Tips for searching:
• You have to select a product and type at least 2 words to activate the search
• Use only words that are specific to the information you are looking for
• Avoid typing questions or sentences
Please do not use this field to report adverse events or product complaints. Adverse events and product complaints should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow card in the Google play or Apple app store. Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on 01256 315 000.
Omvoh ® ▼ (mirikizumab)
This information is intended for UK registered healthcare professionals only in response to your search for information. For current information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk
Does Omvoh® (mirikizumab) affect the liver?
In phase 2 and 3 studies that included 4802 patients with 11,003.1 patient years (PY) of exposure to mirikizumab, 349 patients (7.3%) reported a hepatic disorder (incidence rate per 100 PY, 3.3; 95% CI, 3.0-3.7).
Content Overview
Information from the label - liver-associated side effects of mirikizumab
Treatment-Emergent Hepatic Events in the Phase 3 Crohn's Disease Clinical Trial: VIVID-1
Treatment-Emergent Hepatic Enzyme Elevations in VIVID-1
- Additional Information on Hepatic Events in LUCENT-1
- Additional Information on Hepatic Events in LUCENT-2
Treatment-Emergent Hepatic Enzyme Elevations in LUCENT-1 and LUCENT-2
Additional Background Information on Ulcerative Colitis and Hepatic Disorders
Information from the label - liver-associated side effects of mirikizumab
Cases of drug-induced liver injury (including one case meeting Hy’s Law criteria) occurred in patients receiving mirikizumab in clinical trials.1
- Liver enzymes and bilirubin should be evaluated at baseline and monthly during induction (including extended induction period, if applicable).
Thereafter, liver enzymes and bilirubin should be monitored (every 1 ‑ 4 months) according to standard practice for patient management and as clinically indicated.
If increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are observed and drug‑induced liver injury is suspected, mirikizumab must be discontinued until this diagnosis is excluded.1
Mirikizumab has not been studied in patients with hepatic impairment. No dose adjustments are considered necessary. More information can be found in the Omvoh Summary of Product Characteristics in the sections1
- 4.2 Posology and Method of Administration
- 4.4 Special warnings and precautions for use
- 4.8 Undesirable effects
- 5.2 Pharmacokinetic properties
Please find below more information about the liver-related adverse events observed in the pivotal studies. A complete description of these studies is available in section 5.1 in the Summary of Product Characteristics.1
Treatment-Emergent Hepatic Events in the Phase 3 Crohn's Disease Clinical Trial: VIVID-1
During the 52-week VIVID-1 study, at least one hepatic event was reported in
- 6.2% of patients who received mirikizumab
- 2.6% of patients who received ustekinumab, and
- 4.3% patients who received placebo (Frequency of Hepatic Events in the VIVID-1 Clinical Trial,).2
Eventb |
Mirikizumab |
Ustekinumab |
Placebo |
Hepatic event |
39 (6.2) [6.8]c |
8 (2.6) [2.8] |
9 (4.3) [7.8] |
Abbreviations: EAIR = exposure-adjusted incidence rates; PYE = patient years of exposure.
aIncludes all patients who received at least one dose of study drug.
bData presented as n (%) [EAIR].
cThe estimated rate difference (95% CI) was 4 (1.1 to 6.9) for mirikizumab vs ustekinumab and -1 (-6.5 to 4.5) for mirikizumab vs placebo.
Treatment-Emergent Hepatic Enzyme Elevations in VIVID-1
The proportion of patients in each treatment group who presented with hepatic enzyme elevations during the 52-week VIVID-1 study is presented in Summary of Elevated Hepatic Lab Values in the VIVID-1 Clinical Trial,.2
Lab Testb |
Mirikizumab |
Ustekinumab |
Placebo |
ALT |
|||
Increased ≥3× ULN |
12 (1.9) |
6 (2.0) |
0 (0.0) |
Increased ≥5× ULN |
3 (0.5) |
1 (0.3) |
0 (0.0) |
Increased ≥10× ULN |
0 (0.0) |
1 (0.3) |
0 (0.0) |
AST |
|||
Increased ≥3× ULN |
9 (1.4) |
7 (2.3) |
2 (1.0) |
Increased ≥5× ULN |
2 (0.3) |
4 (1.3) |
0 (0.0) |
Increased ≥10× ULN |
0 (0.0) |
2 (0.7) |
0 (0.0) |
ALP |
|||
Increased ≥2× ULN |
7 (1.1) |
0 (0.0) |
2 (1.0) |
ALT or AST ≥3× ULN and TB ≥2× ULN |
1 (0.2)c |
0 (0.0) |
0 (0.0) |
ALP ≥2× ULN and TB ≥2× ULN |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; PYE = patient years of exposure; TB = total bilirubin; ULN = upper limit of normal.
aSafety population representing all patients who received at least one dose of study drug.
bData presented as n (%).
cThe increases in ALT or AST and TB were not concomitant. The patient had a diagnosis of Gilbert’s syndrome with fluctuating indirect hyperbilirubinemia throughout the study and a one-time ALT increase of 3.6× ULN at week 48 when TB was normal.
Treatment-Emergent Hepatic Events in the Phase 3 Ulcerative Colitis Clinical Trials: LUCENT-1, LUCENT-2, and LUCENT-3
During the 12-week induction phase (LUCENT-1), at least one hepatic event was reported in
- 1.6% of patients who received mirikizumab, and
- 1.6% of patients who received placebo.3
In the 40-week maintenance phase (LUCENT-2), at least one hepatic event was reported in
- 3.1% of patients rerandomized to mirikizumab, and
- 2.1% of patients rerandomized to placebo.3
Among patients who received extended induction treatment with mirikizumab, 1.9% reported at least one hepatic event.3
Among patients who received open-label maintenance dosing, 1.8% reported at least one hepatic event.3
Through the first 100 weeks of LUCENT-3 (week 52 to week 152 of continuous mirikizumab treatment), 3.2% of patients reported at least one hepatic event.4
Frequency of Hepatic Events in the LUCENT Clinical Trial Program provides additional information on hepatic events in the clinical trial program.
Eventa |
Treatment Group |
|
LUCENT-1 MIRI Induction |
MIRI 300 mg IV Q4W (n=958) |
PBO IV Q4W (n=321) |
LUCENT-1 Week 12 |
||
Hepatic event |
15b (1.6) |
5 (1.6) |
LUCENT-2 MIRI Induction Responders |
MIRI 200 mg SC Q4W (n=389) |
PBO SC Q4W (n=192) |
LUCENT-2 Week 40 |
||
Hepatic event |
12c (3.1) |
4 (2.1) |
LUCENT-2 MIRI Induction Delayed Responders |
OL Extended Induction |
OL Maintenance of Delayed Responders |
LUCENT-2 Week 12 |
LUCENT-2 Week 40 |
|
Hepatic event |
6 (1.9%) |
3 (1.8) |
LUCENT-3 |
OL Maintenance of MIRI Induction Responders |
|
Week 100d |
||
Hepatic event |
11 (3.2) |
|
Abbreviations: IV = intravenous; MIRI = mirikizumab; OL = open-label; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous.
aData presented as n (%).
bFive of the 15 patients had more than one event, resulting in a total of 20 events.
cThree of the 12 patients had more than one event, resulting in a total of 19 events.
dRepresents 152 weeks of continuous mirikizumab treatment.
Additional Information on Hepatic Events in LUCENT-1
There was no significant difference between placebo and mirikizumab in the frequency of hepatic-related adverse events.5
A total of 20 hepatic-related events occurred in the mirikizumab group. Five of the 15 patients who received mirikizumab had more than one event. As such,
- 3 patients had both mild aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased
- 1 patient had both moderate AST and ALT increased, and
- 1 patient had both mild gamma-glutamyl transferase (GGT) increased and mild hypertransaminasemia.5
Additional Information for Hepatic-Related Events in Patients Who Received Mirikizumab in LUCENT-1 in the Appendix lists additional information on the events.
All of the hepatic-related events in the mirikizumab group were mild except for one moderate case of AST increased and one moderate case of ALT increased in a single patient, and one moderate case of hyperbilirubinemia. None of the events were classified as serious adverse events (Additional Information for Hepatic-Related Events in Patients Who Received Mirikizumab in LUCENT-1 in Appendix).5
No patients temporarily or permanently discontinued mirikizumab due to a hepatic adverse event.5
There were no reports of hepatic failure, hepatic fibrosis, hepatic cirrhosis, or liver-related coagulation and bleeding disturbances.5
Hepatic-Related Adverse Events in the LUCENT-1 Induction Clinical Study shows the numbers of hepatic-related adverse events for each treatment group in LUCENT-1.
Additional Information for Hepatic-Related Events in Patients Who Received Mirikizumab in LUCENT-1 in the Appendix presents additional information on the cases of hepatic-related adverse events in participants who received mirikizumab in the LUCENT-1 study, including event outcome and relationship to study treatment.
Adverse Eventa |
Treatment Group |
|
LUCENT-1 MIRI Induction |
MIRI 300 mg IV Q4W (n=958) |
PBO IV Q4W (n=321) |
LUCENT-1 Week 12 |
||
AST increased |
5 (0.5) |
1 (0.3) |
ALT increased |
4 (0.4) |
1 (0.3) |
GGT increased |
4 (0.4) |
2 (0.6) |
Blood bilirubin increased |
3 (0.3) |
0 (0.0) |
Hepatic function abnormal |
1 (0.1) |
0 (0.0) |
Hyperbilirubinemia |
1 (0.1) |
0 (0.0) |
Hypertransaminasemia |
1 (0.1) |
0 (0.0) |
Liver function test increased |
1 (0.1) |
0 (0.0) |
Hepatic enzyme increased |
0 (0.0) |
1 (0.3) |
Hepatomegaly |
0 (0.0) |
1 (0.3) |
Liver function test abnormal |
0 (0.0) |
1 (0.3) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; IV = intravenous; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks.
aData presented as n (%).
Additional Information on Hepatic Events in LUCENT-2
Mirikizumab Induction Responders
There was no significant difference between placebo and mirikizumab in the frequency of hepatic-related adverse events.5
A total of 19 hepatic-related events occurred in the mirikizumab group. Three of the 12 patients who received mirikizumab had more than one event. As such,
- 1 patient had mild cases of ALT increased, AST increased, GGT increased, and liver function test increased, and moderate blood bilirubin increased
- 1 patient had mild cases of ALT increased, AST increased, and GGT increased, and
- 1 patient had both mild ALT increased and AST increased.5
Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Mirikizumab in LUCENT-2 and Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Placebo in LUCENT-2 in the Appendixlist additional information on the events.
All of the hepatic-related events in the mirikizumab group were mild except for one moderate case each of blood bilirubin increased, GGT increased, hepatic enzyme increased, autoimmune hepatitis, and nonalcoholic fatty liver disease. All of the hepatic-related events in the placebo group were mild except for one patient with moderate ALT increased. None of the hepatic adverse events were classified as serious adverse events (Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Mirikizumab in LUCENT-2 and Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Placebo in LUCENT-2 in Appendix).5
No patients temporarily discontinued mirikizumab due to a hepatic adverse event. One patient with autoimmune hepatitis discontinued from the study, although the investigator did not attribute the event to study treatment (Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Mirikizumab in LUCENT-2 in Appendix).5
Hepatic-Related Adverse Events in the Mirikizumab Induction Responders for the LUCENT-2 Maintenance Clinical Study shows the numbers of hepatic-related adverse events for each treatment group.
Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Mirikizumab in LUCENT-2 and Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Placebo in LUCENT-2 in the Appendix present additional information on the cases of hepatic-related adverse events in mirikizumab induction responders who received mirikizumab or placebo in LUCENT-2, including event outcome and relationship to study treatment.
Adverse Eventa |
Treatment Group |
|
LUCENT-2 MIRI Induction Responders |
MIRI 200 mg SC Q4W (n=389) |
PBO SC Q4W (n=192) |
LUCENT-2 Week 40b |
||
ALT increased |
4 (1.0) |
1 (0.5) |
GGT increased |
4 (1.0) |
1 (0.5) |
AST increased |
3 (0.8) |
0 (0.0) |
Blood bilirubin increased |
2 (0.5) |
0 (0.0) |
Hepatic enzyme increased |
1 (0.3) |
1 (0.5) |
Liver function test increased |
2 (0.5) |
0 (0.0) |
Liver function test abnormal |
0 (0.0) |
1 (0.5) |
Autoimmune hepatitis |
1 (0.3) |
0 (0.0) |
Hepatic steatosis |
1 (0.3) |
1 (0.5) |
Nonalcoholic fatty liver disease |
1 (0.3) |
0 (0.0) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous.
aData presented as n (%).
bRepresenting 52 weeks of continuous treatment.
Clinically Significant Hepatic-Related Adverse Events
Elevated Hepatic Enzymes and Hepatic Steatosis in a Mirikizumab Induction Responder Rerandomized to Placebo
One mirikizumab induction responder who was rerandomized to placebo for LUCENT-2 experienced a mild increase in hepatic enzymes 63 days after their final dose of intravenous mirikizumab and mild hepatic steatosis 132 days into LUCENT-2.5
The patient's liver function tests were within normal limits when entered into LUCENT-2. At the time of the initial event, the patient had laboratory values
- 1.2 times the upper limit of normal (ULN) for ALT
- 3.5 times the ULN for AST
- 1.3 times the ULN for total bilirubin, and
- 12.9 times the ULN for GGT.5
The patient was taking the relevant concomitant medication sulfasalazine and was a concurrent alcohol user. The patient did not interrupt treatment with mirikizumab. At the time of study completion, the increased hepatic enzymes had recovered, and the hepatic steatosis was ongoing. Given the time since the last dose of mirikizumab and ongoing alcohol use, the hepatic enzyme elevations were assessed by the investigator as consistent with alcohol intake.5
This patient is listed in Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Placebo in LUCENT-2 in the Appendix.
Autoimmune Hepatitis in a Mirikizumab Induction Responder Rerandomized to Mirikizumab
A mirikizumab induction responder who was re-randomized to mirikizumab in LUCENT-2 experienced a moderate treatment-emergent adverse event of autoimmune hepatitis on study day 123, approximately 10 days after the last dose of subcutaneous mirikizumab 200 mg.5
The patient's relevant concomitant medications were azathioprine, prednisolone, propofol, remifentanil, and acetaminophen. Azathioprine had been previously discontinued due to suspected hepatotoxicity and prednisolone was being tapered per LUCENT-2 protocol requirements. Azathioprine and prednisolone were reinitiated for the treatment of autoimmune hepatitis and study drug was discontinued.5
The investigator concluded the autoimmune hepatitis was not related to mirikizumab.5
This patient is listed in Additional Information for Hepatic-Related Events in Mirikizumab Induction Responders Who Received Mirikizumab in LUCENT-2 in the Appendix.
Mirikizumab Induction Nonresponders
Open-label Extended Induction
Patients who did not achieve a clinical response to either mirikizumab or placebo during the 12-week induction phase of LUCENT-1 received open-label extended induction treatment with an additional 3 doses of mirikizumab 300 mg infused intravenously every 4 weeks for the first 12 weeks of LUCENT-2.3
Of the 6 patients who experienced a hepatic-related adverse event,
- 1 patient experienced both moderate hepatic enzyme increased and mild cholestatic pruritus, and
- 1 patient experienced moderate GGT increased.3,5
The other adverse events were mild, and none of the adverse events were serious.3,5
Hepatic-Related Adverse Events in the Mirikizumab Induction Nonresponders for the LUCENT-2 Maintenance Clinical Study shows the numbers of hepatic-related adverse events, and Additional Information for Hepatic-Related Events in Mirikizumab Induction Nonresponders in the Appendix lists additional information on the events.
Open-label Maintenance of Delayed Responders
Patients who achieved a clinical response with extended induction therapy compared with LUCENT-1 baseline received open-label maintenance dosing with mirikizumab 200 mg injected subcutaneously every 4 weeks through week 40 of LUCENT-2.3
Hepatic-Related Adverse Events in the Mirikizumab Induction Nonresponders for the LUCENT-2 Maintenance Clinical Study shows the numbers of hepatic-related adverse events, and Additional Information for Hepatic-Related Events in Mirikizumab Induction Nonresponders in the Appendix lists additional information on the events.
Adverse Eventa |
Treatment Group |
|
LUCENT-2 MIRI Induction Nonresponders |
OL Induction MIRI 300 mg IV (n=313) |
OL Maintenance of Delayed Responders |
LUCENT-2 Week 12b |
LUCENT-2 Week 40c |
|
GGT increased |
2 (0.6) |
0 (0.0) |
Transaminases increased |
2 (0.6) |
0 (0.0) |
AST increased |
1 (0.3) |
1 (0.6) |
Hepatic enzyme increased |
1 (0.3) |
0 (0.0) |
Cholestatic pruritus |
1 (0.3) |
0 (0.0) |
Liver function test increased |
0 (0.0) |
1 (0.6) |
Liver disorder |
0 (0.0) |
1 (0.6) |
Abbreviations: AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; IV = intravenous; MIRI = mirikizumab; OL = open-label; SC = subcutaneous.
aData presented as n (%).
bRepresenting 24 weeks of continuous treatment.
cRepresenting 52 weeks of continuous treatment.
Treatment-Emergent Hepatic Enzyme Elevations in LUCENT-1 and LUCENT-2
Liver Function Test Values That Increased in the LUCENT-1 Induction and LUCENT-2 Maintenance Clinical Studies shows the proportions of patients who received mirikizumab in the ulcerative colitis clinical development program that had hepatic enzyme elevations.
Parametera |
LUCENT-1 |
LUCENT-2 |
LUCENT-2 |
|||
Week 12 |
Week 40b |
LUCENT-2 Week 12c |
LUCENT-2 Week 40b |
|||
MIRI 300 mg IV (n=958) |
PBO IV (n=321) |
MIRI 200 mg SC (n=389) |
PBO SC (n=192) |
OL Induction MIRI 300 mg IV (n=313) |
OL Maintenance of Delayed Responders |
|
ALT |
||||||
Increased ≥3x ULN |
4 (0.4) |
2 (0.6) |
3 (0.8) |
1 (0.5) |
3 (1.0) |
2 (1.2) |
Increased ≥5x ULN |
1 (0.1) |
1 (0.3) |
3 (0.8) |
0 (0.0) |
1 (0.3) |
0 (0.0) |
Increased ≥10x ULN |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (0.3) |
0 (0.0) |
AST |
||||||
Increased ≥3x ULN |
4 (0.4) |
0 (0.0) |
4 (1.0) |
1 (0.5) |
2 (0.6) |
2 (1.2) |
Increased ≥5x ULN |
2 (0.2) |
0 (0.0) |
3 (0.8) |
0 (0.0) |
1 (0.3) |
2 (1.2) |
Increased ≥10x ULN |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Bilirubin |
||||||
Increased ≥2x ULN |
6 (0.6) |
1 (0.3) |
2 (0.5) |
4 (2.1) |
1 (0.3) |
0 (0.0) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; IV = intravenous; MIRI = mirikizumab; OL = open-label; PBO = placebo; SC = subcutaneous; ULN = upper limit of normal.
aData presented as n (%).
bRepresenting a total of 52 weeks of continuous therapy.
cRepresenting a total of 24 weeks of continuous therapy.
One patient who received open-label extended induction therapy with mirikizumab in the LUCENT-2 study experienced an increase in ALT and total bilirubin levels meeting Hy's Law criteria. The patient discontinued mirikizumab and the event resolved.3
Additional Background Information on Ulcerative Colitis and Hepatic Disorders
A retrospective case series analysis of 141 patients detected the prevalence of hepatic laboratory test increases among patients with ulcerative colitis as 19.9%, including increases in serum
Common hepatobiliary manifestations of ulcerative colitis include
References
1Omvoh [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands. (GB)
2Ferrante M, D'Haens G, Jairath V, et al; VIVID Study Group. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024;404(10470):2423-2436. https://doi.org/10.1016/S0140-6736(24)01762-8
3D'Haens G, Dubinsky M, Kobayashi T, et al; LUCENT Study Group. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023;388(26):2444-2455. https://doi.org/10.1056/NEJMoa2207940
4Sands BE, D'Haens G, Clemow DB, et al. Three-year efficacy and safety of mirikizumab following 152 weeks of continuous treatment for ulcerative colitis: results from the LUCENT-3 open-label extension study. Inflamm Bowel Dis. Published online October 25, 2024. https://doi.org/10.1093/ibd/izae253
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6Cappello M, Randazzo C, Bravatà I, et al. Liver function test abnormalities in patients with inflammatory bowel diseases: a hospital-based survey. Clin Med Insights Gastroenterol. 2014;7:25-31. https://doi.org.10.4137/CGast.S13125
7Gizard E, Ford AC, Bronowicki JP, Peyrin-Biroulet L. Systematic review: the epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2014;40(1):3-15. https://doi.org/10.1111/apt.12794
8Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol. 2008;14(3):331-337. https://doi.org/10.3748/wjg.14.331
Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Appendix
Patient |
Event |
Severity |
Action Taken With Study Druga |
Event Outcome |
Relationship to Study Treatment |
Discontinuation Due to Event |
1 |
AST increased |
Mild |
Dose not changed |
Not recovered/not resolved |
Yes |
No |
ALT increased |
Mild |
Dose not changed |
Not recovered/not resolved |
Yes |
No |
|
2 |
AST increased |
Mild |
Dose not changed |
Recovering/resolving |
Yes |
No |
ALT increased |
Mild |
Dose not changed |
Recovering/resolving |
Yes |
No |
|
3 |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
Yes |
No |
ALT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
|
4 |
AST increased |
Moderate |
Dose not changed |
Not recovered/not resolved |
No |
No |
ALT increased |
Moderate |
Dose not changed |
Not recovered/not resolved |
No |
No |
|
5 |
GGT increased |
Mild |
Dose not changed |
Not recovered/not resolved |
No |
No |
Hypertransaminasemia |
Mild |
Dose not changed |
Not recovered/not resolved |
Nob |
No |
|
6 |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
7 |
GGT increasedc |
Mild |
Dose not changed |
Not recovered/not resolved |
Nod |
No |
8 |
GGT increased |
Mild |
Dose not changed |
Not recovered/not resolved |
Yes |
No |
9 |
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
10 |
Blood bilirubin increased |
Mild |
Dose not changed |
Not recovered/not resolved |
No |
No |
11 |
Blood bilirubin increased |
Mild |
Dose not changed |
Recovering/resolving |
No |
No |
12 |
Blood bilirubin increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
13 |
Hepatic function abnormal |
Mild |
NA |
Not recovered/not resolved |
No |
No |
14 |
Hyperbilirubinemia |
Moderate |
Dose not changed |
Not recovered/not resolved |
Yese |
No |
15 |
Liver function test increased |
Mild |
Dose not changed |
Recovered/resolved |
Yes |
No |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; NA = not applicable.
aAction taken with study treatment could be dose reduced, dose increased, dose not changed, drug interrupted, drug withdrawn, not applicable, or unknown.
bThe investigator believed the event may be related to non-study treatment.
cCompared with baseline visit.
dThe investigator believed the event may be related to another medical condition.
eThe investigator believed the event may be related to the study disease.
Patient |
Event |
Severity |
Action Taken With Study Druga |
Event Outcome |
Relationship to Study Treatment |
Discontinuation Due to Event |
1 |
ALT increased |
Mild |
Dose not changed |
Recovered/resolved |
Yesb |
No |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
Yesb |
No |
|
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
Yesb |
No |
|
2 |
ALT increased |
Mild |
Dose not changed |
Recovered/resolved |
Nob |
No |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
Nob |
No |
|
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
Nob |
No |
|
Liver function test increased |
Mild |
Dose not changed |
Not recovered/not resolved |
Nob |
No |
|
Blood bilirubin increased |
Moderate |
Dose not changed |
Recovered/resolved |
No |
No |
|
3 |
ALT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
|
4 |
ALT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
5 |
GGT increased |
Moderate |
Dose not changed |
Recovering/resolving |
No |
No |
6 |
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
7 |
Blood bilirubin increased |
Mild |
Dose not changed |
Recovered/resolved |
Yes |
No |
8 |
Hepatic enzyme increased |
Moderate |
Dose not changed |
Recovered/resolved |
Noc |
No |
9 |
Liver function test increased |
Mild |
Dose not changed |
Not recovered/not resolved |
No |
No |
10 |
Autoimmune hepatitis |
Moderate |
Drug withdrawn |
Not recovered/not resolved |
No |
Yes |
11 |
Hepatic steatosis |
Mild |
Dose not changed |
Not recovered/not resolved |
No |
No |
12 |
Nonalcoholic fatty liver disease |
Moderate |
Dose not changed |
Not recovered/not resolved |
Nob |
No |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GABA = gamma-aminobutyric acid; GGT = gamma-glutamyl transferase.
aAction taken with study treatment could be dose reduced, dose increased, dose not changed, drug interrupted, drug withdrawn, not applicable, or unknown.
bThe investigator believed the event may be related to another medical condition.
cThe investigator believed the event was related to gamma-aminobutyric acid (GABA) supplement.
Patient |
Event |
Severity |
Action Taken With Study Druga |
Event Outcome |
Relationship to Study Treatment |
Discontinuation Due to Event |
1 |
Hepatic enzyme increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
Hepatic steatosis |
Mild |
Dose not changed |
Recovering/resolving |
No |
No |
|
2 |
ALT increased |
Moderate |
Dose not changed |
Recovered/resolved |
No |
No |
3 |
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
4 |
Liver function test abnormal |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
Abbreviations: ALT = alanine aminotransferase; GGT = gamma-glutamyl transferase.
aAction taken with study treatment could be dose reduced, dose increased, dose not changed, drug interrupted, drug withdrawn, not applicable, or unknown.
Patient |
Event |
Severity |
Action Taken With Study Druga |
Event Outcome |
Relationship to Study Treatment |
Discontinuation Due to Event |
Treatment period: open-label extended induction |
||||||
1 |
GGT increased |
Moderate |
Dose not changed |
Recovered/resolved |
Nob |
No |
2 |
GGT increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
3 |
Transaminases increased |
Mild |
Dose not changed |
Not recovered/not resolved |
Yes |
No |
4 |
Transaminases increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
5 |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
6 |
Cholestatic pruritus |
Mild |
Dose not changed |
Recovered/resolved |
No |
No |
Hepatic enzyme increased |
Moderate |
Drug withdrawn |
Recovered/resolved |
Yes |
Yes |
|
Treatment period: open-label maintenance of delayed responders |
||||||
7 |
Liver function test increased |
Mild |
Dose not changed |
Recovered/resolved |
Yes |
No |
8 |
Liver disorder |
Mild |
Dose not changed |
Not recovered/not resolved |
No |
No |
9 |
AST increased |
Mild |
Dose not changed |
Recovered/resolved |
Noc |
No |
Abbreviations: AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase.
aAction taken with study treatment could be dose reduced, dose increased, dose not changed, drug interrupted, drug withdrawn, not applicable, or unknown.
bThe investigator believed the event may be related to study disease.
cThe investigator believed the event may be related to study procedure.
Date of Last Review: 15 January 2025