An Observational Study on RoActemra/Actemra (Tocilizumab) in Clinical Practice in Patients With Rheumatoid Arthritis (TRUST)

Study Overview
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Brief Summary
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This observational study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in clinical practice in patients with moderate to severe rheumatoid arthritis. Data will be collected from patients for the 12 months following the first infusion of RoActemra/Actemra.

Official Title
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Rheumatoid Arthritis Patients Treated With Tocilizumab in Real Clinical Practice: Effectiveness and Safety (TRUST Study)

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria Initiated on RoActemra/Actemra treatment according to the Summary of Product Characteristics not more than 6 months before opening of study center Exclusion Criteria: Current serious infection Hypersensitivity to the active component or any of the excipients Pregnant women

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 |
| --- | --- |
| Tocilizumab<br>Participants with moderate to severe Rheumatoid arthritis (RA) who had received RoActemra [Tocilizumab (TCZ)] treatment for 6 months prior to initiation of study and are inadequate responders to Disease Modifying Anti-Rheumatic Drugs (DMARDs) and anti-Tumor Necrosis Factors (anti-TNFs) agents were observed. Participants received treatment with TCZ with dose of 8 milligrams per kilogram (mg/kg) body weight, intravenously once every 4 weeks for 12 months according to European Union (EU) approved dosage, and Summary of Product Characteristics (SmPC). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Low Disease Activity After 6 Months of Treatment | Low disease activity is defined as a disease activity score based on 28 joint count (DAS28) score lesser or equal to (</=) 3.2. The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3. Erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) measurement, 4. Participant's judgement on his own overall health status expressed by a visual analogue scale (VAS). The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. Percentage of participants with low disease activity was reported. | Up to 12 months | 
| Percentage of Participants Achieving Disease Remission After 6 Months of Treatment | Disease remission is defined as a DAS28 score < 2.6. The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3. ESR or CRP measurement, 4. Participant's judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation. Percentage of participants with disease remission was reported. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score of Disease Activity Based on 28 Joint Count in Participants on Monotherapy With Tocilizumab | The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3.ESR or CRP measurement, 4. Participant's judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation. | Baseline (Month 0), Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Mean Score of Fatigue Based on Visual Analogue Scale in Participants on Monotherapy With Tocilizumab | VAS for fatigue is a 100 mm scale for participant's assessment of their current level of fatigue. The '0 'mm corresponds to no perception of fatigue, '100 mm' is the maximum level of fatigue that may be perceived. Mean score of VAS fatigue in participants were reported. | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Mean Score of Health Assessment Questionnaire in Participants on Monotherapy With Tocilizumab | The health assessment questionnaire (HAQ) is a participant-completed questionnaire specific for RA, recommended by the American college of Rheumatology for the evaluation of quality of life. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. There are 4 possible responses for each question: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do. To calculate HAQ, the participant must have a component set score for at least 6 of 8 component set. The HAQ is the sum of the scores, divided by the number of component set that have a score (in range 6-8) for a total possible score of minimum/maximum i.e., 0 (best) to 3 (worst). | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Number of Participants With Concomitant Medications | Number of participants treated with at least one concomitant medication i.e., corticosteroid (Prednisone, Methyl prednisolone) was reported. | Up to 12 months | 
| Percentage of Participants Discontinuing Treatment With Tocilizumab | The percentage of participants who prematurely discontinued treatment with TCZ during the study period was reported. | Up to 12 months | 
| Number of Participants With Any Adverse Events and Serious Adverse Events | An adverse event (AE) was defined as any untoward medical occurrence in a participant who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. | Up to 12 months | 
| Percentage of Participants Still on Tocilizumab Treatment Till 12 Months After the 1st Infusion | Percentage of participants who continued treatment till 12 months after the first infusion with TCZ was reported. | Up to 12 months | 
| Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Second Metacarpo-phalangeal Joint of Right Hand. | The presence and severity of synovial hyperplasia (SH) and joint effusion (JE) of second metacarpo-phalangeal (MCP) joint of right hand was determined by ultrasound examination. According to the method proposed by Naredo, synovial hyperplasia and joint effusion were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra articular surface). | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Third Metacarpo-phalangeal Joint of Right Hand. | The presence and severity of SH and JE of third MCP joint of right hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of third MCP joint of right hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intraarticular surface). | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Second Metacarpo-phalangeal Joint of Left Hand | The presence and severity of SH and JE of second MCP joint of left hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of second MCP joint of left hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra-articular surface). | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Third Metacarpo-phalangeal Joint of Left Hand. | The presence and severity of SH and JE of third MCP joint of left hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of third MCP joint of left hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra-articular surface). | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Mean Disease Activity Score Based on 28 Joint Count Score in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents | The DAS28 index applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints) 3. ESR or CRP measurement, 4. Participant's judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation. The mean DAS28 scores were evaluated after the first infusion of TCZ in two different sub populations: participants with inadequate response (IR) to DMARD (DMARD-IR: group A) or to DMARD and anti-TNF drugs (DMARD + anti-TNF-IR: group B). Data allowing the evaluation of DAS28 was available for 81 participants in DMARD-IR group and 203 participants in DMARD + anti-TNF-IR group. | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Mean Score of Fatigue Based on Visual Analogue Scale in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents | VAS for fatigue is a 100 mm scale for participant's assessment of their current level of fatigue: 0 mm corresponds to no perception of fatigue; 100 mm is the maximum that may be perceived. The mean VAS fatigue scores were evaluated after the first infusion of TCZ in two different sub populations, classified according to the previous pharmacological treatment: participants with inadequate response to DMARD (DMARD-IR: group A) or to DMARD and anti-TNF drugs (DMARD + anti-TNF-IR: group B). Data allowing the evaluation of fatigue (VAS) was available for 45 participants in DMARD-IR group and 113 participants in DMARD + anti-TNF-IR group. | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 | 
| Mean Score of Health Assessment Questionnaire in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents | The HAQ is a participant-completed questionnaire specific for RA, recommended by the American college of Rheumatology for the evaluation of quality of life. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. There are 4 possible responses for each question: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do. To calculate HAQ, participant must have a component set score for at least 6 of 8 component set. The HAQ is the sum of the scores, divided by the number of component set that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). Data allowing the evaluation of HAQ was available for 73 participants in DMARD-IR group and 157 participants in DMARD + anti-TNF-IR group. | Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12 |