Korea Post-marketing Surveillance for Xeljanz (Registered) in Ulcerative Colitis Patients

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04071405

Enrollment

110

Registered

2019-08-28

Start date

2020-05-12

Completion date

2022-09-26

Last updated

2024-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis, Autoimmune Diseases, Immune System Diseases, Tofacitinib, Molecular Mechanisms of Pharmacological Action, Jak inhibitor, safety

Brief summary

As required for new medications approved by the Ministry of Food and Drug Safety, safety and efficacy information should be provided for a minimum of 90 patients treated in the setting of routine practice during 4 years following approval (until 19 September 2022). Out of all the enrolled patients, at least 18 cases (20%) will be followed up until the 52nd week to see the long term safety of Xeljanz.

Detailed description

This is an open-label, non-comparative, non-interventional, prospective, and multi-center study conducted in Korean health care centers by accredited physicians (ie, investigators). The study population will be adult patients with moderately to severely active UC who have had an inadequate response or intolerance to the basic treatments or biological agents. Clinical Severity of Ulcerative Colitis is classified as mild, moderate, or severe based on the Mayo score or partial Mayo score. Xeljanz will be administered according to the Dosage and Administration of the approved labeling. There is no visit or activity mandated by this study. The investigator will collect patient data and record the information on each patient's case report form (CRF).

Interventions

OTHERNon-intervention

Non-intervention observational study

Study design

Observational model

CASE_ONLY

Time perspective

OTHER

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Adult ulcerative colitis patients with moderately to severely active disease who has received at least 1 dose of Xeljanz according to the local labeling

Exclusion criteria

* Patients meeting any of the following criteria as per local labeling will not be included in the study. 1. Patients with a history of hypersensitivity to any ingredients of this product. 2. Patients with serious infection (sepsis, etc.) or active infection including localized infection. 3. Patients with active tuberculosis. 4. Patients with severe hepatic function disorder. 5. Patients with an absolute neutrophil count (ANC) \<1,000 cells/mm3. 6. Patients with a lymphocyte count \<500 cells/mm3. 7. Patients with a hemoglobin level \<9 g/dL. 8. Pregnant or possibly pregnant women. 9. Because of lactose contained in this drug, it should not be administered to patients with hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events by Their Other Causality Assessment in Long Term Users	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant when administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events by their other causality assessment (in case of unlikely) were classified as: Disease under the study, Other diseases, Concomitant treatment medication or non-medication, and Other. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure included only long term users. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Their Outcomes	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. AE outcomes were categorized as: recovered; recovered with sequelae; recovering; not recovered; unknown. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events by Their Outcomes in Long Term Users	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. AE outcomes were categorized as: recovered; recovered with sequelae; recovering; not recovered; unknown. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Their Seriousness	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events were classified as per their seriousness as following: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect, other important medical event. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events by Their Seriousness in Long Term Users	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events were classified as per their seriousness as following: results in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent or significant disability/incapacity, results in congenital anomaly/birth defect, other important medical event. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Action Taken	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Action taken with regard to the medicinal product included: permanently discontinued; temporarily discontinued or delayed; dose reduced; dose increased; no change; and not applicable. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events by Action Taken in Long Term Users	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Action taken with regard to the medicinal product included: permanently discontinued; temporarily discontinued or delayed; dose reduced; dose increased; no change; and not applicable. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Their Causality Assessment	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant when administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Causal relationship of AEs to the medicinal product was allocated by the investigator according to the following criteria: certain, probable/likely, possible, unlikely, conditional/unclassified, unassessible/unclassifiable, not applicable. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events by Their Causality Assessment in Long Term Users	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant when administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Causal relationship of AEs to the medicinal product was allocated by the investigator according to the following criteria: certain, probable/likely, possible, unlikely, conditional/unclassified, unassessible/unclassifiable, not applicable. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Their Other Causality Assessment	From first dose of Xeljanz until 52 weeks	An AE was any untoward medical occurrence in a participant when administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events by their other causality assessment (in case of unlikely) were classified as: Disease under the study, Other diseases, Concomitant treatment medication or non-medication, and Other. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Percentage of Participants With Adverse Events, Adverse Drug Reactions, Serious Adverse Events and Serious Adverse Drug Reactions	From first dose of Xeljanz until 52 weeks	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product which need not necessarily have causal relationship with product treatment or usage. Serious adverse event was any adverse event that resulted in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Adverse drug reaction (ADR) was any untoward medical occurrence attributed to Xeljanz. Serious ADR: any ADR resulting in any of following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. 95% confidence interval (CI) was based on Clopper-Pearson method. This outcome measure is reported for all participants including long term users (i.e. treated with Xeljanz for at least 52 weeks).
Number of Participants With Adverse Events, Adverse Drug Reactions, Serious Adverse Events and Serious Adverse Drug Reactions in Long Term Users	From first dose of Xeljanz until 52 weeks	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product which need not necessarily have causal relationship with product treatment or usage. A serious adverse event was any adverse event that resulted in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. An adverse drug reaction (ADR) was any untoward medical occurrence attributed to Xeljanz. Serious ADR: any ADR resulting in any of following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. This outcome measure was analyzed only in long term users.
Percentage of Participants With Unexpected Adverse Events (AE), Unexpected Adverse Drug Reactions, Unexpected Serious Adverse Events (SAE), and Unexpected Serious Adverse Drug Reactions	From first dose of Xeljanz until 52 weeks	Unexpected AE: any event that may be symptomatically, pathophysiologically related to event listed in labeling, but differed from labeled event because of greater severity or specificity. ADR: any untoward medical occurrence attributed to Xeljanz. All events that were not included in Precautions for use section of local product document were classified as unexpected adverse drug reactions. Serious ADR: any ADR resulting in any of following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. SAE: any untoward medical occurrence in participant administered medicinal/nutritional product at any dose that resulted in death was life-threatening. 95% CI was based on Clopper-Pearson method. This outcome measure is reported for all participants including long term users.
Number of Participants With Unexpected Adverse Events, Unexpected Adverse Drug Reactions, Unexpected Serious Adverse Events, and Unexpected Serious Adverse Drug Reactions in Long Term Users	From first dose of Xeljanz until 52 weeks	Unexpected AE: any event that may be symptomatically, pathophysiologically related to event listed in labeling, but differed from labeled event because of greater severity or specificity. ADR: any untoward medical occurrence attributed to Xeljanz. All events that were not included in Precautions for use section of local product document were classified as unexpected adverse drug reactions. Serious ADR: any ADR resulting in any of following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. SAE: any untoward medical occurrence in participant administered medicinal/nutritional product at any dose that resulted in death was life-threatening. This outcome measure was analyzed only in long term users.
Percentage of Participants With Adverse Events of Special Interest	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events of special interest were defined as serious or non-serious AEs which were of scientific and medical concern specific to the investigational product. 95% CI was based on Clopper-Pearson method. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events of Special Interest in Long Term Users	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. Adverse events of special interest were defined as serious or non-serious AEs which were of scientific and medical concern specific to the investigational product. This outcome measure was analyzed only in long term users.
Number of Participants With Adverse Events by Their Severity	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. AEs were categorized as per the severity: mild: did not cause any significant problem to the participant, administration of medicinal product continued without dose adjustment; moderate: caused a problem that did not interfere significantly with usual activities or the clinical status, dose of the medicinal product was adjusted or other therapy was added due to the AE; severe: caused a problem that interfered significantly with usual activities, or the clinical status and the medicinal product was stopped due to AE. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure is reported for all participants including long term users.
Number of Participants With Adverse Events by Their Severity in Long Term Users	From first dose of Xeljanz until 52 weeks	An adverse event was any untoward medical occurrence in a participant administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. AEs were categorized as per the severity: mild: did not cause any significant problem to the participant, administration of medicinal product continued without dose adjustment; moderate: caused a problem that did not interfere significantly with usual activities or the clinical status, dose of the medicinal product was adjusted or other therapy was added due to the AE; severe: caused a problem that interfered significantly with usual activities, or the clinical status and the medicinal product was stopped due to AE. One participant may experience more than one event; hence, one participant may be included in more than one category specified below. This outcome measure was analyzed only in long term users.

Secondary

Measure	Time frame	Description
Mayo Index, Mayo Score and Partial Mayo Score at Week 8, Week 16, Week 24 and Week 52 for Long Term Users	Baseline, Week 8, Week 16, Week 24 and Week 52	Mayo score (MS): measured disease activity (DA) of UC; total score range=0 to 12, higher score=severe DA. Mayo index was based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding, Endoscopy finding, Physician's global assessment (PGA). Each sub-score range=0 to 3,higher score=more severe DA. Stool frequency:0=normal number of stool, 1=1 to 2 stool/day \>normal, 2=3 to 4 stool/day \>normal, 3= \>4 stool/day \>normal; Rectal bleeding:0=None,1=Visible blood with stool less than half time, 2=Visible blood with stool\>half time, 3=Mostly blood with rare stool; Endoscopic finding:0=Normal/inactive, 1=Mild with erythema, decreased vascular pattern, mild friability, 2=Moderate with marked erythema, absent vascular pattern, friability, erosion, 3=Severe with spontaneous bleeding, ulceration, pseudopolyp; PGA: 0=Normal/inactive, 1=Mild, 2=Moderate, 3=severe. Partial MS=sum of all evaluation criteria, except endoscopy finding.Partial MS score range=0 to 9; higher score=more severe DA.
Number of Participants With Mucosal Healing at Week 8, Week 16 and Week 24	Week 8, Week 16 and Week 24	Mucosal healing was defined by Mayo or partial Mayo endoscopic score of 0 or 1 where 0=Normal/inactive disease,1=Mild disease with erythema, decreased vascular pattern, mild friability.
Number of Participants With Mucosal Healing at Week 8, Week 16, Week 24 and Week 52 for Long Term Users	Week 8, Week 16, Week 24 and Week 52	Mucosal healing was defined by Mayo or partial Mayo endoscopic score of 0 or 1 where 0=Normal/inactive disease,1=Mild disease with erythema, decreased vascular pattern, mild friability.
Number of Participants With Remission at Week 8, Week 16 and Week 24	Week 8, Week 16, and Week 24	Clinical remission was defined as Mayo score being less than or equal to 2 or partial MS \<=1 and other sub-scores not more than 1. Total MS score range=0-12, where higher score=severe DA. MS based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding (RB), Finding of endoscopy, PGA. Each sub score range=0 to 3,higher score=more severe DA. Partial MS= sum of all evaluation criteria, except endoscopy finding. Partial MS total score=0 to 9 where, higher score=more severe disease activity.
Number of Participants With Remission at Week 8, Week 16, Week 24 and Week 52 for Long Term Users	Week 8, Week 16, Week 24 and Week 52	Clinical remission was defined as Mayo score being less than or equal to 2 or partial MS \<=1 and other sub-scores not more than 1. Total MS score range=0-12, where higher score=severe DA. MS based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding (RB), Finding of endoscopy, PGA. Each sub score range=0 to 3,higher score=more severe DA. Partial MS= sum of all evaluation criteria, except endoscopy finding. Partial MS total score=0 to 9 where, higher score=more severe disease activity.
Number of Participants With Clinical Response at Week 8, Week 16 and Week 24	Week 8, Week 16 and Week 24	Clinical response was defined as Mayo score being greater than or equal to 3 point, 30% from baseline, decrease of 1 or more in Rectal bleeding score or rectal bleeding score of 0 or 1. Total MS score range=0-12, where higher score=severe DA. MS based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding (RB), Finding of endoscopy, PGA. Each sub score range=0 to 3,higher score=more severe DA. Partial MS= sum of all evaluation criteria, except endoscopy finding. Partial MS total score=0 to 9 where, higher score=more severe disease activity.
Number of Participants With Clinical Response at Week 8, Week 16, Week 24 and Week 52 for Long Term Users	Week 8, Week 16, Week 24 and Week 52	Clinical response was defined as Mayo score being greater than or equal to 3 point, 30% from baseline, decrease of 1 or more in Rectal bleeding score or rectal bleeding score of 0 or 1. Total MS score range=0-12, where higher score=severe DA. MS based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding (RB), Finding of endoscopy, PGA. Each sub score range=0 to 3,higher score=more severe DA. Partial MS= sum of all evaluation criteria, except endoscopy finding. Partial MS total score=0 to 9 where, higher score=more severe disease activity.
Number of Participants According to Final Effectiveness Evaluation by Investigator	From first dose of Xeljanz until 24 weeks	The final effectiveness evaluation was determined by the investigator into 4 categories ('Improved', 'Unchanged', 'Aggravated', 'Not assessible'). Improved: Symptoms of ulcerative colitis have improved or showed adequate maintenance effect after taking Xeljanz; Unchanged: Symptoms have not changed much since taking Xeljanz; Aggravated: Symptoms have worsened after taking Xeljanz; Not assessible.
Mayo Index, Mayo Score and Partial Mayo Score at Baseline, Week 8, Week 16 and Week 24	Baseline, Week 8, Week 16 and Week 24	Mayo score (MS): measured disease activity (DA) of UC; total score range=0 to 12, higher score=severe DA. Mayo index was based on 4 clinical evaluation criteria: Stool frequency, Rectal bleeding, Endoscopy finding, Physician's global assessment(PGA).Each sub-score range=0 to 3,higher score=more severe DA.Stool frequency:0=normal number of stool, 1=1 to 2 stool/day \>normal, 2=3 to 4 stool/day \>normal, 3= \>4 stool/day \>normal; Rectal bleeding:0=None,1=Visible blood with stool less than half time, 2=Visible blood with stool\>half time, 3=Mostly blood with rare stool; Endoscopic finding:0=Normal/inactive, 1=Mild with erythema, decreased vascular pattern, mild friability, 2=Moderate with marked erythema, absent vascular pattern, friability, erosion, 3=Severe with spontaneous bleeding, ulceration, pseudopolyp; PGA: 0=Normal/inactive, 1=Mild, 2=Moderate, 3=severe Partial MS=sum of all evaluation criteria, except endoscopy finding.Partial MS score range=0 to 9;higher score=more severe DA.

Countries

South Korea

Participant flow

Recruitment details

Adult participants with moderately to severely active ulcerative colitis (UC) who had an inadequate response or intolerance to basic treatments or biological agents and were prescribed Xeljanz (tofacitinib) for the first time as part of routine practice at Korean healthcare centers were observed in this post-marketing surveillance study.

Participants by arm

Arm	Count
Tofacitinib Participants with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to basic treatments or biological agents and received tofacitinib as part of routine practice at Korean health care centers were observed.	107
Total	107

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Protocol Violation	3

Baseline characteristics

Characteristic	Tofacitinib	—
Age, Continuous	40.83 Years STANDARD_DEVIATION 13.37	—
Race and Ethnicity Not Collected	—	— Participants
Sex: Female, Male Female	31 Participants	—
Sex: Female, Male Male	76 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 107
other Total, other adverse events	41 / 107
serious Total, serious adverse events	8 / 107

Outcome results

Primary

Number of Participants With Adverse Events, Adverse Drug Reactions, Serious Adverse Events and Serious Adverse Drug Reactions in Long Term Users

An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product which need not necessarily have causal relationship with product treatment or usage. A serious adverse event was any adverse event that resulted in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. An adverse drug reaction (ADR) was any untoward medical occurrence attributed to Xeljanz. Serious ADR: any ADR resulting in any of following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. This outcome measure was analyzed only in long term users.