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

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.