A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Biological: Certolizumab Pegol + Methotrexate (MTX)Biological: Placebo + Methotrexate (MTX)
- Registration Number
- NCT01521923
- Lead Sponsor
- UCB Pharma
- Brief Summary
This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for sustaining clinical response achieved in study RA0055 Period 1 \[NCT01519791\]. Subjects entering this study RA0055 Period 2 achieved sustained Low Disease Activity at Week 52 in study RA0055 Period 1.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 359
- Those subjects in previous study RA0055 Period 1 who are in sustained LDA (defined as DAS28[ESR] ≤ 3.2 at Weeks 40 and 52) at Week 52 in previous study RA0055 Period 1
- Those subjects in previous study RA0055 Period 1 who are NOT in sustained LDA (defined as DAS28[ESR] ≤ 3.2 at Weeks 40 and 52) at Week 52 in previous study RA0055 Period 1
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CZP 200 mg Q4W + Methotrexate Certolizumab Pegol + Methotrexate (MTX) - CZP 200 mg Q2W + Methotrexate Certolizumab Pegol + Methotrexate (MTX) - Placebo + Methotrexate Placebo + Methotrexate (MTX) -
- Primary Outcome Measures
Name Time Method Percentage of Subjects With Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) <= 3.2 at Week 104 in RA0055 Period 2 Without Flaring Week 104 in RA0055 Period 2 This Outcome Measure includes all subjects that have a DAS28 \[ESR\] \<= 3.2 from the start of RA0055 Period 2 (Week 52 of RA0055 Period 1) to Week 104 in RA0055 Period 2 without flaring.
- Secondary Outcome Measures
Name Time Method Change From Week 52 in Previous Study RA0055 Period 1 in Modified Total Sharp Score (mTSS) to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.
Percentage of Subjects With Disease Activity Score 28 [ESR] (DAS28 [ESR]) < 2.6 at Week 52 in Previous Study RA0055 Period 1 Who Maintain a DAS28 [ESR] < 2.6 From Week 52 in RA0055 Period 1 Through Week 104 in RA0055 Period 2 Without Flaring From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:
Tender Joint Count (TJC) \<= 1, Swollen Joint Count (SJC) \<= 1 and Patient's Global Assessment of Disease Activity (PtGADA) \<= 10 mm.Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 Good response is defined as:
DAS28\[ESR\] \<= 3.2 and decrease from Baseline by \>1.2;
moderate response is defined as achievement of one of the following:
* DAS28\[ESR\] \<= 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2
* DAS28\[ESR\] \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6
* DAS28\[ESR\] \> 5.1 and decrease from Baseline \>1.2.
LOCF= Last Observation Carried ForwardChange From Baseline in Previous Study RA0055 Period 1 in Modified Total Sharp Score (mTSS) to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.
Change From Baseline in Previous Study RA0055 Period 1 in the Joint Narrowing Score to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The minimum possible score for JSN in all 30 hand joints was 0, the maximum possible score for JSN in all 30 hand joints was 120. The minimum possible score for JSN in all 12 feet joints was 0, the maximum possible score for JSN in all 12 feet joints was 48. Thus, the minimum possible total JSN score for hands and feet was 0, the the maximum possible total JSN score for Hands and feet was 168. Higher values represent greater damage.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 The assessments are based on a 50 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 The assessments are based on a 70 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects With Radiographic Non-progression From Baseline in Previous Study RA0055 Period 1 to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) \<= 0.5.
Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 The assessments are based on a 20 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects With Radiographic Non-progression From Week 52 in Previous Study RA0055 Period 1 to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) \<= 0.5.
Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.Change From Week 52 in Previous Study RA0055 Period 1 in the Joint Erosion Score to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The minimum possible total erosion score for all 32-hand joints was 0, the maximum possible erosion score for all 32-hand joints was 160. The minimum possible total erosion score for all 12-feet joints was 0, the maximum possible erosion score for all 12 feet joints was 120. Thus, the minimum possible total erosion score for hands and feet was 0, the maximum possible total erosion score for hands and feet was 280. Higher values represent greater damage.Percentage of Subjects With Simplified Disease Activity Index (SDAI) <= 3.3 at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.Change From Baseline in Previous Study RA0055 Period 1 in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. DAS28\[ESR\] ranges from 0-10 with higher values representing higher disease activity.
A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline.Change From Baseline in Previous Study RA0055 Period 1 in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.Time to Flare From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Time to flare, defined as an increase of DAS28\[ESR\] \>= 0.6 above Week 52 DAS28\[ESR\] level, having a DAS28\[ESR\] \>= 3.2 and judged by the Investigator as due to RA and all three criteria confirmed at an additional visit two weeks thereafter, from Week 52 onwards.
Data not available as \> 75% of the participants failed to meet flare criteria.Change From Baseline in Previous Study RA0055 Period 1 in the Joint Erosion Score to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The minimum possible total erosion score for all 32-hand joints was 0, the maximum possible erosion score for all 32-hand joints was 160. The minimum possible total erosion score for all 12-feet joints was 0, the maximum possible erosion score for all 12 feet joints was 120. Thus, the minimum possible total erosion score for hands and feet was 0, the maximum possible total erosion score for hands and feet was 280. Higher values represent greater damage.Change From Week 52 in Previous Study RA0055 Period 1 in the Joint Narrowing Score to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The minimum possible score for JSN in all 30 hand joints was 0, the maximum possible score for JSN in all 30 hand joints was 120. The minimum possible score for JSN in all 12 feet joints was 0, the maximum possible score for JSN in all 12 feet joints was 48. Thus, the minimum possible total JSN score for hands and feet was 0, the the maximum possible total JSN score for Hands and feet was 168. Higher values represent greater damage.
Percentage of Subjects With Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) <= 3.2 at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 The Arthritis interference in the last month with household productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).
Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 LDA is defined as achieving a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) \<= 3.2.
DAS28 values range from 2.0 to 10.0 with a higher value indicating a higher disease activity.Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 The ACR/EULAR 2011 remission criteria is defined as:
Tender Joint Count (TJC) \<= 1, Swollen Joint Count (SJC) \<= 1, C-Reactive Protein (CRP) \<= 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) \<= 10 mm.Percentage of Subjects With Clinical Disease Activity Index (CDAI) <= 2.8 at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
Change From Week 52 in Previous Study RA0055 Period 1 in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. DAS28\[ESR\] ranges from 0-10 with higher values representing higher disease activity.
A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline.Change From Baseline in Previous Study RA0055 Period 1 in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined. CDAI ranges from 0-76 with lower scores indicating less disease activity and higher scores indicating higher disease activity.
A negative value in CDAI change from Baseline indicates an improvement from Baseline.Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Normative physical function is defined as HAQ-DI score \<= 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 to 3 with lower scores meaning lower disability.Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.
Only the employed subjects were analyzed.Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of days with no household work in the last month.
Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of days with reduced household work productivity in the last month.
Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of days missed of family/social/leisure activities in the last month.
Change From Week 52 in Previous Study RA0055 Period 1 in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined. CDAI ranges from 0-76 with lower scores indicating less disease activity and higher scores indicating higher disease activity.A negative value in CDAI change from Baseline indicates an improvement from Baseline.
Change From Week 52 in Previous Study RA0055 Period 1 in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055 Period 2 From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.Change From Baseline in Previous Study RA0055 Period 1 in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 104 in RA0055 Period 2 From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2 BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue), whereas the score for each dimension is different due to the varied number of questions (0 -22 for physical, 0- 21 for living, 0- 15 for cognition, and 0- 12 for emotion). A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.
Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of work days missed in the last month for employed subjects.
Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of work days with reduced productivity in the last month for employed subjects.
Only the employed subjects were analyzed.Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 Week 104 in RA0055 Period 2 Number of days with hired outside help days in the last month.
Trial Locations
- Locations (178)
207
🇺🇸Albuquerque, New Mexico, United States
189
🇺🇸Charleston, South Carolina, United States
167
🇺🇸Duncansville, Pennsylvania, United States
284
🇦🇷Rosario, Argentina
217
🇺🇸Allen, Texas, United States
65
🇧🇪Yvoir, Belgium
124
🇨🇿Bruntal, Czechia
108
🇨🇿Brno, Czechia
2
🇦🇺Herson, Queensland, Australia
195
🇺🇸Bethlehem, Pennsylvania, United States
279
🇦🇷San Juan, Argentina
291
🇦🇷Tucuman, Argentina
38
🇨🇿Hradec Kralove, Czechia
47
🇪🇸Madrid, Spain
37
🇨🇿Praha, Czechia
27
🇬🇧London, United Kingdom
67
🇵🇱Elblag, Poland
21
🇭🇺Budapest, Hungary
297
🇨🇴Bucaramanga, Colombia
77
🇸🇪Stockholm, Sweden
105
🇬🇧Dudley, United Kingdom
63
🇪🇸Santiago de Compostela, Spain
113
🇩🇪Berlin, Germany
76
🇸🇪Göteborg, Sweden
75
🇸🇪Uppsala, Sweden
32
🇮🇪Limerick, Ireland
80
🇬🇧Sheffield, United Kingdom
93
🇪🇸Coruna, Spain
123
🇸🇪Malmö, Sweden
125
🇬🇧Cannock, United Kingdom
177
🇺🇸Hagerstown, Maryland, United States
223
🇺🇸Houston, Texas, United States
183
🇺🇸Clarksburg, West Virginia, United States
166
🇺🇸Plantation, Florida, United States
224
🇺🇸South Bend, Indiana, United States
257
🇺🇸Hemet, California, United States
203
🇺🇸Tupelo, Mississippi, United States
256
🇺🇸Reno, Nevada, United States
5
🇦🇺Fitzroy, Victoria, Australia
162
🇺🇸Dallas, Texas, United States
206
🇺🇸Houston, Texas, United States
175
🇺🇸Nassau Bay, Texas, United States
174
🇺🇸Glendale, Wisconsin, United States
6
🇦🇺Coffs Harbour, New South Wales, Australia
232
🇺🇸Miami, Florida, United States
180
🇺🇸Mobile, Alabama, United States
197
🇺🇸San Antonio, Texas, United States
236
🇺🇸Durham, North Carolina, United States
215
🇺🇸Cedar Rapids, Iowa, United States
245
🇺🇸Middleburg Heights, Ohio, United States
168
🇺🇸Wyomissing, Pennsylvania, United States
185
🇺🇸Amarillo, Texas, United States
161
🇺🇸Austin, Texas, United States
178
🇺🇸Corpus Christi, Texas, United States
158
🇺🇸Mesquite, Texas, United States
184
🇺🇸Houston, Texas, United States
249
🇺🇸Plano, Texas, United States
233
🇺🇸Kennewick, Washington, United States
7
🇦🇺Perth, Western Australia, Australia
209
🇺🇸Birmingham, Alabama, United States
243
🇺🇸Phoenix, Arizona, United States
241
🇺🇸Oklahoma City, Oklahoma, United States
186
🇺🇸Portland, Oregon, United States
170
🇺🇸Huntsville, Alabama, United States
234
🇺🇸Paradise Valley, Arizona, United States
251
🇺🇸Tucson, Arizona, United States
160
🇺🇸Covina, California, United States
159
🇺🇸Los Angeles, California, United States
201
🇺🇸San Leandro, California, United States
202
🇺🇸Upland, California, United States
172
🇺🇸Whittier, California, United States
190
🇺🇸Fort Lauderdale, Florida, United States
196
🇺🇸Jupiter, Florida, United States
213
🇺🇸Naples, Florida, United States
214
🇺🇸Ocala, Florida, United States
192
🇺🇸Sarasota, Florida, United States
200
🇺🇸Vero Beach, Florida, United States
226
🇺🇸Coeur d'Alene, Idaho, United States
244
🇺🇸Springfield, Illinois, United States
191
🇺🇸Wichita, Kansas, United States
210
🇺🇸Wichita, Kansas, United States
198
🇺🇸Eagan, Minnesota, United States
179
🇺🇸Saint Louis, Missouri, United States
181
🇺🇸Lincoln, Nebraska, United States
228
🇺🇸Clifton, New Jersey, United States
242
🇺🇸Plainview, New York, United States
176
🇺🇸Brooklyn, New York, United States
227
🇺🇸Rochester, New York, United States
82
🇸🇪Huddinge, Sweden
106
🇸🇪Lund, Sweden
56
🇬🇧Leeds, United Kingdom
121
🇬🇧London, United Kingdom
119
🇬🇧York, United Kingdom
79
🇫🇷Strasbourg, France
52
🇩🇪Bad Doberan, Germany
54
🇮🇪Dublin, Ireland
41
🇮🇹Verona, Italy
286
🇲🇽Guadalajara, Mexico
292
🇲🇽Mexico D.F., Mexico
247
🇺🇸Glendale, Arizona, United States
237
🇺🇸Orange Park, Florida, United States
8
🇦🇺Woodville South, South Australia, Australia
50
🇦🇹Wien, Austria
194
🇨🇦Trois-rivieres, Quebec, Canada
188
🇨🇦Montreal, Quebec, Canada
293
🇨🇴Bogota, Colombia
298
🇨🇴Medellin, Colombia
199
🇺🇸Kalamazoo, Michigan, United States
163
🇺🇸Palm Harbor, Florida, United States
204
🇺🇸Hendersonville, Tennessee, United States
1
🇦🇺Maroochydore, Queensland, Australia
276
🇦🇷Buenos Aires, Argentina
88
🇫🇷Montpellier Cedex 5, France
70
🇩🇪Frankfurt, Germany
69
🇩🇪Rheine, Germany
59
🇩🇪Zerbst, Germany
78
🇲🇨Monaco, Monaco
99
🇵🇱Krakow, Poland
92
🇵🇱Poznan, Poland
205
🇺🇸Columbia, South Carolina, United States
44
🇵🇱Wroclaw, Poland
24
🇷🇴Iasi, Romania
165
🇺🇸Paradise Valley, Arizona, United States
34
🇫🇷Orleans, France
255
🇺🇸Orlando, Florida, United States
229
🇺🇸Lebanon, New Hampshire, United States
303
🇨🇴Barranquilla, Colombia
4
🇦🇺Geelong, Victoria, Australia
3
🇦🇺Malvern, Victoria, Australia
120
🇩🇪Berlin, Germany
51
🇧🇪Brussels, Belgium
36
🇧🇪Kortrijk, Belgium
240
🇨🇦Kelowna, British Columbia, Canada
271
🇨🇴Medellin, Colombia
132
🇩🇪Ratingen, Germany
114
🇩🇪Würzburg, Germany
86
🇭🇺Eger, Hungary
126
🇧🇪Gilly, Belgium
272
🇨🇴Bogota, Colombia
299
🇨🇴Bogota, Colombia
288
🇨🇴Chia, Colombia
16
🇫🇷Le Kremlin Bicetre, France
85
🇫🇷Le Mans, France
17
🇩🇪Bayreuth, Germany
127
🇩🇪Lingen, Germany
19
🇭🇺Veszprem, Hungary
281
🇲🇽Durango, Mexico
118
🇨🇭Fribourg, Switzerland
235
🇨🇦Hamilton, Ontario, Canada
71
🇩🇪Hamburg, Germany
18
🇭🇺Budapest, Hungary
89
🇩🇪Erfurt, Germany
81
🇩🇪Hildesheim, Germany
131
🇭🇺Szolnok, Hungary
33
🇮🇪Cork, Ireland
115
🇮🇹Ferrara, Italy
280
🇲🇽Monterrey, Mexico
111
🇷🇴Bucharest, Romania
22
🇷🇴Bucharest, Romania
57
🇷🇴Lasi, Romania
61
🇩🇪München, Germany
53
🇩🇪Planegg, Germany
49
🇩🇪Rendsburg, Germany
110
🇭🇺Szombathely, Hungary
122
🇮🇹Milano, Italy
40
🇮🇹Reggio Emilia, Italy
302
🇲🇽Merida, Mexico
42
🇳🇱Leiden, Netherlands
128
🇵🇱Bydgoszcz, Poland
74
🇵🇱Torun, Poland
58
🇷🇴Brasov, Romania
26
🇷🇴Bucharest, Romania
68
🇨🇭St. Gallen, Switzerland
72
🇮🇹Roma, Italy
294
🇲🇽San Luis Potosi, Mexico
100
🇵🇱Warszawa, Poland
25
🇷🇴Bucharest, Romania
238
🇺🇸Lake Mary, Florida, United States