How often does inflammatory bowel disease occur with TALTZ® (ixekizumab) treatment for psoriasis, psoriatic arthritis, and axial spondyloarthritis?

Inflammatory Bowel Disease Summary

Cases of new or exacerbations of CD and UC have been reported. Overall, these events are uncommon (<1%). Caution should be exercised when prescribing ixekizumab to patients with IBD, including CD and UC, and patients should be monitored closely.¹ 

Patients treated with ixekizumab may be at increased risk of IBD. In clinical trials, CD and UC, including exacerbations, occurred at a greater frequency in the ixekizumab group than the placebo control group.²

During ixekizumab treatment, monitor for onset or exacerbation of IBD and if IBD occurs, discontinue ixekizumab and initiate appropriate medical management.²

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

The frequency is

• 0.5% with an EAIR of 0.2 per 100 PYs for the adult psoriasis program as of the 5-year safety exposure (N=5898)

• 0.2% with an EAIR of 0.1 per 100 PYs for the PsA program as of the 3-year safety exposure (N=1401), and

• 1.4% with an EAIR of 1.0 per 100 PYs for the axSpA program with more than 1-year safety exposure (N=929).³

Crohn's Disease and Ulcerative Colitis Events

Psoriasis Clinical Trials

Per external adjudication, 29 patients with psoriasis had reported IBD adjudicated as UC (n=17, IR=0.098 per 100 PY), and CD (n=12, IR=0.069 per 100 PY) across 13 psoriasis trials as of March 2019 (Table 1) (N=5898 adult patients with plaque psoriasis representing 17,331 PY of exposure).³ Of the 29 patients with IBD events, 6 patients with CD discontinued the trial and 10 patients with UC discontinued the trial at the discretion of the investigator.¹

Table 1. Summary of Adjudicated^a Inflammatory Bowel Disease Events in Adult Psoriasis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Cutoff March 2019)^1,3,4

	Induction Periodb		Maintenance Periodc			13 Adult PsO Trials
	Placebo N=791	Ixekizumab N=2328		Placebod N=402	Ixekizumab  N=824		All Ixekizumab Exposures  N=5898
Total PY	180	534.5		188.2	627.6		17,331.1
Inflammatory Bowel Disease, n (%)	0	3 (0.13)		3 (0.75)	4 (0.49)		29 (0.5)
IR/100 PY	0	0.56		1.59	0.64		0.167
Crohn's Disease, n (%)	0	1 (0.04)		3 (0.75)	1 (0.12)		12 (0.2)
IR/100 PY	0	0.19		1.59	0.16		0.069
Ulcerative colitis, n (%)	0	2 (0.09)		0	3 (0.36)		17 (0.28)
IR/100 PY	0	0.37		0	0.48		0.098

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.

^a Data 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.

^b UNCOVER-1, -2, and -3 (week 0-12).

^c UNCOVER-1 and -2 (week 12-60).

^d Patients received ixekizumab during the induction period.

A summary of the adjudicated events with self-reported history of IBD from this data set is provided in Table 2. The number of patients who self-reported a history of IBD was 31. Of the 31 patients with self-reported history of IBD, 28 patients reported no events of IBD during the trials.¹

Table 2. New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab from 13 Adult Psoriasis Trials as of March 2019¹

	All Ixekizumab Psoriasis Exposures  N=5898
Total Exposure as of March 2019, PY	17,331.1
Patients with a self-reported history of IBD, n (%)	31 (0.5)a
Total inflammatory bowel disease, n (%) [IR/100 PY]	29 (0.5) [0.167]
Crohn's disease, n (%) [IR/100 PY]	12 (0.2) [0.069]
Patients with ≥1 event and a self-reported history of IBD, n	0
Patients with ≥1 event and no known history of IBD, n	12
Ulcerative colitis, n (%) [IR/100 PY]	17 (0.28) [0.098]
Patients with ≥1 event and a self-reported history of IBD, n	3
Patients with ≥1 event and no known history of IBD, n	14

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.

^a 28 of the 31 patients with self-reported history of IBD reported no events of IBD during the trials.

Psoriatic Arthritis Clinical Trials

Per external adjudication, 3 patients with PsA had reported cases of IBD which were adjudicated as UC (n=1, IR=0.045 per 100 PY) and CD (n=2, IR=0.090 per 100 PY) across 4 PsA trials as of March 2019 (Table 3) (N=1401 patients with PsA representing 2228.6 PY of exposure).³ Of the 3 patients with IBD events, 1 patient discontinued the trial at the discretion of the investigator.¹

Table 3. Summary of Adjudicated^a Inflammatory Bowel Disease Events in Psoriatic Arthritis Clinical Trials: Frequency and Exposure-Adjusted Incidence Rates (All Ixekizumab Cutoff March 2019)^1,3,5

	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	2228.6
Inflammatory Bowel Disease, n (%)	0	0c	3 (0.2)
IR/100 PY	0	0	0.135
Crohn's disease, n (%)	0	0	2 (0.1)
IR/100 PY	0	0	0.090
Ulcerative colitis, n (%)	0	0	1 (0.1)
IR/100 PY	0	0	0.045

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.

^a Data 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.

^b Data are from first 24 weeks of SPIRIT-P1 and SPIRIT-P2 trials.

^c One 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.

A summary of the adjudicated events with self-reported history of IBD from this data set is provided in Table 4. The number of patients with self-reported history was 14. Of the 14 patients with self-reported history of IBD, 14 patients reported no events of IBD during the trials.¹

Table 4. New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 PsA Trials as of March 2019¹

	All Ixekizumab PsA Exposures N=1401 n (%)
Total Exposure as of March 2019, PY	2228.6
Patients with a self-reported history of IBD, n (%)	14 (1.0)a
Total inflammatory bowel disease, n (%) [IR/100 PY]	3 (0.2) [0.135]b
Crohn’s Disease, n (%) [IR/100 PY]	2 (0.1) [0.090]
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) [0.045]
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.

^a 14 of the 14 patients with self-reported history of IBD reported no events of IBD during the trials.

^b One 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.

Axial Spondyloarthritis Trials

Per external adjudication, 13 patients had reported IBD adjudicated as UC (n=6, IR=0.449 per 100 PY), and CD (n=7, IR=0.524 per 100 PY) across 4 axSpA trials as of April 2019 (Table 5) (N=929 patients with axSpA representing 1336.2 PY of exposure)³. Of the 13 patients with IBD events, 5 patients discontinued the trial at the discretion of the investigator.¹

Table 5. Summary of Adjudicated^a Inflammatory Bowel Disease Events in Axial Spondyloarthritis Trials as of April 2019¹

	Placebo Through 16 Weeks N=294b	Ixekizumab Through 16 Weeks N=574c	All Ixekizumab Exposures Across 4 axSpA Trials N=929
Total PY	89.9	175.8	1336.2
Inflammatory bowel disease, n (%)	1 (0.3)d,e	5 (0.9)	13 (1.4)
IR/100 PY	1.1	2.8	0.973
Crohn's disease, n (%)	1 (0.3)f	4 (0.7)	7 (0.8)
IR/100 PY	1.1	2.3	0.524
Ulcerative colitis, n (%)	0	1 (0.2)	6 (0.6)
IR/100 PY	0g	0.6	0.449

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.

^a Data 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.

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

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

^d 1 patient from COAST-W was reported as UC and later adjudicated as CD.

^e There was 1 patient from COAST-X with history of UC and reported as UC but adjudicated as “insufficient information."

^f 1 patient from COAST-W was reported as UC and later adjudicated as CD.

^g There was 1 patient from COAST-X with history of UC and reported as UC but adjudicated as “insufficient information."

A summary of the adjudicated events with self-reported history of IBD from this data set is provided in Table 6. The number of patients with a self-reported history was 33. Of the 33 patients with self-reported history of IBD, 29 patients reported no events of IBD during the trials.¹

Table 6. New Onset and Exacerbation of Crohn’s Disease and Ulcerative Colitis in Patients Treated With Ixekizumab From 4 axSpA Trials (as of April 2019)^a1

Total exposure, PY	1336.2
Patients with a self-reported history of IBD, n (%)	33 (3.6)b
Total inflammatory bowel disease, n (%) [IR/100 PY]	13 (1.4) [0.973]
Crohn's disease, n (%) [IR/100 PY]	7 (0.8) [0.524]
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]	6 (0.6) [0.449]
Patients with ≥1 event and a self-reported history of IBD, n	3
Patients with ≥1 event and no known history of IBD, n	3

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.

^a One patient who received placebo in COAST-W had IBD adjudicated as Crohn's disease. In addition, 1 patient in COAST-X who received placebo reported ulcerative colitis but this event was adjudicated as insufficient information and the patient had a history of ulcerative colitis.

^b 29 of the 33 patients with self-reported history of IBD reported no events of IBD during the trials.

Enclosed Prescribing Information

TALTZ® (ixekizumab) injection, for subcutaneous administration, Lilly

References

The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).

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

2. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.

3. Genovese MC, Mysler E, Tomita T, et al. Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatology (Oxford). Published online May 25, 2020. https://doi.org/10.1093/rheumatology/keaa189

4. Reich 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

5. Genovese MC, Colombel JF, Gellett AM, et al. Incidence of inflammatory bowel disease among patients treated with ixekizumab: an update on adjudicated data from an integrated database of patients with psoriasis and psoriatic arthritis. Presented at: American College of Rheumatology/AHRP 2018 Annual Scientific Meeting; October 19-24, 2018; Chicago, IL.

Glossary

AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis

axSpA = axial spondyloarthritis

CD = Crohn's disease

EAIR = exposure adjusted incidence rate

IBD = inflammatory bowel disease

nr-axSpA = nonradiographic axial spondyloarthritis

PY = patient-years

UC = ulcerative colitis