STELARA®
(ustekinumab)
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STELARA® (ustekinumab)
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Occurrence of Abnormal Liver Function Tests in Adult Patients Treated with STELARA
Last Updated: 01/02/2025
SUMMARY
- Summarized in this response are relevant data on abnormal liver function tests (LFTs) from the pivotal phase 3 clinical trial programs and open-label long-term extensions (LTEs) in adult patients with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC), active psoriatic arthritis (PsA), and moderate to severe psoriasis (PsO) treated with STELARA.1
- 8 - Additional data are available through a randomized clinical trial, a prospective study, and several retrospective studies, which are summarized below.9
-12
CLINICAL DATA IN CROHN’S DISEASE AND ULCERATIVE COLITIS
The safety and efficacy of STELARA in adults with moderately to severely active CD were evaluated in the pivotal, phase 3, randomized, double-blind, placebo-controlled, multicenter clinical program (UNITI & IM-UNITI). The program consisted of 2 induction studies and 1 maintenance study.13
Additionally, the safety and efficacy of STELARA in adult patients with moderately to severely active UC was evaluated in the pivotal, phase 3, randomized, double-blind, placebo-controlled, multicenter clinical program (UNIFI). The program consisted of 1 induction study and 1 maintenance study.14
For the occurrence of abnormal LFTs in adult patients with CD or UC through 52 weeks of therapy and through the open-label LTE, see Tables: Number of Pooled CD and UC Patients with 1 or More Treatment-Emergent Adverse Events on Induction and Maintenance Therapy (Up to 52 Weeks Total) by MedDRA System-Organ Class and Preferred Term; Treated Patients Who Were Randomized in CD or UC Phase 3 Maintenance Studies and Number of Pooled CD and UC Patients with 1 or More Treatment-Emergent Adverse Events from Week 44 through the Final Safety Visit by MedDRA System-Organ Class and Preferred Term; Treated Patients Who Entered the LTE.
| Inflammatory Bowel Disease (CD and UC Pooled) | ||||
|---|---|---|---|---|
| Placebo SC Maintenanceb | STELARA 90 mg SC q12wc | STELARA 90 mg SC q8wc | STELARA Combined (q8w and q12w)c | |
| Patients treated, N | 308 | 304 | 307 | 611 |
| Average duration of follow-up, weeks | 47.27 | 49.00 | 48.60 | 48.80 |
| Investigations, n (%) | ||||
| Increased ALT | 4 (1.3) | 6 (2.0) | 10 (3.3) | 16 (2.6) |
| Increased AST | 4 (1.3) | 5 (1.6) | 8 (2.6) | 13 (2.1) |
| Increased blood ALP | 1 (0.3) | 1 (0.3) | 2 (0.3) | 2 (0.3) |
| Increased blood bilirubin | 0 | 1 (0.3) | 0 | 1 (0.2) |
| Increased LFT | 3 (1.0) | 0 | 2 (0.7) | 2 (0.3) |
| Abnormal LFT | 2 (0.6) | 0 | 2 (0.7) | 2 (0.3) |
| Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CD, Crohn’s disease; LFT, liver function test; MedDRA, Medical Dictionary for Regulatory Activities; q12w, every 12 weeks; q8w, every 8 weeks; SC, subcutaneous; UC, ulcerative colitis. aUp to 60 weeks for patients who entered maintenance at week 16 of the induction study in UC CNTO1275UCO3001. bPatients who were in clinical response to STELARA intravenous induction dosing and were randomized to placebo SC on entry into the maintenance study. cIncludes data up to the time of meeting loss of response criteria for patients who had a dose adjustment in CD. | ||||
| Crohn’s Disease | ||||
|---|---|---|---|---|
| Placebo SCa | STELARA 90 mg SC q12wb | STELARA 90 mg SC q8wc | STELARA Combined (q8w and q12w) | |
| Patients who entered the LTE, N | 151 | 213 | 354 | 567 |
| Average duration of follow-up, weeks | 60.8 | 164.7 | 163.0 | 163.6 |
| Investigations, n (%) | ||||
| Increased ALT | 1 (0.7) | 0 | 6 (1.7) | 6 (1.1) |
| Increased AST | 0 | 0 | 6 (1.7) | 6 (1.1) |
| Increased blood ALP | 0 | 1 (0.5) | 1 (0.3) | 2 (0.4) |
| Increased blood bilirubin | 0 | 2 (0.9) | 0 | 2 (0.4) |
| Increased LFT | 0 | 0 | 2 (0.6) | 2 (0.4) |
| Increased liver enzyme | 0 | 0 | 1 (0.3) | 1 (0.2) |
| Abnormal liver enzyme | 0 | 0 | 1 (0.3) | 1 (0.2) |
| Ulcerative Colitis | ||||
| Placebo SC Maintenanced | STELARA 90 mg SC q12we | STELARA 90 mg SC q8wf | STELARA Combined (q8w and q12w) | |
| Patients who entered the LTE, N | 188 | 141 | 380 | 457 |
| Average duration of follow-up, weeks | 44.1 | 105.1 | 137.5 | 146.8 |
| Investigations, n | ||||
| Increased ALT | 0 | 3 | 18 | 20 |
| Increased AST | 0 | 1 | 16 | 16 |
| Increased blood ALP | 0 | 1 | 2 | 3 |
| Increased liver enzyme | 0 | 0 | 4 | 4 |
| Transaminases increased | 0 | 0 | 1 | 1 |
| Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CD, Crohn’s disease; IV, intravenous; LFT, liver function test; LTE, long-term extension; MedDRA, Medical Dictionary for Regulatory Activities; q12w, every 12 weeks; q8w, every 8 weeks; SC, subcutaneous; UC, ulcerative colitis. aIncludes patients who were in clinical response to STELARA IV induction dosing, were randomized and received placebo SC on entry into this maintenance study, and did not meet loss of response criteria from week 8 through week 32; and includes patients who were in clinical response to placebo IV induction dosing and received placebo SC on entry into this maintenance study. bIncludes patients who were in clinical response to STELARA IV induction dosing, were randomized and received STELARA 90 mg SC q12w, and did not meet loss of response criteria from week 8 through week 32; and includes patients who were not in clinical response to placebo IV induction dosing, received STELARA 130 mg IV at week 0, achieved clinical response at week 8, and initiated STELARA 90 mg SC q12w. cIncludes patients who were in clinical response to STELARA IV induction dosing, were randomized on entry into this maintenance study, received STELARA 90 mg SC q8w, or met loss of response criteria from week 8 through week 32 and received STELARA 90 mg SC q8w thereafter; and includes patients who were not in clinical response to STELARA IV induction dosing, received STELARA 90 mg SC at week 0, achieved clinical response at week 8, and initiated STELARA 90 mg SC q8w. dIncludes data from week 44 through the final safety visit, or up to the dose adjustment if patients had a dose adjustment during the LTE, for patients who were in clinical response to STELARA IV induction dosing and were randomized to placebo SC on entry into the maintenance study; and includes data from week 44 through the final safety visit for patients who were in clinical response to placebo IV induction dosing and received placebo SC on entry into the maintenance study. eIncludes data from week 44 through the final safety visit, or up to the dose adjustment if patients had a dose adjustment during the LTE for patients who were in clinical response to STELARA IV induction dosing and were randomized to STELARA 90 mg SC q12w on entry into the maintenance study. fIncludes patients who were in clinical response to STELARA IV induction dosing and were randomized to receive STELARA 90 mg SC q8w on entry into the maintenance study, with data from week 44 through the final safety visit and includes patients who were in clinical response to STELARA IV induction dosing, randomized to receive placebo SC or STELARA 90 mg SC q12w on entry into the maintenance study, and had a dose adjustment to STELARA 90 mg SC q8w, with data from the time of dose adjustment through the final safety visit and includes patients who were not in clinical response to STELARA at induction week 8 but were in clinical response at induction week 16 after SC administration of STELARA at induction week 8 and received STELARA 90 mg SC q8w on entry into the maintenance study with data from week 44 through the final safety visit. | ||||
CLINICAL DATA IN Psoriatic arthritis
The efficacy and safety of STELARA in adult patients with active PsA was assessed through 2 phase 3, randomized, multicenter, placebo-controlled clinical studies (PSUMMIT I and PSUMMIT II) through week 24.15
For the occurrence of abnormal LFTs in adult patients with PsA through 52 weeks of therapy and through the open-label LTE see Tables: Number of Patients with 1 or More Treatment-Emergent Adverse Events through the End of the Reporting Period by MedDRA System-Organ Class and Preferred Term; Patients Treated in PsA Phase 3 Studies
| Placebo→STELARA 45 mga | STELARA 45 mgb | STELARA 90 mgb | STELARA Combined | |
|---|---|---|---|---|
| Patients treated, N | 269 | 308 | 308 | 885 |
| Average duration of follow-up, weeks | 32.00 | 51.65 | 51.17 | 45.51 |
| Investigations, n (%) | ||||
| Increased ALT | 5 (1.9) | 5 (1.6) | 10 (3.2) | 20 (2.3) |
| Increased AST | 3 (1.1) | 4 (1.3) | 5 (1.6) | 12 (1.4) |
| Increased blood ALP | 0 | 0 | 1 (0.3) | 1 (0.1) |
| Increased liver enzyme | 0 | 1 (0.3) | 2 (0.6) | 3 (0.3) |
| Abnormal liver enzyme | 0 | 1 (0.3) | 0 | 1 (0.1) |
| Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities; PsA, psoriatic arthritis. aPatients who early escaped at week 16 or crossed over at week 24. bIncludes all treated patients irrespective of early escape. | ||||
| Placebo→STELARA 45 mga | STELARA 45 mgb | STELARA 90 mgc | STELARA Combined | |
|---|---|---|---|---|
| Patients treated, N | 189 | 205 | 204 | 598 |
| Average duration of follow-up, weeks | 79.93 | 96.82 | 98.01 | 91.89 |
| Investigations, n (%) | ||||
| Increased ALT | 3 (1.6) | 7 (3.4) | 9 (4.4) | 19 (3.2) |
| Increased AST | 2 (1.1) | 4 (2.0) | 3 (1.5) | 9 (1.5) |
| Increased liver enzyme | 0 | 1 (0.5) | 2 (1.0) | 3 (0.5) |
| Abnormal liver enzyme | 0 | 1 (0.5) | 0 | 1 (0.2) |
| LFT abnormal | 3 (1.6) | 8 (3.9) | 4 (2.0) | 15 (2.5) |
| Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; LFT, liver function test; MedDRA, Medical Dictionary for Regulatory Activities. aIncludes patients who early escaped at week 16 or crossed over at week 24. bIncludes patients who did not early escape at week 16 and patients who early escaped at week 16. cIncludes all treated patients irrespective of early escape. | ||||
CLINICAL DATA IN PSORIASIS
The efficacy and safety of STELARA in adult patients with PsO was assessed through 2 phase 3, randomized, multicenter, placebo-controlled clinical studies (PHOENIX 1 and PHOENIX 2).17
For the occurrence of abnormal LFTs in adult patients with PsO through week 52 of PHOENIX 1 and PHOENIX 2, see Table: Number of Patients with 1 or More Treatment-Emergent Adverse Events through Week 52 by MedDRA System-Organ Class and Preferred Term.
Number of Patients with 1 or More Treatment-Emergent Adverse Events through Week 52 by MedDRA System-Organ Class and Preferred Term7
| Placebo (0-12 weeks) | STELARA 45 mg | STELARA 90 mg | STELARA Combineda | |
|---|---|---|---|---|
| Patients treated, N | 255 | 255 | 255 | 753 |
| Average duration of follow-up, weeks | 12.5 | 52.9 | 52.9 | 49.7 |
| Investigations, n (%) | ||||
| Increased ALT | 1 (0.4) | 4 (1.6) | 7 (2.7) | 14 (1.9) |
| Increased AST | 1 (0.4) | 3 (1.2) | 5 (2.0) | 9 (1.2) |
| Increased blood bilirubin | 0 | 2 (0.8) | 1 (0.4) | 3 (0.4) |
| Increased liver enzyme | 1 (0.4) | 2 (0.8) | 0 | 3 (0.4) |
| Abnormal LFT | 0 | 2 (0.8) | 0 | 2 (0.3) |
| PHOENIX 2 | ||||
| Placebo (0-12 weeks) | STELARA 45 mg | STELARA 90 mg | STELARA Combineda | |
| Patients treated, N | 410 | 409 | 411 | 1212 |
| Average duration of follow-up, weeks | 12.3 | 49.9 | 50.3 | 46.5 |
| Investigations, n | ||||
| Increased ALT | 0 | 3 (0.7) | 5 (1.2) | 10 (0.8) |
| Increased AST | 0 | 0 | 3 (0.7) | 4 (0.3) |
| Increased blood bilirubin | 0 | 1 (0.2) | 0 | 1 (0.1) |
| Increased liver enzyme | 1 (0.2) | 2 (0.5) | 1 (0.2) | 4 (0.3) |
| Abnormal LFT | 0 | 2 (0.5) | 0 | 2 (0.2) |
| Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; LFT, liver function test; MedDRA, Medical Dictionary for Regulatory Activities. aIncludes patients who were receiving placebo→STELARA 45 mg, placebo→STELARA 90 mg, STELARA 45 mg, and STELARA 90 mg. | ||||
For the occurrence of abnormal LFTs in adult patients with PsO through the LTE for PHOENIX 1 and 2, see Table: Number of Patients with 1 or More Treatment-Emergent Adverse Events through the Final Safety Visit by MedDRA System-Organ Class and Preferred Term in PHOENIX 1 and PHOENIX 2.
| STELARA 45 mga | STELARA 90 mga | STELARA Combined | |
|---|---|---|---|
| Patients treated, N | 984 | 1184 | 1965 |
| Average duration of follow-up, weeks | 184.5 | 204.2 | 215.4 |
| Investigations, n (%) | |||
| Increased ALT | 24 (2.4) | 30 (2.5) | 54 (2.7) |
| Increased AST | 8 (0.8) | 16 (1.4) | 24 (1.2) |
| Increased blood ALP | 3 (0.3) | 3 (0.3) | 6 (0.3) |
| Increased blood bilirubin | 3 (0.3) | 1 (0.1) | 4 (0.2) |
| Increased liver enzyme | 11 (1.1) | 6 (0.5) | 17 (0.9) |
| Abnormal LFT | 5 (0.5) | 4 (0.3) | 9 (0.5) |
| Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities. aPlacebo crossover patients were included in STELARA columns after crossover to STELARA. For PHOENIX 2, patients who were dose escalated from 45 mg to 90 mg are switched to the corresponding column following dose escalation. | |||
Additional clinical data
Additional data are available through several clinical trials, a prospective study and several retrospective studies. Please see Table: Summary of Additional Clinical Data Reporting the Occurrence of Abnormal LFTs in Patients Receiving STELARA.
| Primary Author and Year | Study Design | Patient Population | STELARA Dosing Regimen | Investigation |
|---|---|---|---|---|
| Psoriasis | ||||
| Igarashi et al (2012)9 | Ph 2/3 double-blind, PBO-controlled, multicenter, 72-week study | 160 adult patients with PsO | 45 or 90 mg SC at weeks 0 and 4 and q12w thereafter, or PBO at weeks 0 and 4a | Increased ALT occurred in: Weeks 0-72b STELARA 45 mg: 6/79 STELARA 90 mg: 9/75 |
| Youn et al (2021)10 | Prospective, observational, multicenter, ~52-week study | 977 adult patients with PsO | 45 mg SC ≤100 kg, 90 mg SC >100 kg | LFT abnormality occurred in 10 patients (1.2 per 100 PYs) |
| Llamas-Velasco et al (2015)11 | Retrospective, observational 52-week study | 44 adult patients with PsO | 45 mg SC at weeks 0 and 4 and q12w thereafter | Grade 1 elevation (up to 3x ULN) of liver transaminases occurred in 6 patients; no severe elevations were observed. Neither of the 2 patients with elevated liver transaminases at baseline developed problems during treatment with STELARA. |
| Wilder et al (2014)12 | Retrospective, 52-week analysis | 119 adult patients with PsO | 45 mg SC <100 kg; 90 mg SC >100 kg at weeks 0, 4 and 16. Additional doses ranged from 45-90 mg q8w-q12w per clinical response | Elevated liver enzymes were the most common laboratory abnormality (n=52 [44%]). Of these patients, 28 were receiving concomitant MTX whereas 12 patients received MTX prior to STELARA therapy. Abnormalities were mild and did not require discontinuation of STELARA. |
| Abbreviations: ALT, alanine aminotransferase; LFT, liver function test; MTX, methotrexate; PBO, placebo; ph, phase; PsO, psoriasis; PY, patient-years; q12w, every 12 weeks; q8w, every 8 weeks; SC, subcutaneous; ULN, upper limit of normal. aPBO patients crossed over to STELARA 45 or 90 mg at week 12 and treatment at weeks 16, 28, 40 and 52. bPatients who experienced adverse events while receiving placebo are included in weeks 0-72 results based on their randomization group (PBO to 45 mg or PBO to 90 mg). PBO-treated patients who never received STELARA (n=4) were excluded from the week 0-72 analyses. | ||||
Literature Search
A literature search of MEDLINE®
References
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