Multi-country Post-Marketing Observational Study on Maintenance of Effectiveness of Adalimumab (Humira®) in Patients With Ankylosing Spondylitis and Psoriatic Arthritis

Study Overview
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Brief Summary
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This 12-month postmarketing observational study (PMOS) was a prospective, single-arm, multicenter, multi-country study, with follow-up visits at 3, 6, 9, and 12 months after the initial baseline visit. The study was conducted to determine the long-term effectiveness of treatment with adalimumab in routine clinical use in participants with Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA) in Central and Eastern European Countries.

Detailed Description
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Additional study objectives were to evaluate AS and PsA with regard to extra-articular manifestations (EAMs), functional status, the use of concomitant nonsteroidal anti-inflammatory medication, and work productivity impairment. In addition, the Ankylosing Spondylitis Disease Activity Score (ASDAS), a new disease activity index in AS, was measured in parallel with the standard Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score to assess the effectiveness of adalimumab in treating axial symptoms.

Official Title
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Multicountry Post-Marketing Observational Study on Maintenance of Effectiveness of Adalimumab in Patients With Ankylosing Spondylitis and Psoriatic Arthritis

Conditions
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Psoriatic Arthritis, Ankylosing Spondylitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be enrolled in this Postmarketing observational study PMOS if they fulfill all of the below criteria: Adult patients with diagnosis of Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA). Eligible for adalimumab therapy according to the local product label and prescription/reimbursement guidelines. Have been prescribed adalimumab within a maximum of one (1) month prior to the study enrolment. Have negative result of Tuberculosis (TB) screening test or TB prophylaxis as per local guidelines. Are willing to provide Authorization to the investigator to use and/or disclose personal and/or health data, or to provide Informed Consent if requested by the Local Regulations, before entry into the study. Exclusion Criteria: Patients fulfilling below exclusion criteria will not be eligible for this Postmarketing study (PMOS): 1. Meet contraindications for treatment with adalimumab as outlined in the latest version of the local Summary of Product Characteristics (SmPC)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ankylosing Spondylitis<br>Participants with a diagnosis of ankylosing spondylitis | |
| Psoriatic Arthritis<br>Participants with a diagnosis of psoriatic arthritis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a 50% or More Decrease in Bath Ankylosing Spondylitis Daily Activity Index (BASDAI) Score at 12 Months Relative to Baseline | The BASDAI score was calculated using a questionnaire with 6 questions that the participants completed by marking responses on a 10-centimeter visual analog scale ranging from 0 (none) to 10 (very severe) regarding severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. A positive response was defined as a 50% or more decrease in the BASDAI score at 12 months as compared to baseline. | Baseline (Visit 0) to 12 months | 
| Percentage of Participants With a Disease Activity Score 28 (DAS28) Decrease ≥1.2 at 12 Months Relative to Baseline | The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. | Baseline (Visit 0) to 12 months | 
| Percentage of Participants With Active Axial Symptoms in Remission | The Ankylosing Spondylitis Disease Score (ASDAS) tool is a self-administered questionnaire plus an objective laboratory evaluation. The questionnaire covers disease activity, back pain, duration of morning stiffness and peripheral pain/swelling assessed on a visual analogue scale (from 0 to 10 cm) or on a numerical rating scale (from 0 to 10). The laboratory parameter is a measurement of C-reactive protein (mg/L) or erythrocyte sedimentation rate (mm/h). Remission was defined as ASDAS <1.3 at 12 months. | Baseline (Visit 0) to 12 months | 
| Percentage of Participants With Peripheral Symptoms in Remission | The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. Remission was defined as DAS28 ≤2.6 at 12 months. | Baseline (Visit 0) to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score (in Case of Axial Symptoms) and/or Disease Activity Score/28 Joints (DAS28) (in Case of Peripheral Symptoms) in Participants With Ankylosing Spondylitis | The BASDAI score was calculated using a questionnaire with 6 questions that the participants completed by marking responses on a 10-centimeter visual analog scale ranging from 0 (none) to 10 (very severe) regarding severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. A positive response was defined as a 50% or more decrease in the BASDAI score at 12 months as compared to baseline. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C- reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. | Baseline (Visit 0) to 12 months | 
| Mean Change in Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS tool is a self-administered questionnaire plus an objective laboratory evaluation. The questionnaire covers disease activity, back pain, and peripheral pain/swelling assessed on a visual analogue scale (from 0 (normal) to 10 (extreme pain or disability) cm) and duration of morning stiffness on a numerical rating scale (from 0 to 10, with 0 being none and 10 representing a duration of 2 hours or longer). The laboratory parameter is a measurement of C-reactive protein (mg/L) (CRP) or erythrocyte sedimentation rate (mm/h) (ESR). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and either CRP or ESR values) are combined to yield a score ranging from 0 to no defined upper limit. Remission is defined as ASDAS score <1.3. Clinically important improvement is defined as a change ≥ 1.1 units, and major improvement is defined as a change ≥ 2.0 units. | Baseline (Visit 0) to 12 months | 
| Correlation Between Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) in Participants With Ankylosing Spondylitis | BASDAI score (ranging from 0 to 10) was calculated using a questionnaire. Participants marked responses on a 10 cm visual analog scale ranging from 0 (none) to 10 (very severe) regarding fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. A positive response was defined as a 50% or more decrease in the BASDAI score at 12 months as compared to baseline. ASDAS is a self-administered questionnaire plus an objective laboratory evaluation. The questionnaire covers disease activity, back pain, duration of morning stiffness and peripheral pain/swelling assessed on a visual analogue scale (from 0 to 10 cm) or on a numerical rating scale (from 0 to 10). The laboratory parameter is a measurement of C-reactive protein (mg/L) or erythrocyte sedimentation rate (mm/h). Spearman's rank correlation coefficient (CC) was calculated for BASDAI vs. ASDAS(subscript)CRP(subscript) and BASDAI vs. ASDAS(subscript)ESR(subscript ). | Baseline (Visit 0) to 12 months | 
| Predictors of Maintained Treatment Response and Remission in Participants With Ankylosing Spondylitis | A mathematical technique called logistic regression was performed to identify factors that could be used to predict maintained treatment response and remission. The following baseline variables were used in the logistic regression analyses: age, gender, disease of interest, result of tuberculosis screening, time since diagnosis and extra-articular manifestations (symptoms and diseases that occur in parts of the body other than joints) at baseline. The BASDAI score at baseline was forced to serve as a predictor in each model. | Baseline (Visit 0) to 12 months | 
| Mean Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score (in Case of Peripheral Symptoms) or Bath Ankylosing Spondylitis Functional Index (BASFI) Score (in Case of Axial Symptoms) in Participants With Ankylosing Spondylitis | HAQ-DI consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, with a higher score representing a high-dependency disability. The minimal clinically important difference defined for the HAQ-DI is ≥0.22. HAQ-DI remission, indicating normal physical function, is defined as HAQ-DI < 0.5. The BASFI is a set of 10 questions designed to determine the degree of functional limitation in those with AS. A visual analogue scale (with 0 being easy and 10 impossible) is used. The BASFI score ranges from 0 to 10 and is derived as the mean of the single items. A higher score indicates a higher impairment of functioning. | Baseline (Visit 0) to 12 months | 
| Mean Frequency of Extra-articular Manifestations (EAMs) | Extra-articular manifestations (EAMs) are symptoms and diseases that occur in parts of the body other than joints. The number of EAMs was determined at each study visit. These included the presence of enthesitis (inflammation of ligaments and/or tendons at the site of insertion into bones), uveitis (inflammation of the middle layer of the eye), psoriasis (a skin condition that causes itchy or sore patches of thick, red skin with silvery scales), and Inflammatory bowel disease (Crohn's disease or ulcerative colitis). | Baseline (Visit 0) to 12 months | 
| Duration of Treatment With Adalimumab | The duration of treatment with adalimumab was calculated separately for participants who discontinued the medication during the study and for those who did not. | Baseline (Visit 0) to 12 months | 
| Percentage of Participants Whose Co-medication With Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Was Stopped During the Study | Participants were surveyed at each study visit for their use of NSAID medication. | Baseline (Visit 0) to 12 months | 
| Mean Change in Individual Components of the Work Productivity and Activity Impairment Specific Health Problem Questionnaire in Participants With Ankylosing Spondylitis | Work Productivity and Activity Impairment (WPAI) Questionnaire is a quantitative assessment of the amount of absenteeism, presenteeism, total work productivity impairment, and total activity impairment attributable to a specific health problem (WPAI-SHP), expressed as a percentage. Participants were queried regarding their current employment status, hours missed from work because of problems associated with their AS, hours missed from work because of any other reason, number of hours worked, how much AS affected work productivity (0=AS had no effect,10= AS completely prevented me from working), and how much AS affected ability to do regular daily activities, other than work at a job (0= AS had no effect, 10= AS completely prevented me from doing my daily activities) in the past 7 days. | Baseline (Visit 0) to 12 months | 
| Change in the Percentage of Ankylosing Spondylitis Participants Who Have Paid Work | Working status (Working full-time, working part-time, working at home, unemployed but seeking work, work disabled, retired, student) was documented at each study visit. | Baseline (Visit 0) to 12 months | 
| Mean Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score (in Case of Axial Symptoms) and/or Disease Activity Score/28 Joints (DAS28) (in Case of Peripheral Symptoms) in Participants With Psoriatic Arthritis | The BASDAI score was calculated using a questionnaire with 6 questions that the participants completed by marking responses on a 10-centimeter visual analog scale ranging from 0 (none) to 10 (very severe) regarding severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. A positive response was defined as a 50% or more decrease in the BASDAI score at 12 months as compared to baseline. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C- reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. | Baseline (Visit 0) to 12 months | 
| Correlation Between Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) in Participants With Psoriatic Arthritis | BASDAI score (ranging from 0 to 10) was calculated using a questionnaire. Participants marked responses on a 10 cm visual analog scale ranging from 0 (none) to 10 (very severe) regarding fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. A positive response was defined as a 50% or more decrease in the BASDAI score at 12 months as compared to baseline. ASDAS score consists of a self-administered questionnaire plus an objective laboratory evaluation. The questionnaire covers disease activity, back pain, duration of morning stiffness and peripheral pain/swelling assessed on a visual analogue scale (from 0 to 10 cm) or on a numerical rating scale (from 0 to 10). The laboratory parameter is a measurement of C-reactive protein (mg/L) or erythrocyte sedimentation rate (mm/h). Spearman's rank correlation coefficient (CC) was calculated for BASDAI vs. ASDAS(subscript)CRP(subscript) and BASDAI vs. ASDAS(subscript)ESR(subscript). | Baseline (Visit 0) to 12 months | 
| Predictors of Maintained Treatment Response and Remission in Participants With Psoriatic Arthritis | A mathematical technique called logistic regression was performed to identify factors that could be used to predict maintained treatment response and remission. The following baseline variables were used in the logistic regression analyses: age, gender, disease of interest, result of tuberculosis screening, time since diagnosis and extra-articular manifestations (symptoms and diseases that occur in parts of the body other than joints) at baseline. The BASDAI score at baseline was forced to serve as a predictor in each model. | Baseline (Visit 0) to 12 months | 
| Mean Change in Health Assessment Questionnaire Disability Index ( HAQ-DI) Score (in Case of Peripheral Symptoms) or Bath Ankylosing Spondylitis Functional Index (BASFI) Score (in Case of Axial Symptoms) in Participants With Psoriatic Arthritis | HAQ-DI consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, with a higher score representing a high-dependency disability. The minimal clinically important difference defined for the HAQ-DI is ≥0.22. HAQ-DI remission, indicating normal physical function, is defined as HAQ-DI < 0.5. The BASFI is a set of 10 questions designed to determine the degree of functional limitation in those with AS. A visual analogue scale (with 0 being easy and 10 impossible) is used. The BASFI score ranges from 0 to 10 and is derived as the mean of the single items. A higher score indicates a higher impairment of functioning. | Baseline (Visit 0) to 12 months | 
| Mean Change in Individual Components of the Work Productivity and Activity Impairment Specific Health Problem Questionnaire in Participants With Psoriatic Arthritis | The Work Productivity and Activity Impairment (WPAI) Questionnaire is a quantitative assessment of the amount of absenteeism, presenteeism, total work productivity impairment, and total activity impairment attributable to a specific health problem (WPAI-SHP), expressed as a percentage. Participants were queried regarding their current employment status, hours missed from work because of problems associated with their PsA, hours missed from work because of any other reason, number of hours worked, how much PsA affected work productivity (0= PsA had no effect,10= PsA completely prevented me from working), and how much PsA affected ability to do regular daily activities, other than work at a job (0= PsA had no effect, 10= PsA completely prevented me from doing my daily activities) in the past 7 days. | Baseline (Visit 0) to 12 months | 
| Change in the Percentage of Psoriatic Arthritis Participants Who Have Paid Work | Working status (Working full-time, working part-time, working at home, unemployed but seeking work, work disabled, retired, student) was documented at each study visit. | Baseline (Visit 0) to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-marketing observational study (PMOS) Protocol, Effectiveness of Adalimumab (HUMIRA®), Psoriatic Arthritis, Ankylosing Spondylitis