TA888/Scope Consultation Comments
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Summary form

National Institute for Health and Care Excellence

Single Technology Appraisal (STA)

Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986]

Please note: Comments received in the course of consultations carried out by NICE are published in the interests of openness and transparency, and to promote understanding of how recommendations are developed. The comments are published as a record of the submissions that NICE has received, and are not endorsed by NICE, its officers or advisory committees.

Comment 1: the draft remit

Section Consultee/
Commentator		 Comments [sic] Action
Appropriateness AbbVie Yes. Thank you for your
comment. No action
needed.
British Society of
Gastroenterology		 Yes. Crohn’s disease continues to cause significant morbidity despite the
current medications available. Crohn’s is a serious and complex disease
that can have a lifelong debilitating impact on patients if remission is not
achieved.
The BSG guidelines recommend that “Crohn’s’ disease patients refractory
to immunomodulator therapy despite dose optimisation should be
considered for biological therapy. Choice between anti-TNF therapy,
ustekinumab and vedolizumab should be made on an individual basis,
considering patient preference, cost, likely adherence, safety data and
speed of response to the agent.”(1)
Despite well-defined pathways and updated British society of
gastroenterology guidelines, existing therapies have significant drawbacks,
highlighting a major unmet therapeutic need for people living with moderate
to severe Crohn’s disease. Specifically, primary failure of anti-TNF induction		 Thank you for your
comment. This
technology has been
referred to NICE as a
Single Technology
Appraisal. No action
needed.

National Institute for Health and Care Excellence

Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
therapy occurs in 19–58% of patients in clinical trials (2). Among patients
responsive to anti-TNF therapies, discontinuation due to secondary loss of
response occurs in 17 to 22% of patients and approximately 40% required
dose escalation to maintain treatment efficiency (3-4). Treatment failure is
even higher among patients undergoing second line TNF inhibitor therapy.
In a meta-analysis the proportion of patients have discontinued treatment
due to loss of response was 68-77% at 12 months and 82 -90% by the end
of year 2(3-4). Diminishing efficacy stems in part from immunogenicity and
the formation of antibodies against biologics (4).
Additional treatment options are urgently needed to help control disease
and allow patients to return to their usual activities and potentially avoid
surgery. As this disease often impact people during their early adulthood,
poorly controlled disease has a dramatic impact on their education, careers
and life opportunities.
Our understanding is that this application is for EAMS use and is not a full
application for NICE Technology Appraisal (similar to the ones previously
published for Vedolizumab and Ustekinumab). So, our comments should be
taken to be applicable only for EAMS use, until a full NICE Technology
Appraisal for Risankizumab takes place.
1. Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, et al.
British Society of Gastroenterology consensus guidelines on the
management of inflammatory bowel disease in adults. Gut. 2019.
2. Stidham R.W., Lee T.C., Higgins P.D., Deshpande A.R., Sussman D.A.,
Singal A.G., Elmunzer B.J., Saini S.D., Vijan S., Waljee A.K. Systematic
review with network meta-analysis: The efficacy of anti-TNF agents for the

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
treatment of Crohn’s disease. Aliment. Pharmacol. Ther. 2014;39:1349–
1362.
3. Gordon JP, McEwan PC, Maguire A, Sugrue DM, Puelles J.
Characterizing unmet medical need and the potential role of new biologic
treatment options in patients with ulcerative colitis and Crohn's disease: a
systematic review and clinician surveys. Eur J Gastroenterol Hepatol.
2015;27(7):804-12.
4. Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ,
et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with
active luminal Crohn's disease: a prospective, multicentre, cohort study.
Lancet Gastroenterol Hepatol. 2019;4(5):341-53
Wording British Society of
Gastroenterology		 The remit states ‘Clinical management depends on disease activity, site,
behaviour of disease, response to previous treatments, side-effect profiles
of treatments and extra-intestinal manifestations, such as uveitis and
arthritis’.
As patients with Crohn’s disease often need lifelong treatment and
symptoms can be debilitating treatment considerations also include speed
of action, long term safety, patient acceptability (e.g. frequency of dosage
and mode of delivery of the drug) as well as impact on other co-morbidities
e.g. cardiac or malignancy or psoriasis history.
Extraintestinal manifestations should also include skin manifestations.		 Thank you for your
comment. The scope
has been updated to
reflect these additional
considerations.
Crohn’s & Colitis
UK		 Yes. Currently, there are limited treatment options available in treating
moderate to severe Crohn’s disease. It is important that patients have the
widest possible options available to them, particularly given what we are
increasingly coming to understand in terms of the importance of
personalised treatments.		 Thank you for your
comment. No changes
to the scope needed.

National Institute for Health and Care Excellence

Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
Timing Issues AbbVie The timing of this appraisal is appropriate. Thank you for your
comment. No changes
to the scope needed.
British Society of
Gastroenterology		 Given the high primary and secondary non-response rate of our current
medications there is a large cohort of patients whose symptoms and
disease are not controlled by current treatment options. This appraisal is a
matter of urgency for these patients waiting for a new treatment option.
Going forward to have a greater option available will greatly help clinicians
trying to find the right option for the individual patient.		 Thank you for your
comment. No changes
to the scope needed..
Crohn’s and
Colitis UK		 In light of Covid-19 and elective recovery, there is a benefit to an additional
treatment option that can be administered at home to potentially reduce
infection risk and pressure on the NHS (outpatient appointments, day cases
and workforce).		 Thank you for your
comment. No changes
to the scope needed.
Tillotts Pharma
UK Ltd		 Low urgency. Existing therapies are well established and successful in
managing symptoms except in a small proportion of patients with moderate
to severe Crohn’s disease, where symptoms remain uncontrolled.		 Thank you for your
comment. No changes
to the scope needed.

Comment 2: the draft scope

Section Consultee/
Commentator		 Comments [sic] Action
Background
information		 British Society of
Gastroenterology		 Background information is accurate.
More information could be added on the proportion of patients who do not
respond to current treatment.		 Thank you for your
comment. The
background section of
the scope is intended to
provide a broad
overview of the disease

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
and its expected
management. It is
anticipated that the
proportion of people
who do not respond to
current treatment will be
discussed during the
appraisal. No changes
to the scope needed.
Crohn’s & Colitis
UK		 1 in 133 children and adults are living with Inflammatory Bowel Disease.
We would ask the Committee to revisit the description of the following
sentences: “Less common symptoms include fever, nausea, vomiting,
arthritis, inflammation and irritation of the eyes, mouth ulcers and areas of
painful, red and swollen skin.”
-
Remove less common
-
Refer to extra intestinal manifestations
People with IBD are affected by more than just their bowel symptoms. Up to
50% will experience extraintestinal manifestations, involving different parts
of their body, commonly joints, skin, bones, eyes, kidneys and liver.
In addition to the symptoms listed in the “Background” section, we would
like to see fatigue and anaemia included, as these are often overlooked, but
have a significant impact (IBD UK report Crohn’s and Colitis Care in the UK)
We would also strongly advocate for recognition within this section of the
debilitating impact of the condition on the daily lives and quality of life of
those affected, including its impact on mental health and wellbeing,
education, employment and relationships.		 Thank you for your
comment. The scope
has been updated to
reflect the comments
made around the
impact of the condition.

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
The symptoms of urgent diarrhoea, pain and fatigue, and associated
stigma, can lead to people becoming depressed, anxious and isolated
(Crohn’s & Colitis UK Quality of Life Survey 2017 and 2018).
Crohn’s care has moved towards delivering personalised care and support,
and not just remission, with a greater focus on the holistic needs of people
with Crohn’s disease (IBD Standards 2019).
We would point out that the current guideline for Crohn’s is not aligned with
the IBD Standards or the most up-to-date British Society of
Gastroenterology IBD guideline.
The technology/
intervention		 AbbVie Yes, however, to clarify risankizumab is administered in induction by
intravenous infusion followed by subcutaneous maintenance injection.
It should also be noted that in addition to marketing authorization for
moderate to severe plaque psoriasis, risankizumab also has marketing
authorization for active psoriatic arthritis in the UK.		 Thank you for your
comment. The scope
has been updated to
clarify the
administration method
and include the
marketing authorisation
for active psoriatic
arthritis.
British Society of
Gastroenterology		 Aminosalicylates should be removed from comparators.
Please remove all technologies related to irritable bowel syndrome (this is
distinct from Crohn’s disease /inflammatory bowel disease and not relevant
whatsoever to this appraisal)
I.e., ‘Irritable bowel syndrome in adults: diagnosis and management’ (2017).
NICE guideline 61; ‘irritable bowel syndrome in adults’ (2016). NICE quality
standard 114.		 Thank you for your
comment. The
comparators are kept
inclusive at this stage.
Stakeholders can
provide justification
around the most
appropriate
comparators and the
committee will consider

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Section Consultee/
Commentator		 Comments [sic] Action
this during the
appraisal. The scope
has been updated to
reflect comments
around associated
guidance.
Population British Society of
Gastroenterology		 The published evidence for RZB from the ADVANCE, MOTIVATE and
FORTIFY Programmes include patients with luminal Crohn’s disease (ileal,
ileocolonic and colonic), and does not include perianal fistulising Crohn’s
Disease. So, the EAMS use should be restricted to luminal Crohn’s disease
only		 Thank you for your
comment. The purpose
of this scope is to set
out the parameters for a
technology evaluation
which is a separate
process to EAMs. The
committee will consider
the clinical evidence
during this evaluation.
However, the
population has been
kept broad at this stage
to accommodate any
potential change in
marketing authorisation.
No changes needed to
the scope.
Comparators AbbVie We note that a comparison to conventional care is not required in the
conventional care failure population.		 Thank you for your
comment. Conventional
care has been removed
as a comparator.

National Institute for Health and Care Excellence

Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
British Society of
Gastroenterology		 There is inadequate head-to-head data to determine at what point in a
treatment pathway risankizumab should be used according to efficacy.
Based on the published evidence, risankizumab should be approved for use
after one or more biologic failure after discussion in a IBD MDT, and with all
medical and surgical options for treatment of Crohn’s disease discussed
with the patient. The drug has not been compared with any other biologic in
a head-to-head trial either for biologic responsive or non-responsive groups
so no conclusions can be derived for its efficacy in these situations.
Network meta-analysis suggests that its efficacy is best after anti TNF
failure.
Many factors are taken into account in current clinical practise when
deciding which of these drugs in the best initial option for a patient
E.g. a New diagnosis >65 yrs. may be directed toward ustekinumab or
vedo due to the preferable side effect profile is this cohort when compared
to anti-TNF
b Patient with perianal fistulating disease will be given infliximab as the
evidence base for its use in this cohort is greatest. As mentioned RZB has
not been investigated in this population.
c. Patient with psoriasis and Crohn’s disease may be preferentially given
ustekinumab as this drug is in both
Flexibility in the pathway is important allowing patient and clinicians to come
to shared decision re optimal care as per BSG guidelines.
Have all relevant comparators for risankizumab been included in the
scope?
Yes
Which treatments are considered to be established clinical practice in
the NHS for Crohn’s disease?
Azathioprine/mercaptopurine		 Thank you for your
comment. Conventional
care has been removed
as a comparator
because it is anticipated
that rizankizumab will
be indicated after at
least 1 previous
therapy. Best
supportive care has
been added as a
comparator for people
who may be taking
risankizumab after all
other biologic treatment
options.

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
Infliximab/adalimumab/vedolizumab/and ustekinumab
Steroids can be used for induction of remission
To prevent post-operative recurrence metronidazole can be used
Siddharth Singh, M Hassan Murad, Mathurin Fumery, Rocio Sedano, Vipul
Jairath, Remo Panaccione, William J Sandborn, Christopher Ma,
Comparative efficacy and safety of biologic therapies for moderate-to-
severe Crohn's disease: a systematic review and network meta-analysis,
The Lancet Gastroenterology & Hepatology,
Volume 6, Issue 12,
2021,
Crohn’s & Coltiis
UK		 We would ask the Committee to remove steroids.
Steroids are not recommended for maintenance of remission and are
associated with a range of side effects (BSG IBD Guideline andIBD
Standards 2019).		 Thank you for your
comment. Conventional
therapy (steroids) has
been removed from the
scope.
Outcomes British Society of
Gastroenterology		 Are the outcomes listed appropriate?
‘The outcome measures listed are
•
disease activity (remission, response, relapse)
•
mucosal healing
•
surgery
•
adverse effects of treatment
health-related quality of life.’
Definitions of remission vary in studies:
Important to include clinical as well as endoscopic remission.
Response should include clinical, biochemical eg CRP and faecal
calprotectin measures		 Thank you for your
comment. The list of
outcomes is not
intended to be
exhaustive at this stage.
Where relevant, the
company is welcomed
to provide the evidence
on all outcomes that are
important for people
with the condition
during the evaluation.

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
Should include steroid free remission as a surrogate marker of relapse.
Crohn’s & Colitis
UK		 We would ask the Committee to consider additions of:
•
Avoidance of steroid therapy
•
Patient experience and outcomes.
•
Improved medicine adherence and self-management.
•
Hospitalisation, readmission and emergency admissions
The ability to treat earlier with a personalised drug treatment regime judged
to be more clinically effective has the potential to reduce the need for
surgery. For women of childbearing age the chance to delay or potentially
prevent surgery, which can reduce fecundity, is desirable.		 Thank you for your
comment. The list of
outcomes is not
intended to be
exhaustive at this stage.
Where relevant, the
company is welcomed
to provide the evidence
on all outcomes that are
important for people
with the condition
during the evaluation.
Equality and
Diversity		 AbbVie None identified. Thank you for your
comment. No action
required.
British Society of
Gastroenterology		 No I do not think the proposed remit and scope exclude any people or
population as described		 Thank you for your
comment. No changes
to the scope needed.
Crohn’s & Colitis
UK		 The mode of administration is a benefit for those with disabilities and
remote communities in terms of reducing the need for travel to hospital and
could potentially improve adherence.		 Thank you for your
comment. No changes
to the scope needed.
Other
considerations		 British Society of
Gastroenterology		 Yes
Consider adding in patients who have not responded to vedolizumab or
have contraindications to this		 Thank you for your
comment. Where
relevant evidence
allows, the committee
will consider whether

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Section Consultee/
Commentator		 Comments [sic] Action
Are there any other subgroups of people in whom risankizumab is
expected to be more clinically effective and cost effective or other
groups that should be examined separately?
Patients with concomitant psoriasis (cost effective)		 further subgroups as
such shall be
considered during the
appraisal. No changes
to the scope needed.
Tillotts Pharma
UK Ltd		 We do not believe consideration should be given to groups not covered by
the terms of the marketing authorisation (as proposed) such as those who
have not previously received a tumour necrosis factor alpha inhibitor		 Thank you for your
comment. The
committee will only
make recommendations
within the marketing
authorisation.
Consideration of
subgroups based on
place in the treatment
pathway has been
removed from the
scope.
Innovation AbbVie In terms of substantial health-related benefits not accounted for in the QALY
calculation, it is expected that endoscopic outcomes and mucosal healing
will not be reflected in the QALY calculation despite being a key treatment
target in Crohn’s disease. This is because whilst risankizumab included
endoscopic outcomes as primary and secondary endpoints in its trials, the
majority of comparators lack RCT data or variability in the definition of
endoscopic outcomes makes it challenging to compare these outcomes
robustly.
Endoscopic and mucosal healing outcomes for risankizumab will be
provided in the submission.		 Thank you for your
comment. No changes
to the scope needed.

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022

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Section Consultee/
Commentator		 Comments [sic] Action
British Society of
Gastroenterology		 Currently approved/available Ustekinumab binds the p40 subunit of IL-12
and- 23, whereas risankizumab selectively blocks the IL-23 p19 subunit and
therefore offers another treatment option to Crohn’s disease patients who
have not responded to other biologics.
There are no head-to-head trials in Crohn’s disease to suggest one is more
effective or safer that the other.
Both already approved for use in psoriasis (TA596 for risankizumab and
TA340 for ustekinumab).		 Thank you for your
comment. No changes
to the scope needed.
Crohn’s & Colitis
UK		 There is also an advantage to a further treatment option that can be
administered at home, which avoids the need for patients to take time off
work or education and during the current pandemic also avoids any
potential risks associated with travel to hospital.		 Thank you for your
comment. No changes
to the scope needed.
Tillotts Pharma
UK Ltd		 Whilst this technology appears to provide a further option for management
of patients with severe disease in whom existing treatments have been
unsuccessful or unsuitable, it does not appear to offer a step change in the
management of Crohn’s disease.		 Thank you for your
comment. No changes
to the scope needed.
Questions for
consultation		 AbbVie Q1) At what point in the treatment pathway would risankizumab be
used? Would it be used as an alternative to:
•
Tumour necrosis factor-alpha inhibitors (infliximab and
adalimumab); or
•
Vedolizumab and ustekinumab
Or would risankizumab be used after these treatments already
available in the NHS?
We would expect risankizumab to be used in line with its marketing
authorisation. We also note that ustekinumab is a treatment option after		 Thank you for your
comment. No changes
to the scope needed.

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Section Consultee/
Commentator		 Comments [sic] Action
conventional care alongside the Tumour necrosis factor-alpha inhibitors
(infliximab and adalimumab) in bullet point one.
Q2) Have all relevant comparators for risankizumab been included in
the scope? Which treatments are considered to be established clinical
practice in the NHS for Crohn’s disease?
Our comments on comparators have been captured above.
Q3) Are the outcomes listed appropriate?
Yes.
Q4) Where do you consider risankizumab will fit into the existing NICE
pathway, Crohn’s disease?
Our comments on the population have been captured above.
Q5) NICE is committed to promoting equality of opportunity,
eliminating unlawful discrimination and fostering good relations
between people with particular protected characteristics and others.
Please let us know if you think that the proposed remit and scope may
need changing in order to meet these aims. In particular, please tell
us if the proposed remit and scope:
•
could exclude from full consideration any people protected by
the equality legislation who fall within the patient population for which
risankizumab will be licensed;
•
could lead to recommendations that have a different impact on
people protected by the equality legislation than on the wider
population, e.g. by making it more difficult in practice for a specific
group to access the technology;
•
could have any adverse impact on people with a particular
disability or disabilities.

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Section Consultee/
Commentator		 Comments [sic] Action
Please tell us what evidence should be obtained to enable the
Committee to identify and consider such impacts.
No issues identified.
Q6) Do you consider that the use of risankizumab can result in any
potential significant and substantial health-related benefits that are
unlikely to be included in the QALY calculation? Please identify the
nature of the data which you understand to be available to enable the
Appraisal Committee to take account of these benefits.
Our response on the health-related benefits excluded from the QALY
calculation are captured above.
Q7) To help NICE prioritise topics for additional adoption support, do
you consider that there will be any barriers to adoption of this
technology into practice? If yes, please describe briefly.
None identified.
Tillotts Pharma
UK Ltd		 Should it be approved for use by NICE based on its safety, clinical and cost
effectiveness, risankizumab, should be limited to the maintenance treatment
of patients with moderate to severe Crohn’s disease who have had an
inadequate response, lost response, or were intolerant to either
conventional therapy or a biologic agent.
According to the information in Appendix B, clinical studies do not include
the use of risankizumab in the induction of remission of active Crohn’s
disease and therefore maintenance therapy appears to be the limit of its
utility.		 Thank you for your
comment. Where
relevant and
appropriate,
risankizumab’s
positioning in the
treatment pathway will
be considered during
the appraisal. The
comparators in the
scope have been
updated to include best

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Section Consultee/
Commentator		 Comments [sic] Action
It would therefore fit into the existing NICE pathway (NG129) after existing
conventional (conventional steroids. budesonide, mercaptopurine,
azathioprine, methotrexate) and biologic (infliximab, adalimumab) agents.
Continued therapy beyond 8 weeks should be carefully reconsidered in a
patient with no improvement within this time period.		 supportive care if
risankizumab is taken
after all biologics
currently in the
treatment pathway.

The following consultees/commentators indicated that they had no comments on the draft remit and/or the draft scope

Janssen

Bladder and Bowel Community (not taking part)

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Risankizumab for previously treated moderately to severely active Crohn’s disease [ID3986] Issue date: April 2022