Taltz ® (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Can Taltz® (ixekizumab) be used in Patients with Comorbid Inflammatory Bowel Disease?

Ixekizumab is not recommended in patients with inflammatory bowel disease (IBD). We provide clinical trial data on IBD adverse events, including Crohn’s disease and ulcerative colitis.

UK_cFAQ_IXE335_INFLAMMATORY_BOWEL_DISEASE_PsO_PsA_axSpA
UK_cFAQ_IXE335_INFLAMMATORY_BOWEL_DISEASE_PsO_PsA_axSpA
en-GB

Summary

Prescribers should be aware of and follow the appropriate language in local labeling for ixekizumab regarding inflammatory bowel disease (IBD).

Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab. Ixekizumab is not recommended in patients with inflammatory bowel disease.1

If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated.1

There is no contraindication for the use of ixekizumab in patients with a history of IBD.2

In the ixekizumab phase 3 clinical trial program across psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), the overall IBD frequency is reported as uncommon (<1%) for the placebo-controlled periods.

The exposure adjusted incidence rate (EAIR) as of March 2021 is

  • 0.2 per 100 patient-years (PY) for the adult psoriasis program as of the 5-year exposure data set (N=6892)
  • 0.1 per 100 PY for the PsA program as of the 3-year exposure data set (N=1401), and
  • 0.8 per 100 PY for the axSpA program as of the 3-year exposure data set (N=932).3-5

Crohn's Disease and Ulcerative Colitis Events in the Clinical Trials

Psoriasis

Per external adjudication, 31 adult patients with psoriasis had reported cases of IBD which were adjudicated as UC (n=18, IR=0.1 per 100 PY) and CD (n=13, IR=0.1 per 100 PY) across 17 adult psoriasis trials (N=6892 patients with 18,025.7 PY of exposure) as of March 2021 (Summary of Adjudicated Inflammatory Bowel Disease Events in Adult Psoriasis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Exposures as of March 2021)). Of the 31 patients with IBD events, 20 discontinued ixekizumab treatment at the discretion of the investigator.2,3

Summary of Adjudicateda Inflammatory Bowel Disease Events in Adult Psoriasis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Exposures as of March 2021)2,3,6

 

Induction Periodb

Maintenance Periodc

17 Adult PsO Trials


Placebo
(N=791)

Ixekizumab
(N=2328)

Placebod
(N=402)

Ixekizumab 
(N=824)

All Ixekizumab Exposures 
(N=6892)

Total PY

180

534.5

188.2

627.6

18,025.7

Inflammatory bowel disease, n (%)

0

3 (0.13)

3 (0.75)

4 (0.49)

31 (0.4)d

IR/100 PY

0

0.56

1.59

0.64

0.2

Crohn's disease, n (%) 

0

1 (0.04)

3 (0.75)

1 (0.12)

13 (0.2)

 IR/100 PY

0

0.19

1.59

0.16

0.1

Ulcerative colitis, n (%)

0

2 (0.09)

0

3 (0.36)

18 (0.3)

 IR/100 PY

0

0.37

0

0.48

0.1

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; PsO = psoriasis; PY = patient-years.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PYs, and then multiplied by 100.

aData on suspected IBD, as identified by events possibly indicative of ulcerative colitis and Crohn’s disease, were collected and the events were adjudicated by an external Clinical Evaluation Committee with expertise in IBD.

bUNCOVER-1, -2, and -3 (week 0-12).

cUNCOVER-1 and -2 (week 12-60).

dTwenty-six cases were listed as treatment-emergent adverse events of IBD. Five additional cases were listed as adverse events of IBD, and these occurred when patients were not on ixekizumab (either occurring when patients were on placebo during the randomized withdrawal period of UNCOVER-2 [n=2], or during follow-up [1 patient each from UNCOVER-2, UNCOVER-3, and IXORA-R]).

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab from 17 Adult Psoriasis Trials as of March 2021 summarizes adjudicated IBD events based on self-reported history of IBD from the March 2021 data set. Across the 17 adult psoriasis trials, the number of patients who self-reported a history of IBD was 35. Of the 35 patients with self-reported history of IBD, 31 patients reported no events of IBD during the trials.2

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab from 17 Adult Psoriasis Trials as of March 20212,3

 

All Ixekizumab Psoriasis Exposures 
(N=6892)

Total Exposure as of March 2021, PY

18,025.7

Patients with a self-reported history of IBD, n (%) 

35 (0.5)a

Total inflammatory bowel disease, n (%) [IR/100 PY]

31 (0.4) [0.2]b

Crohn's disease, n (%) [IR/100 PY]

13 (0.2) [0.1]

Patients with ≥1 event and a self-reported history of IBD, n

1

Patients with ≥1 event and no known history of IBD, n

12

Ulcerative colitis, n (%) [IR/100 PY]

18 (0.3) [0.1]

Patients with ≥1 event and a self-reported history of IBD, n

3

Patients with ≥1 event and no known history of IBD, n

15

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; PY = patient-years.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PYs, and then multiplied by 100.

a31 of the 35 patients with self-reported history of IBD reported no events of IBD during the trials.

bTwenty-six cases were listed as treatment-emergent adverse events of IBD. Five additional cases were listed as adverse events of IBD, and these occurred when patients were not on ixekizumab (either occurring when patients were on placebo during the randomized withdrawal period of UNCOVER-2 [n=2], or during follow-up [1 patient each from UNCOVER-2, UNCOVER-3, and IXORA-R]).

Psoriatic Arthritis

Per external adjudication, 3 patients with PsA had reported cases of IBD which were adjudicated as UC (n=1, IR=0.0 per 100 PY) and CD (n=2, IR=0.1 per 100 PY) across 4 PsA trials (N=1401 patients with 2248 PY of exposure) as of March 2021 (Summary of Adjudicated Inflammatory Bowel Disease Events in Psoriatic Arthritis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Exposures as of March 2021)) . Of the 3 patients with IBD events, 1 discontinued ixekizumab treatment at the discretion of the investigator.4,5

Summary of Adjudicateda Inflammatory Bowel Disease Events in Psoriatic Arthritis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Exposures as of March 2021)2,4,5

 

Placebo Through 24 Weeksb
(N=224)

Ixekizumab Through 24 Weeksb
(N=454)

All Ixekizumab Exposures Across 4 Psoriatic Arthritis Trials 
(N=1401)

Total PY

85.7

193.8

2248

Inflammatory bowel disease, n (%)

0

0c

3 (0.2)d,e

IR/100 PY

0

0

0.1

Crohn's disease, n (%)

0

0

2 (0.1)

IR/100 PY

0

0

0.1

Ulcerative colitis, n (%)

0

0

1 (0.1)

IR/100 PY

0

0

0.0

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; PY = patient-years.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PYs, and then multiplied by 100.

aData on suspected IBD, as identified by events possibly indicative of ulcerative colitis and Crohn’s disease, were collected and the events were adjudicated by an external Clinical Evaluation Committee with expertise in IBD.

bData are from first 24 weeks of SPIRIT-P1 and SPIRIT-P2 trials.

cOne patient had an anal abscess and anal fistula. This event was considered consistent with IBD, but was not adjudicated as Crohn's disease or ulcerative colitis due to insufficient information.

dOne additional patient had an anal abscess and anal fistula. This event was considered consistent with IBD, but was not adjudicated as Crohn's disease or ulcerative colitis due to insufficient information.

eThree patients had events of IBD confirmed by adjudication. One patient had more than 1 event.

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 PsA Trials as of March 2021 summarizes adjudicated IBD events based on self-reported history of IBD from the March 2021 data set. The number of patients with self-reported history was 14 across the 4 PsA trials. None of the 14 patients with self-reported history of IBD reported an IBD event during the trials.2

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 PsA Trials as of March 20212,4,5

All Ixekizumab PsA Exposures
(N=1401)

Total exposure as of March 2021, PY

2248

Patients with a self-reported history of IBD, n (%)

14 (1.0)a

Total inflammatory bowel disease, n (%) [IR/100 PY]

3 (0.2) [0.1]b,c

Crohn’s disease, n (%) [IR/100 PY]

2 (0.1) [0.1]

 Patients with ≥1 event and a self-reported history of IBD, n

0

 Patients with ≥1 event and no known history of IBD, n

2

Ulcerative colitis, n (%) [IR/100 PY]

1 (0.1) [0.0]

Patients with ≥1 event and a self-reported history of IBD, n

0

Patients with ≥1 event and no known history of IBD, n

1

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; PY = patient-years.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PYs, and then multiplied by 100.

aNone of the 14 patients with self-reported history of IBD reported an IBD event during the trials.

bOne additional patient had an anal abscess and anal fistula. This event was considered consistent with IBD, but was not adjudicated as Crohn's disease or ulcerative colitis due to insufficient information.

cThree patients had events of IBD confirmed by adjudication. One patient had more than 1 event.

Axial Spondyloarthritis

Per external adjudication, 17 patients had reported cases of IBD which were adjudicated as UC (n=10, IR=0.5 per 100 PY) and CD (n=7, IR=0.3 per 100 PY) across 4 axSpA trials (N=932 patients with 2096.2 PY of exposure) as of March 2021 (Summary of Adjudicated Inflammatory Bowel Disease Events in Axial Spondyloarthritis Trials as of March 2021). Of the 17 patients with IBD events, 9 discontinued ixekizumab treatment at the discretion of the investigator.2,4

Summary of Adjudicateda Inflammatory Bowel Disease Events in Axial Spondyloarthritis Trials as of March 20212,4

Placebo Through 16 Weeksb
(N=294)
Ixekizumab Through 16 Weeksb 
(N=574)
All Ixekizumab Exposures Across 4 axSpA Trials
(N=932)

Total PY

89.9

175.8

2096.2

Inflammatory bowel disease, n (%)

1 (0.3)c,d

5 (0.9)

17 (1.8)e

IR/100 PY

1.1

2.8

0.8

Crohn's disease, n (%)

1 (0.3)f

4 (0.7)

7 (0.8)

IR/100 PY

1.1

2.3

0.3

Ulcerative colitis, n (%)

0

1 (0.2)

10 (1.1)

IR/100 PY

0e

0.6

0.5

Abbreviations: AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis; axSpA = axial spondyloarthritis; CD = Crohn's disease; IBD = inflammatory bowel disease; IR = incidence rate; nr-axSpA = nonradiographic axial spondyloarthritis; PY = patient-years; UC = ulcerative colitis.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PYs, and then multiplied by 100.

aData on suspected IBD, as identified by events possibly indicative of UC and CD, were collected and the events were adjudicated by an external Clinical Evaluation Committee with expertise in IBD.

bData are from first 16 weeks of COAST-V, COAST-W (AS/r-axSpA), and COAST-X (nr-axSpA) trials.

cOne patient from COAST-W was reported as a case of UC and later adjudicated as a case of CD.

dThere was 1 patient from COAST-X with a history of UC and reported as a case of UC but adjudicated as “insufficient information."

eOne additional event occurred during safety follow-up in the COAST Program and is not counted as a TEAE.

fOne patient from COAST-W was reported as a case of UC and later adjudicated as CD.

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 axSpA Trials (as of March 2021), summarizes adjudicated IBD events based on self-reported history of IBD from the March 2021 data set. The number of patients with a self-reported history was 30. Of the 30 patients with self-reported history of IBD, 25 patients reported no events of IBD during the trials.2

New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 axSpA Trials (as of March 2021)a,2


All Ixekizumab axSpA Exposures
(N=932)

Total exposure as of March 2021, PY

2096.2

Patients with a self-reported history of IBD, n (%)

30 (3.2)b

Total inflammatory bowel disease, n (%) [IR/100 PY]

17(1.8) [0.8]a

Crohn's disease, n (%) [IR/100 PY]

7 (0.8) [0.3]

Patients with ≥1 event and a self-reported history of IBD, n

1

Patients with ≥1 event and no known history of IBD, n

6

Ulcerative colitis, n (%) [IR/100 PY]

10 (1.1) [0.5]

Patients with ≥1 event and a self-reported history of IBD, n

4

Patients with ≥1 event and no known history of IBD, n

6

Abbreviations: axSpA = axial spondyloarthritis; IBD = inflammatory bowel disease; IR = incidence rate; PY = patient-years; TEAE = treatment-emergent adverse event.
Note: Incidence rate was calculated as the total of “definite” and “probable” cases, divided by total PY, and then multiplied by 100.

aOne patient who received placebo in COAST-W reported ulcerative colitis, and was later adjudicated as Crohn's disease. In addition, 1 patient in COAST-X who received placebo had a history of ulcerative colitis and was reported as a case of ulcerative colitis, but was adjudicated as insufficient information.

bTwenty-five of the 30 patients with self-reported history of IBD reported no events of IBD during the trials.

References

1Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Griffiths CEM, Gooderham M, Colombel JF, et al. Safety of ixekizumab in adult patients with moderate-to-severe psoriasis: data from 17 clinical trials with over 18,000 patient-years of exposure. Dermatol Ther (Heidelb). 2022;12:1431-1446. https://doi.org/10.1007/s13555-022-00743-9

4Schwartzman S, Deodhar A, Combe B, et al. Safety profile of ixekizumab for the treatment of psoriatic arthritis and axial spondyloarthritis up to 3 years: an updated integrated safety analysis. Poster presented at: Annual Meeting of the America College of Rheumatology (ACR Convergence Virtual); November 1-10, 2021.

5Deodhar AA, Combe B, Accioly AP, et al. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022;81(7):944-950. https://doi.org/10.1136/annrheumdis-2021-222027

6Reich K, Leonardi C, Langley RG, et al. Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: a presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J Am Acad Dermatol 2017;76(3);441-448.e2. https://dx.doi.org/10.1016/j.jaad.2016.10.027

Date of Last Review: 24 February 2022


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