55 (56%) of 98
2 9 (11%), n=79 11 (13%), n=86
in the control group were women. Most patients
Endoscopic subscore=1 33 (42%), n=79 31 (36%), n=86
(76 [77%] of 99 in the appendicectomy group and
Data are mean (SD), n (%), or median (IQR). *Disease duration is the time since diagnosis of ulcerative colitis to 81 [83%] of 98 in the control group) were using oral
randomisation. †Data were missing for one patient in the control group for BMI; for 27 patients in the appendicectomy mesalazine as maintenance therapy. Seven (7%) patients
group and 32 in the control group for primary sclerosing cholangitis; for one patient in the appendicectomy group for
in the appendicectomy group and two (2%) patients in
family history of inflammatory bowel disease; and for five patients in the appendicectomy group and two in the control
group for most recent exacerbation of ulcerative colitis. ‡Classification of physical status according to the American the control group had previously used biological therapy
Society of Anesthesiologists. §According to Montreal classification. for their most recent exacerbation, but only more than
3 months before random­ isation; median time to
Table: Baseline demographic and disease characteristics (intention-to-treat population)
appendicectomy was 2·0 months (IQR 1·0–3·0).

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Six (6%) patients in the appendicectomy group had a 100

relapse during the waiting period for appendic­ectomy. 90
Among these, four patients were treated to complete
80
remission (ie, re-baselined) and sub­sequently under­went RR 0·65 (95% CI 0·47–0·89);

Proportion of patients (%)

70 p=0·005; adjusted p=0·002*
appendicectomy, one patient achieved remission but
60
opted to not have an appendic­ectomy, and one patient
started a biological agent and therefore met the 50 55 (56%) of 98

trial’s exclusion criteria and became ineligible for 40

appendicectomy. Additionally, one patient declined 30 36 (36%) of 99
appendic­ectomy after random­isation. Thus, three patients 20
in the appendic­ectomy group ultimately did not undergo 10
appendicectomy. 0
At 1 year, the relapse rate was significantly lower in the Control Appendicectomy
appendicectomy group than in the control group Figure 2: Primary outcome result
(36 [36%] of 99 patients vs 55 [56%] of 98 patients; *Adjusted for age, sex, current smoking, disease extent, and weeks since most
RR 0·65 [95% CI 0·47–0·89]; p=0·005; adjusted recent exacerbation.
p=0·002; figure 2). Two of the 63 patients who remained
in remission after appendicectomy had a relapse during over time. The total IBDQ score and IBDQ bowel
the waiting period and were re-baselined. When symptoms domain score significantly differed over time
considering these two patients as relapses in the prag­ between the groups in favour of the appendicectomy
matic intention-to-treat analysis, the results were similar group (total IBDQ score: MD 3·80 [95% CI 1·20–6·40],
(38 [38%] of 99 patients vs 55 [56%] of 98 patients; p=0·005; IBDQ bowel symptoms domain score: MD 0·16
RR 0·68 [95% CI 0·50–0·93]; p=0·01). For details of [95% CI 0·06–0·25], p=0·002), with, at 12 months, a
other prespecified analysis for the primary outcome and mean total IBDQ score difference between the groups of
for the post-hoc sensitivity analysis see the appendix 6·4 points (95% CI 2·3–15·0). The mean total IBDQ score
(pp 12, 17). change between the groups was in favour of the
In the appendicectomy group, 29 (81%) of 36 relapsed appendicectomy group, with a mean difference between
patients had one relapse each and seven (19%) had the groups of 11 points (95% CI 2·6–19·6; p=0·01). There
two relapses each, whereas in the control group, were no significant differences in the other IBDQ
38 (69%) of 55 relapsed patients had one relapse each, subdomains. The minimum clinically important
12 (22%) patients had two relapses each, and difference was calculated as 17·8 point change in IBDQ
five (9%) patients had three relapses each (RR 0·85 score (95% CI 5·8–29·9). Comprehensive analyses of
[95% CI 0·59–1·24]; p=0·40). Median time-to-first secondary outcomes and missing secondary endpoint
relapse was not reached in the appendicectomy group data are summarised in the appendix (pp 13–16).
and was 50·57 weeks (95% CI 37·59–63·56) in the Postoperative complications occurred in five (5%) of
control group (hazard ratio for relapse 0·54 [95% CI 96 patients who underwent appendicectomy, of which
0·36–0·82]; p=0·003; figure 3A). Disease activity over the two (2%) were classified as major and reported as serious
trial period showed increases in the total and partial adverse event. One patient had an internal herniation
Mayo scored in both groups, with the appendicectomy requiring laparotomy and another had an intra-
group showing a lower total mayo score at 12 months abdominal haematoma that was successfully drained.
(mean 1·2 points [SD 1·8]) compared with the control Both patients remained in remission during follow-up.
group (1·8 points [SD 2·3]; MD 0·70 [95% CI 0·11–1·29]; No serious adverse events were reported in the control
p=0·02). There were no colectomies done during the group (ARD 2·1% [95% CI –0·77 to 4·9]; p=0·24).
12-month follow-up period. Adverse events were reported in 11 (11%) of 96 patients in
Medication use during the trial period is shown in the appendicectomy group and in 10 (10%) of 101 patients
figure 4. Biological agents were initiated less frequently in in the control group (ARD 1·6% [95% CI –7·1 to 10·2];
the appendicectomy group than in the control group over p=0·72). The most frequently reported adverse events
the trial follow-up period (OR 0·003 [95% CI 0·00–0·27]; were postoperative temporary self-limiting abdominal
p=0·01). Both groups showed significantly decreasing use pain, which occurred in three (3%) patients in the
of oral mesalazine (OR 0·82 [95% CI 0·69–0·97]; p=0·02) appendicectomy group, and skin rash, reported in
over the trial period. At 12 months, for those with available three (3%) patients in the control group. Two cases (2%)
data, 58 (62%) of 94 patients in the appendicectomy group of low-grade appendiceal mucinous neoplasm were
and 73 (80%) of 91 patients in the control group used incidentally found in resected appendix specimens in
mesalazine that there were no other significant changes the appendicectomy group and did not require further
in medication use in the study. treatment. Safety and postoperative complication
The EQ-5D-3L utility score and the EORTC QLQ-C30 out­comes are listed in the appendix (p 17). There were
scores showed no significant between-group differences no deaths reported in either group.

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A
99 (0)
100 Appendicectomy
98 (0) 88 (0) Control
90
76 (0)
80 70 (2)
75 (0) 65 (27)
70
Relapse-free survival (%)

34 (32)
60 64 (0)

55 (1)
50
46 (33) 10 (9)
40

30

20

10
HR 0·54 (95% Cl 0·36–0·82); p=0·003
0
0 13 26 39 52 65
Time from randomisation to clinical relapse or end of study (weeks)

B Health-related quality of life outcomes over time

1·00 100
90
80
0·75
70
EQ-5D-3L utility score

EORTC QLQ-C30 score

60
0·50 50
40
30
0·25
20
Appendicectomy
10
Control
0 0
Baseline 3 months 6 months 9 months 12 months
248 Time (months)
224 * * * *

200
176
Total IBDQ score

152
128
104
Figure 3: Secondary outcome
results 80
(A) Kaplan–Meier survival 56
analysis with log-rank testing.
32
Kaplan–Meier plot with log-
rank testing comparing the 0
Baseline 3 months 6 months 9 months 12 months
time-to-first-relapse following
randomisation between the Time (months)
appendicectomy and control
Bowel symptoms Systemic symptoms Social function Emotional function
groups. Hazard rate is
unadjusted for age, sex, current 7
* * * *
smoking, disease extent, 6
and weeks since most recent
5
IBDQ subscale

exacerbation. Data at each

timepoint are number at 4
risk (number censored). 3
(B) Health-related quality-of-
life outcomes over time. 2
EQ-5D-3L=EQ-5D 3-level. 1
IBDQ=Inflammatory Bowel Control Appendicectomy Control Appendicectomy Control Appendicectomy Control Appendicectomy Control Appendicectomy
0
Disease Questionnaire. Baseline 3 months 6 months 9 months 12 months
*p<0·05 in generalised linear Time (months)
mixed models.

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A None B Topical therapy

100 Appendicectomy 100
90 Control 90
80 80
Proportion of patients (%)

70 70
60 60
50 50
40 40
30 30
20 20
10 10
0 0

C Oral mesalazine D Systemic steroid

100 100
90 90
80 80
Proportion of patients (%)

70 70
60 60
50 50
40 40
30 30
20 20
10 10
0 0

E Immunomodulators F Biological agents

100 100
90 90
80 80
Proportion of patients (%)

70 70
60 60
50 50
40 40
30 30
20 20
10 10 p=0·01 p=0·01 p=0·01 p=0·01
0 0
Baseline 3 months 6 months 9 months 12 months Baseline 3 months 6 months 9 months 12 months
Time (months) Time (months)

Figure 4: Medication use

(A) None. (B) Topical therapy, defined as rectal enemas or suppositories. (C) Oral mesalazine. (D) Systemic steroid, as oral corticosteroids (prednisone or equivalents or
budesonide). (E) Immunomodulators (ie, azathioprine, methotrexate, thioguanine). (F) Biological agents, such as biological medication (anti-TNF, integrin antibody,
or small molecules such as JAK inhibitors). In the generalised estimating equation, the baseline measurement was included as a fixed effect to adjust for initial
differences between groups. Data for medication use were available for 97 patients in the appendicectomy group and 93 in the control group at 3 months; 89 and 90,
respectively, at 6 months; 91 and 87, respectively, at 9 months; and 94 and 91, respectively, at 12 months.

Discussion 0·47–0·89]) suggests that appendicectomy might be a

This randomised controlled trial showed that appendic­ viable additional therapeutic option for maintaining
ectomy was superior to medical therapy alone in remission in ulcerative colitis. Furthermore, patients
maintaining remission in patients with ulcerative colitis who underwent appendicectomy were significantly more
within 1 year. At 12 months, around a third of the patients likely to maintain lower disease activity, reduce the
in the appendicectomy group had a relapse compared initiation of biological agents, and improve health-related
with more than half of those in the control group. This quality of life compared with patients who received
significant relative risk reduction (RR 0·65 [95% CI standard medical therapy alone at 1 year.

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The relapse rates in the trial were higher in both groups costs for ulcerative colitis, primarily driven by the
than initially expected, and several factors might have increased use of biological agents.31 Another advantage of
contributed to this difference. First, the protocol was a surgical procedure as therapeutic inter­vention is that
amended to include patients on immunomodulators, non-adherence is not a factor, making it a more attractive
who exhibit higher relapse rates26 than the reported alternative to medication or main­ten­ance medication for a
37% in patients on oral mesalazine within 1 year.27 subset of patients.
Second, the efficacy–effectiveness gap, reflecting Moreover, the appendicectomy group showed a
differences between outcomes in clinical trials and real- beneficial effect on some health-related quality-of-life
world practice, might also have had an effect on these out­comes. This might be a result of the lower relapse
relapse rates. This pragmatic trial more closely resembles rates in this group, as active colitis is associated with an
real-world practice, by maintaining standard medical impaired health-related quality of life.4–6 The difference
therapy at the discretion of the treating gastroenterologist was primarily observed regarding bowel symptoms,
in both groups, rather than enforcing standardised although the difference between the groups in the
medication. This approach, combined with the potential IBDQ change from baseline to 12 months did not meet
issue of non-adherence to main­tenance therapy, a known the calculated minimum clinically important difference.
risk factor for relapse,28,29 might con­sequently explain the The lack of significant differences in EQ-5D-3L utility
higher relapse rates observed. and EORTC QLQ-C30 scores between the groups might
Previous studies on the role of appendicectomy in be due to lower sensitivity and weaker correlation of
ulcerative colitis have suggested a potential beneficial these measures with disease relapse compared with
effect on the disease course, but were limited by their the total IBDQ score. Given the nature of the
observational, uncontrolled designs.11,12 The current EQ-5D-3L questions, patients experiencing relapse are
randomised controlled trial provides more solid evidence more likely to report worse scores in the dimensions of
confirming these preliminary observations, and supports usual activities, pain or discomfort and anxiety or
the theory that the appendix has an immunomodulatory depression, but not in mobility or self-care.
role in ulcerative colitis.9,10 The appendix is known to be a Limitations of this trial were the absence of a
reservoir for commensal gut bacteria and gut-associated sham-surgery control group to determine the contribution
lymphoid tissue, both having an important role in the of the placebo effect, which might have biased some of the
gastrointestinal tract’s immune response. In ulcerative health-related quality-of-life read outs, and the long
colitis, the dysregulated immune system leads to chronic duration of the trial, which might compromise the external
colonic inflammation. One possible mechanism is that validity. Nonetheless, this pragmatic trial was done across
the appendix contributes to the maintenance and 21 international sites, enhancing its external validity.
activation of immune cells, especially CD4 T helper cells, Participation bias might have been introduced, as it is
that drive the inflammatory process. By removing the likely that only a subset of patients who were in remission
appendix, these immune cells might be diminished, were willing to partici­pate in a randomised surgical trial
thereby reducing the inflammatory mucosal activation to undergo an additional appendicectomy. With the
and leading to a reduced relapse rate. Nevertheless, this publication of beneficial results of appendicectomy trials,
trial primarily focused on clinical outcomes, and did not patient self-preference patterns might have been
evaluate the appendix’s immunomodulatory mechanism, influenced. Finally, in this pragmatic trial, not all patients
so no further causal conclusions can be drawn. Further underwent follow-up endoscopy to objectively determine
studies are needed to elucidate the immunological the relapse rate. Since a per-protocol analysis was not
mechanisms of the appendix in ulcerative colitis and prespecified in the statistical analysis plan, these data are
ongoing follow-up of this trial will inform longer term not presented here. However, the incidences of relapse
outcomes. Further research should also focus on were similar between both groups, and a similar difference
identifying patients who are most likely to benefit. between the groups was observed (appendix p 17).
The appendicectomy group not only had lower relapse In conclusion, appendicectomy is a viable and safe
rates but also showed favourable trends in medication strategy for reducing the relapse rate in patients with
use. Biological agents were initiated less frequently in the ulcerative colitis compared with standard medical
appendicectomy group than in the control group, with the therapy at 1 year, offering a potential addition to standard
largest difference observed at 6 months (0·0% vs 4·4%, medical therapies.
respectively). By 12 months, however, this difference had The ACCURE Study Group
narrowed (3·2% vs 5·5%), suggesting that appendicectomy Executive writing group—*Eva Visser MD (Department of Surgery,
may delay the need for biologic therapy. If this trend were Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands),
Prof Thomas D Pinkney MD (Department of Surgery, University Hospitals
to persist beyond 12 months, even a modest reduction in Birmingham, Birmingham, UK), Prof Marcel G W Dijkgraaf PhD
biologic use could be clinically and economically (Epidemiology and Data Science, Amsterdam UMC, Amsterdam,
meaningful. These findings should be interpreted with Netherlands), Prof Willem A Bemelman PhD (Department of Surgery,
caution, as these patient numbers are small.30 Pillai and Amsterdam UMC, University of Amsterdam, Amsterdam,
Netherlands), Prof Geert R D’Haens PhD (Department of
colleagues reported a 10% annual increase in health-care

558 www.thelancet.com/gastrohep Vol 10 June 2025

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Gastroenterology, Amsterdam UMC, Amsterdam, Netherlands), Amsterdam UMC, Amsterdam, Netherlands) Pieter C F Stokkers
Christianne J Buskens PhD (Department of Surgery, Amsterdam UMC, (Department of Gastroenterology, Onze Lieve Vrouwe Gasthuis -
University of Amsterdam, Amsterdam, Netherlands). *First author. Locatie West, Amsterdam, Netherlands), Malaika S Vlug
Study group—Yair I Z Acherman (Department of Surgery, Spaarne (Department of Surgery, Amsterdam UMC, Amsterdam,
Gasthuis, Amsterdam, Netherlands), Prof Naila Arebi (Department Netherlands), Bart C Vrouenraets (Department of Surgery,
of Department of Gastroenterology, St Mark’s Hospital, London, UK), Onze Lieve Vrouwe Gasthuis - Locatie West, Amsterdam, Netherlands),
Elizabeth Arthurs (Department of Gastroenterology, Bristol Royal Rachel West (Department of Gastroenterology, Sint Franciscus Gasthuis,
Infirmary, Bristol, UK), Jarmila D W van der Bilt (Department of Surgery, Rotterdam, Netherlands), Jimme K Wiggers (Department of Surgery,
Flevoziekenhuis, Almere, Netherlands), Henri Braat (Department of Amsterdam UMC, Amsterdam, Netherlands), Manon E Wildenberg
Gastroenterology, Medisch Spectrum Twente, Twente, Netherlands), (Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC,
Menno A Brink (Department of Gastroenterology, Meander Medical Amsterdam, Netherlands), Prof Des Winter (Department of Surgery,
Centre, Amersfoort, Netherlands), Prof Matthew Brookes (Department of St Vincent’s University Hospital, Dublin, Ireland), Nuha A Yassin
Gastroenterology, New Cross Hospital Royal Wolverhampton NHS Trust, (Department of Surgery, New Cross Hospital Royal Wolverhampton
Wolverhampton, UK), James P Y Brown (Clinical Research Unit, NHS Trust, Wolverhampton, UK), Esmerij P M van der Zanden
University of Birmingham, Birmingham, UK), Prof Steven R Brown (Department of Gastroenterology, Amstelland Hospital, Amstelveen,
(Department of Surgery, University of Sheffield, Sheffield, UK), Netherlands). A detailed list of trial sites and investigators are in the
Prof Esther C J Consten (Department of Surgery, Meander Medical appendix (p 4).
Centre, Amersfoort, Netherlands), Rachel Cooney (Department of
Contributors
Gastroenterology, University Hospitals Birmingham, Birmingham, UK),
WAB, JPYB, CJB, GRD’H, EJE, ODF, THI, MK, LM, SP, TDP, CYP,
Rogier M P H Crolla (Department of Surgery, Amphia Hospital, Breda,
and BS contributed to the conceptualisation of the study. WAB, JPYB,
Netherlands), Richard J Davies (Department of Surgery, Addenbrooke’s
GRD’H, MGWD, EJE, ODF, KH, LH, THI, MK, LM, SP, CYP, SS, BS,
Hospital, Cambridge University Hospitals NHS Trust and University of
MES, and EV curated the data. MGWD and EV did the formal analysis.
Cambridge, Cambridge, UK), Annekatrien C T M Depla (Department
CJB and TDP provided funding acquisition. YIZA, NA, EA, WAB,
of Gastroenterology, Slotervaart Hospital, Amsterdam, Netherlands),
JDWvdB, HB, MAB, MB, JPYB, SRB, CJB, ECJC, RC, RMPHC, RJD,
Prof Glen Doherty (Department of Gastroenterology, St Vincent’s
ACTMD, GRD’H, GD, PvD, MD, EJE, JPE, ODF, SCMF, MFG, JG,
University Hospital, Dublin, Ireland), Peter van Duijvendijk
CEG, LH, RH, THI, JJ, MK, LM, RCM-H, GHHM, GM, GAN, SP,
(Department of Surgery, Gelre Hospital, Apeldoorn, Netherlands),
EGJMP, TDP, CYP, TR, IR, SS, JPS, TCJS, JS, SMS, BS, MES, PCFS,
Marjolijn Duijvestein (Department of Gastroenterology, Radboud
EV, MSV, BCV, RW, JKW, MEW, DW, NY, and EPMvdZ conducted the
University Medical Centre, Nijmegen, Netherlands), Emma J Eshuis
investigation. WAB, CJB, GRD’H, MGWD, EJE, ODF, KH, THI, MK,
(Department of Gastroenterology, Ter Gooi Hospital, Hilversum,
LM, SP, TDP, CYP, and BS contributed to the study’s methodology.
Netherlands), Jonathan P Evans (Department of Surgery, Queen’s
YIZA, NA, EA, WAB, JDWvdB, HB, MAB, MB, JPYB, SRB, CJB, ECJC,
Medical Centre, Nottingham, UK), Prof Omar D Faiz (Department
RC, RMPHC, RJD, ACTMD, GRD’H, GD, PvD, MD, EJE, JPE, ODF,
of Surgery, St Mark’s Hospital, London, UK), Steven C M Fong
SCMF, MFG, JG, CEG, LH, RH, THI, JJ, MK, LM, RCM-H, GHHM,
(Department of Gastroenterology, Conquest Hospital,
GM, GAN, SP, EGJMP, TDP, CYP, TR, IR, SS, JPS, TCJS, JS, SMS, BS,
St Leonards-on-Sea, UK), Michael F Gerhards (Department of Surgery,
MES, PCFS, EV, BCV, RW, DW, NY, and EPMvdZ carried out project
Onze Lieve Vrouwe Gasthuis - Locatie Oost, Amsterdam, Netherlands),
administration. MGWD and KH developed the software. WAB, JPYB,
Jennie Grainger (Department of Surgery, Countess of Chester Hospital,
CJB, GRD’H, EJE, ODF, THI, MK, LM, SP, TDP, CYP, BS, and
Chester, UK), Caris E Grimes (Department of Surgery, Medway
MEW provided the resources. WAB, JPYB, CJB, GRD’H, MGWD, MD,
Maritime Hospital, Gillingham, UK), Kelly Handley (Birmingham
ODF, RH, THI, MK, SP, TDP, CYP, and BS supervised the project.
Clinical Trials Unit, University of Birmingham, Birmingham, UK),
WAB, JDWvdB, HB, MAB, MB, JPYB, SRB, CJB, ECJC, RC, RMPHC,
Lianne Heuthorst (Department of Surgery, Amsterdam UMC,
RJD, ACTMD, GRD’H, MGWD, GD, PvD, EJE, JPE, SCMF, MFG, JG,
Amsterdam, Netherlands), Roel Hompes (Department of Surgery,
CEG, KH, RH, THI, JJ, MK, LM, RCM-H, GHHM, GM, GAN, SP,
Amsterdam UMC, Amsterdam, Netherlands), Prof Tariq H Iqbal
EGJMP, TDP, CYP, TR, IR, JPS, TCJS, JS, SMS, PCFS, EV, BCV, RW,
(Department of Gastroenterology, University Hospitals Birmingham,
DW, NY, and EPMvdZ were responsible for validation of the data.
Birmingham, UK), Jeroen Jansen (Department of Gastroenterology,
EV was responsible for visualisation and writing of the original draft.
Onze Lieve Vrouwe Gasthuis - Locatie Oost, Amsterdam, Netherlands),
YIZA, NA, WAB, JDWvdB, HB, MAB, MB, JPYB, SRB, CJB, ECJC, RC,
Manjinder Kaur (Birmingham Clinical Trials Unit, University of
RMPHC, RJD, ACTMD, GRD’H, MGWD, GD, PvD, MD, EJE, JPE,
Birmingham, Birmingham, UK), Laura Magill (Clinical Research Unit,
ODF, SCMF, MFG, JG, CEG, KH, LH, RH, THI, JJ, MK, LM, RCM-H,
University of Birmingham, Birmingham, UK), Rosalie C Mallant-Hent
GHHM, GM, GAN, SP, EGJMP, TDP, CYP, TR, IR, SS, JPS, TCJS, JS,
(Department of Gastroenterology, Flevoziekenhuis, Almere,
SMS, BS, MES, PCFS, MSV, BCV, RW, JKW, MEW, DW, NY, and
Netherlands), Prof Guido H H Mannaerts (Department of Surgery,
EPMvdZ reviewed and edited of the manuscript. All authors contributed
Sint Franciscus Gasthuis, Rotterdam, Netherlands), Prof Gordon Moran
substantially to the interpretation of data for the work, reviewed the
(Department of Gastroenterology, Queen’s Medical Centre, Nottingham,
manuscript critically for important intellectual content, approved
UK), Gary A Nicholson (Department of Surgery, Queen Elizabeth
the final version of the manuscript to be published, and agreed to be
University Hospital, Glasgow, UK), Shri Pathmakanthan (Department of
accountable for all aspects of the work in ensuring that questions
Gastroenterology, University Hospitals Birmingham, Birmingham, UK),
related to the accuracy or integrity of any part of the work are
Engelbertus G J M Pierik (Department of Surgery, Isala Hospital, Zwolle,
appropriately investigated and resolved. EV, CJB, MGWD, and
Netherlands), Prof Cyriel Y Ponsioen (Department of Gastroenterology,
TDP had directly accessed and verified the underlying data reported
Amsterdam UMC, Amsterdam, Netherlands), Tim Raine (Department
in the manuscript.
of Gastroenterology, Addenbrooke’s Hospital, Cambridge, UK),
Ian Reilly (Department of Gastroenterology, Countess of Chester Declaration of interests
Hospital, Chester, UK), Saloomeh Sahami (Department of Surgery, NA reports receiving consulting fees from Pfizer; presentation fees
Amsterdam UMC, Amsterdam, Netherlands), John Paul Seenan from Pfizer, Lilly, Takeda, and AbbVie; and travel support from Tillotts
(Department of Gastroenterology, Queen Elizabeth University Hospital, Pharma. WAB reports received speaker fees from Applied Medical and
Glasgow, UK), Tom C J Seerden (Department of Gastroenterology, Johnson & Johnson. JPYB reports receiving funding from the National
Amphia Hospital, Breda, Netherlands), Jamshed Shabbir (Department Institute for Health and Social Care Research (NIHR) Efficacy and
of Surgery, Bristol Royal Infirmary, Bristol, UK), Simon M. Shaw Mechanism Evaluation (EME) programme for the conduct of the
(Department of Surgery, Conquest Hospital, St. Leonards-on-Sea, ACCURE-UK 2 study, the UK part of the ACCURE trial. CJB reports
UK), Baljit Singh (Department of Gastroenterology, receiving funding from Nuts-Ohra (FNO 1202–008), the Netherlands
Onze Lieve Vrouwe Gasthuis - Locatie West, Amsterdam, part of the ACCURE trial; and received speakers fees from Takeda,
Netherlands), Merle E Stellingwerf (Department of Surgery, Janssen, and Tillotts Pharma. RC reports receiving speaker fees from

www.thelancet.com/gastrohep Vol 10 June 2025 559

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Takeda, Falk, Lilly, AbbVie, and Galapagos; and travel support from Acknowledgments
AMC Amsterdam to attend the ACCURE meeting. RMPHC reports This study was funded by Nuts-Ohra (FNO 1202–008) in the Netherlands
serving as a proctor for Intuitive Surgical. RJD reports serving as the and the NIHR EME project (16/61/35) in the UK. We thank the patients
current chair of the data monitoring and ethics committee for the and trial site staff members for their involvement and contributions to
NIHR funded MEErKAT trial in the UK. GRD’H reports receiving this trial; the members of the UK Trial Steering Committee (Neil Smart,
grants from Pfizer, Takeda, AbbVie, Eli Lilly, BMS, and Alimentiv; Brian Cooper, Apostolos Fakis, Sue Blackwell) for their oversight
consulting fees from AbbVie, Agomab, Alimentiv, AstraZeneca, Bristol- of the trial; the members of the data safety monitoring board
Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom (Mark J W Koelemaij, Tom M Karsten, Jan H M van den Brande,
Biosciences, Index Pharmaceuticals, GlaxoSmithKline, Pfizer, Johnson and Kerry Hood) for their oversight and guidance; the staff at the
& Johnson, Polpharma, Procise Diagnostics, Prometheus Laboratories, University of Birmingham Clinical Trials Unit (Ruth Evans,
Prometheus Biosciences, and Ventyx; payment for lectures from Erum Khan, Kelly Handley, Hannah Summers, Anthony Prigg, and
AbbVie, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Hardeep Sandhar) for their support in trial management; and the
Eli Lilly, Johnson & Johnson, Pfizer, and Takeda; and travel support gastroenterologists, surgeons, physicians and research staff members
from Eli Lilly and Pfizer; and participation on data safety monitoring who have contributed to the success of this trial.
boards or advisory boards for Galapagos, AstraZeneca, and Seres
References
Health. MD reports receiving grants from Galapogos–Alfasigma, Pfizer,
1 Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet
Bristol Myers Squibb, Janssen, Celltrion, and Takeda; and received 2023; 402: 571–84.
consulting fees from AbbVie, Galapagos–Alfasigma, Bristol Myers
2 Kaplan GG. The global burden of IBD: from 2015 to 2025.
Squibb, Janssen, Celltrion and Takeda; and received speakers fees from Nat Rev Gastroenterol Hepatol 2015; 12: 720–27.
Bristol Myers Squibb, Galapagos–Alfasigma, Takeda, Janssen,
3 Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and
and Dr Falk. GD reports receiving grants from MSD, Pfizer, Janssen, prevalence of inflammatory bowel disease in the 21st century:
AbbVie, Abbott, Takeda, Galapogos–Alfa Sigma, Eli Lilly, Celltrion a systematic review of population-based studies. Lancet 2017;
and Amgen; speakers honorarium from AbbVie, Dr Falk, and Takeda. 390: 2769–78.
SCMF reports receiving speakers fee from Takeda, AbbVie, and Ferring; 4 Bernklev T, Jahnsen J, Lygren I, Henriksen M, Vatn M, Moum B.
received support for attendance at educational conferences from Tillotts Health-related quality of life in patients with inflammatory bowel
Pharma and Takeda. KH reports funding from the NIHR and the disease measured with the short form-36: psychometric
British Heart Foundation; and serves in unpaid roles on advisory boards assessments and a comparison with general population norms.
for King’s College London and the University of Oxford. GM reports Inflamm Bowel Dis 2005; 11: 909–18.
receiving investigator grants from AstraZeneca, Janssen, Bristol Myers 5 Nordin K, Påhlman L, Larsson K, Sundberg-Hjelm M, Lööf L.
Squibb, Alimentiv, and Pfizer; received consulting fees from Pfizer, Health-related quality of life and psychological distress in a
AbbVie, and Janssen; and honoraria for lectures and presentations from population-based sample of Swedish patients with
AbbVie and Takeda; serves on advisory boards for Pfizer, AbbVie, inflammatory bowel disease. Scand J Gastroenterol 2002; 37: 450–57.
and Janssen; provided consultancy services for Alimentiv and Satisfai 6 Reinisch W, Sandborn WJ, Bala M, et al. Response and remission
Health. TDP reports receiving grants from the NIHR for the are associated with improved quality of life, employment and
ROSSINI-Platform Trial, ROSSINI 2 Extension Trial, and OCEAN trial, disability status, hours worked, and productivity of patients with
ulcerative colitis. Inflamm Bowel Dis 2007; 13: 1135–40.
all of which are unrelated to this work; and received honoraria for
lectures from MSD. CYP reports receiving grants from Next Generation 7 Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on
the selecting therapeutic targets in inflammatory bowel disease
Medicines and Perspectum; received consulting fees from Chemomab;
(STRIDE) initiative of the international organization for the study
and payment for expert testimony from Nationale Nederlanden. of IBD (IOIBD): determining therapeutic goals for treat-to-target
TR reports receiving institutional grants from AbbVie and Takeda; strategies in IBD. Gastroenterology 2021; 160: 1570–83.
received consulting fees from AbbVie, AstraZeneca, Boehringer- 8 Raine T, Bonovas S, Burisch J, et al. ECCO guidelines on therapeutics
Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring, Galapagos, Gilead, in ulcerative colitis: medical treatment. J Crohns Colitis 2022; 16: 2–17.
GSK, Heptares, Janssen, MonteRosa, MSD, Novartis, Numab, Pfizer, 9 Arjomand Fard N, Armstrong H, Perry T, Wine E. Appendix and
Roche, Sandoz, Takeda, Union Chimique Belge, and XAP Therapeutics; ulcerative colitis: a key to explaining the pathogenesis and directing
serves on the advisory board for Union Chimique Belge. IR reports novel therapies? Inflamm Bowel Dis 2023; 29: 151–60.
receiving support from Tillotts Pharma UK for attending meeting. 10 Sahami S, Kooij IA, Meijer SL, Van den Brink GR, Buskens CJ,
JPS reports receiving speaker fees from Pfizer, Alfasigma, Fresenius Te Velde AA. The link between the appendix and ulcerative colitis:
Kabi, AbbVie, Tillotts Pharma UK, Janssen-Cilag, Pharmacosmos UK, clinical relevance and potential immunological mechanisms.
Takeda UK, and Bristol-Myers Squibb; received support for attending Am J Gastroenterol 2016; 111: 163–69.
meetings and travel from AbbVie, Tillotts Pharma UK, Janssen-Cilag, 11 Bolin TD, Wong S, Crouch R, Engelman JL, Riordan SM.
and Celltrion; serves on advisory boards for Takeda, Galapagos, Dr Falk Appendicectomy as a therapy for ulcerative proctitis.
Pharma (UK), and AbbVie. BS reports being co-applicant on the Am J Gastroenterol 2009; 104: 2476–82.
NIHR grant for the UK part of the ACCURE trial, funded by the 12 Sahami S, Wildenberg ME, Koens L, et al. Appendectomy
EME programme; received consulting fees from WPA for an advisory for therapy-refractory ulcerative colitis results in pathological
role unrelated to this research; and received honoraria for lectures from improvement of colonic inflammation: short-term results of
Arthrex. RW reports receiving speaker fees from Pfizer, AbbVie, the PASSION study. J Crohns Colitis 2019; 13: 165–71.
and Ferring; and serves an unpaid role on the board of IBDREAM. 13 Gardenbroek TJ, Pinkney TD, Sahami S, et al. The ACCURE-trial:
MEW reports receiving research support from Boehringer Ingelheim the effect of appendectomy on the clinical course of ulcerative
and Hoffmann-LaRoche and a research contract from ExoBiologics. colitis, a randomised international multicenter trial (NTR2883)
and the ACCURE-UK trial: a randomised external pilot trial
All other authors declare no competing interests.
(ISRCTN56523019). BMC Surg 2015; 15: 30.
Data sharing 14 Visser E, Heuthorst L, Pathmakanthan S, et al. Clinical statistical
Data collected for this study, including deidentified individual participant analysis plan for the ACCURE trial: the effect of appendectomy on
data, will be made available to others upon reasonable request. These the clinical course of ulcerative colitis, a randomised international
data are available after publication of primary and secondary analysis multicentre trial. Trials 2024; 25: 218.
with no specified end date. Access to the data will be granted to 15 World Medical Association. World Medical Association Declaration
researchers who provide a methodologically sound proposal. Proposals of Helsinki: ethical principles for medical research involving
should be directed to EV or CJB. To gain access, data requestors will be human subjects. JAMA 2013; 310: 2191–94.
required to sign a data sharing agreement, and the data will be provided 16 Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN,
after the proposal is approval and the data sharing agreement is signed. Ellenberg JH. Use of the noninvasive components of the Mayo
score to assess clinical response in ulcerative colitis.
The trial protocol and statistical analysis plan are available in the
Inflamm Bowel Dis 2008; 14: 1660–66.
appendix (pp 18–86).

560 www.thelancet.com/gastrohep Vol 10 June 2025

 Articles

17 Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated 24 LeBlanc K, Mosli MH, Parker CE, MacDonald JK. The impact
clinical, molecular and serological classification of inflammatory of biological interventions for ulcerative colitis on health-related
bowel disease: report of a Working Party of the 2005 Montreal quality of life. Cochrane Database Syst Rev 2015; 2015: CD008655.
World Congress of Gastroenterology. Can J Gastroenterol 2005; 25 Guyatt G, Mitchell A, Irvine EJ, et al. A new measure of health
19 (suppl A): 5A–36A. status for clinical trials in inflammatory bowel disease.
18 Lamers LM, Stalmeier PF, McDonnell J, Krabbe PF, Gastroenterology 1989; 96: 804–10.
van Busschbach JJ. Measuring the quality of life in economic 26 Timmer A, Patton PH, Chande N, McDonald JW, MacDonald JK.
evaluations: the Dutch EQ-5D tariff. Ned Tijdschr Geneeskd 2005; Azathioprine and 6-mercaptopurine for maintenance of remission
149: 1574–78. in ulcerative colitis. Cochrane Database Syst Rev 2016;
19 Aaronson NK, Ahmedzai S, Bergman B, et al. The European 2016: CD000478.
Organization for Research and Treatment of Cancer QLQ-C30: 27 Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK.
a quality-of-life instrument for use in international clinical trials Oral 5-aminosalicylic acid for maintenance of remission in
in oncology. J Natl Cancer Inst 1993; 85: 365–76. ulcerative colitis. Cochrane Database Syst Rev 2020; 8: CD000544.
20 Pallis AG, Mouzas IA, Vlachonikolis IG. The inflammatory bowel 28 Kane S, Huo D, Aikens J, Hanauer S. Medication nonadherence
disease questionnaire: a review of its national validation studies. and the outcomes of patients with quiescent ulcerative colitis.
Inflamm Bowel Dis 2004; 10: 261–69. Am J Med 2003; 114: 39–43.
21 Dindo D, Demartines N, Clavien PA. Classification of surgical 29 Higgins PD, Rubin DT, Kaulback K, Schoenfield PS, Kane SV.
complications: a new proposal with evaluation in a cohort of Systematic review: impact of non-adherence to 5-aminosalicylic acid
6336 patients and results of a survey. Ann Surg 2004; 240: 205–13. products on the frequency and cost of ulcerative colitis flares.
22 Stellingwerf ME, de Koning MA, Pinkney T, Bemelman WA, Aliment Pharmacol Ther 2009; 29: 247–57.
D’Haens GR, Buskens CJ. The risk of colectomy and colorectal 30 Burisch J, Zhao M, Odes S, et al. The cost of inflammatory bowel
cancer after appendectomy in patients with ulcerative colitis: disease in high-income settings: a Lancet Gastroenterology &
a systematic review and meta-analysis. J Crohns Colitis 2019; Hepatology Commission. Lancet Gastroenterol Hepatol 2023; 8: 458–92.
13: 309–18. 31 Pillai N, Dusheiko M, Maillard MH, et al. The evolution of health
23 Irvine EJ, Feagan B, Rochon J, et al. Quality of life: a valid and care utilisation and costs for inflammatory bowel disease over
reliable measure of therapeutic efficacy in the treatment of ten years. J Crohns Colitis 2019; 13: 744–54.
inflammatory bowel disease. Gastroenterology 1994; 106: 287–96.

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