Trial Outcomes & Findings for Long-Term Safety Study Of Tofacitinib In Patients With Juvenile Idiopathic Arthritis (NCT NCT01500551)

A total of 302 eligible participants who had previously completed any of the 3 qualifying/index Juvenile Idiopathic Arthritis (JIA) clinical studies of tofacitinib (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) were enrolled in the current extension study A3921145 (NCT01500551).

Long-Term Safety Study Of Tofacitinib In Patients With Juvenile Idiopathic Arthritis

Parameters: Hematology (hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes, prothrombin international normalized ratio, erythrocyte sedimentation rate), clinical chemistry (bilirubin, direct/indirect bilirubin, aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, cholesterol, high and low density lipoprotein cholesterol, Friedewald estimation, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, C reactive protein), urinalysis (specific gravity, potential of hydrogen (pH), glucose/ protein/ hemoglobin/ erythrocytes/ leukocytes, ketones, leukocyte esterase, hyaline casts, bacteria). Number of participants with at least 1 laboratory abnormality are reported.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily had a causal relationship with the treatment or usage. A serious AE (SAE) was defined as any untoward medical occurrence at any dose that met one or more of the following criteria: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. An TEAE was any AE that occurred following the start of study treatment in this study or increased in severity following the start of study treatment in this study. AE included both SAEs and all non-SAEs.

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Pubertal development was measured using Tanner stage, by age group (2 to \<6 years, 6 to \<12 years, and 12 years or older) for males and females separately. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (fully developed breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes continue to enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size).

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 12. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 24. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 36. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 48. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 60. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 72. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 84. Only rows with non-zero values were reported in this outcome measure.

Physician global evaluation of disease activity assessed overall arthritis appearance at specified time points. The evaluation was based on the participant's disease signs, functional capacity and physical examination. The investigator rated the overall level of disease activity by entering a number from 0 (no disease activity) to 10 (maximum disease activity) on a visual analogue scale (VAS). Higher scores signified more disease activity.

Physician global evaluation of disease activity assessed overall arthritis appearance at specified time points. The evaluation was based on the participant's disease signs, functional capacity and physical examination. The investigator rated the overall level of disease activity by entering a number from 0 (no disease activity) to 10 (maximum disease activity) on a VAS. Higher scores signified more disease activity.

Physician global evaluation of disease activity assessed overall arthritis appearance at specified time points. The evaluation was based on the participant's disease signs, functional capacity and physical examination. The investigator rated the overall level of disease activity by entering a number from 0 (no disease activity) to 10 (maximum disease activity) on a VAS. Higher scores signified more disease activity. In this outcome measure pJIA stands for polyarticular course juvenile idiopathic arthritis.

Physician global evaluation of disease activity assessed overall arthritis appearance at specified time points. The evaluation was based on the participant's disease signs, functional capacity and physical examination. The investigator rated the overall level of disease activity by entering a number from 0 (no disease activity) to 10 (maximum disease activity) on a VAS. Higher scores signified more disease activity.

Physician global evaluation of disease activity assessed overall arthritis appearance at specified time points. The evaluation was based on the participant's disease signs, functional capacity and physical examination. The investigator rated the overall level of disease activity by entering a number from 0 (no disease activity) to 10 (maximum disease activity) on a VAS. Higher scores signified more disease activity.

Active arthritis was defined as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by either pain on motion, or tenderness not due to deformity.

Active arthritis was defined as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by either pain on motion, or tenderness not due to deformity.

Active arthritis was defined as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by either pain on motion, or tenderness not due to deformity.

Active arthritis was defined as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by either pain on motion, or tenderness not due to deformity.

Active arthritis was defined as a joint with swelling or, in the absence of swelling, limitation of motion accompanied by either pain on motion, or tenderness not due to deformity.

CRP was a laboratory measurement test for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

CRP was a laboratory measurement test for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

CRP was a laboratory measurement test for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

CRP was a laboratory measurement test for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

CRP was a laboratory measurement test for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

ESR was a laboratory test that provides a measure of inflammation. A higher rate is consistent with inflammation.

ESR was a laboratory test that provides a measure of inflammation. A higher rate is consistent with inflammation.

ESR was a laboratory test that provides a measure of inflammation. A higher rate is consistent with inflammation.

ESR was a laboratory test that provides a measure of inflammation. A higher rate is consistent with inflammation.

ESR was a laboratory test that provides a measure of inflammation. A higher rate is consistent with inflammation.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. Disability index assessed function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed among a total of 30 items. Each question was rated from Grade 0 to 3, 0= without any difficulty, 1= with some difficulty, 2= with much difficulty, 3= unable to do. If aids or devices were used or assistance was required, the minimum score for that functional area was 2. Parent/legal guardians were required to answer all questions. The disability index was calculated as the mean of the 8 functional areas and scores were averaged to calculate CHAQ disability index, which ranged from 0= no/minimal physical dysfunction to 3= very severe physical dysfunction; higher score indicated more disability.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. Disability index assessed function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed among a total of 30 items. Each question was rated from Grade 0 to 3, 0= without any difficulty, 1= with some difficulty, 2= with much difficulty, 3= unable to do. If aids or devices were used or assistance was required, the minimum score for that functional area was 2. Parent/legal guardians were required to answer all questions. The disability index was calculated as the mean of the 8 functional areas and scores were averaged to calculate CHAQ disability index, which ranged from 0= no/minimal physical dysfunction to 3= very severe physical dysfunction; higher score indicated more disability.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. Disability index assessed function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed among a total of 30 items. Each question was rated from Grade 0 to 3, 0= without any difficulty, 1= with some difficulty, 2= with much difficulty, 3= unable to do. If aids or devices were used or assistance was required, the minimum score for that functional area was 2. Parent/legal guardians were required to answer all questions. The disability index was calculated as the mean of the 8 functional areas and scores were averaged to calculate CHAQ disability index, which ranged from 0= no/minimal physical dysfunction to 3= very severe physical dysfunction; higher score indicated more disability.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. Disability index assessed function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed among a total of 30 items. Each question was rated from Grade 0 to 3, 0= without any difficulty, 1= with some difficulty, 2= with much difficulty, 3= unable to do. If aids or devices were used or assistance was required, the minimum score for that functional area was 2. Parent/legal guardians were required to answer all questions. The disability index was calculated as the mean of the 8 functional areas and scores were averaged to calculate CHAQ disability index, which ranged from 0= no/minimal physical dysfunction to 3= very severe physical dysfunction; higher score indicated more disability.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. Disability index assessed function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed among a total of 30 items. Each question was rated from Grade 0 to 3, 0= without any difficulty, 1= with some difficulty, 2= with much difficulty, 3= unable to do. If aids or devices were used or assistance was required, the minimum score for that functional area was 2. Parent/legal guardians were required to answer all questions. The disability index was calculated as the mean of the 8 functional areas and scores were averaged to calculate CHAQ disability index, which ranged from 0= no/minimal physical dysfunction to 3= very severe physical dysfunction; higher score indicated more disability.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. For the assessment of discomfort index, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall arthritis pain of participant from 0 (no pain) to 10 (very severe pain), on a VAS, where higher scores indicated more severe pain.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. For the assessment of discomfort index, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall arthritis pain of participant from 0 (no pain) to 10 (very severe pain), on a VAS, where higher scores indicated more severe pain.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. For the assessment of discomfort index, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall arthritis pain of participant from 0 (no pain) to 10 (very severe pain), on a VAS, where higher scores indicated more severe pain.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. For the assessment of discomfort index, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall arthritis pain of participant from 0 (no pain) to 10 (very severe pain), on a VAS, where higher scores indicated more severe pain.

CHAQ comprised of: disability index and discomfort index, and parent global assessment of overall well-being. For the assessment of discomfort index, the parent/legal guardian or adult caregiver who interacted daily with the participant were required to rate the overall arthritis pain of participant from 0 (no pain) to 10 (very severe pain), on a VAS, where higher scores indicated more severe pain.