A Non-Interventional Study Evaluating Rheumatoid Arthritis Participants Treated With Tocilizumab (RoActemra/Actemra)

Study Overview
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Brief Summary
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This non-interventional study evaluated the use and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis. Eligible participants initiated on tocilizumab treatment according to the approved label were followed for 6 months.

Official Title
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A Multi-Center, Non-Interventional Study to Evaluate Rheumatoid Arthritis (RA) Patients Treated With Tocilizumab (ACROSS)

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants, >/= 18 years of age Moderate to severe rheumatoid arthritis according to the revised (1987) American College of Rheumatology (ACR) criteria Participants in whom the treating physician made the decision to commence tocilizumab treatment (in accordance with the local label); this could include participants who had received tocilizumab treatment within 8 weeks prior to the enrollment visit Exclusion Criteria: Participants who had received tocilizumab more than 8 weeks prior to the enrollment visit Participants who had previously received tocilizumab in a clinical trial or for compassionate use Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever was longer) before starting treatment with tocilizumab History of autoimmune disease or any joint inflammatory disease other than rheumatoid arthritis

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 rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants on Tocilizumab 6 Months After Treatment Initiation |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Dose Modifications |  | 6 months | 
| Percentage of Participants Receiving Tocilizumab After Failing Disease-Modifying Anti-Rheumatic Drugs (DMARDs) |  | 6 months | 
| Percentage of Participants Receiving Tocilizumab After Failing Other Biologic Agents |  | Baseline | 
| Reasons for Dose Modifications |  | 6 months | 
| Percentage of Participants With Dose Interruptions |  | 6 months | 
| Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy |  | 6 months | 
| Percentage of Participants on Tocilizumab Monotherapy at Study Entry |  | 6 months | 
| Disease Activity Score Based on 28-Joint Count (DAS28) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. | 6 months | 
| Percentage of Participants on Combination Therapy Achieving a Response by European League Against Rheumatism (EULAR) Category | Percentage of participants achieving a response by EULAR category, including moderate, good, or no response. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline <-1.2 with a DAS28 score ≤3.2; Moderate response: change from baseline <-1.2 with DAS28 scores >3.2 to ≤ 5.1 or >5.1, or a change from baseline <-0.6 to ≥-1.2 with DAS28 scores ≤3.2 and >3.2 to ≤5.1; No response: change from baseline <-0.6 to ≥-1.2 with DAS28 score >5.1, or a change from baseline ≥-0.6 with DAS28 scores ≤3.2, >3.2 to ≤ 5.1, or >5.1. | 6 months | 
| Percentage of Participants on Monotherapy Achieving a Response by European League Against Rheumatism (EULAR) Category | Percentage of participants achieving a response by EULAR category, including moderate, good, or no response. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline <-1.2 with a DAS28 score ≤3.2; Moderate response: change from baseline <-1.2 with DAS28 scores >3.2 to ≤ 5.1 or >5.1, or a change from baseline <-0.6 to ≥-1.2 with DAS28 scores ≤3.2 and >3.2 to ≤5.1; No response: change from baseline <-0.6 to ≥-1.2 with DAS28 score >5.1, or a change from baseline ≥-0.6 with DAS28 scores ≤3.2, >3.2 to ≤ 5.1, or >5.1. | 6 months | 
| Simplified Disease Activity Index (SDAI) | Simplified Disease Activity Index (SDAI) is an index for measuring disease activity in RA and has a good correlation with the DAS28. The index is calculated using the following formula: SDAI: swollen joint count (SJC28) + tender joint count (TJC28) + physician global assessment (PGA) (10 cm visual analogue scale [VAS]) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligrams/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores range from 0 to 86, with higher scores also indicating increased disease activity. | 6 months | 
| Clinical Disease Activity Index (CDAI) Score | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in RA. The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. | 6 months | 
| Percentage of Participants With American College of Rheumatology (ACR) Response | ACR response was calculated based on total joint count evaluation and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (28 joints) and tender joint count (28 joints) and at least 3 of the following 5 assessments: patient's global assessment of pain, participant's global assessment of disease activity (PGH), physician's global assessment of disease activity (PhGH) (all 3 assessed at 0 [good] to 100 mm [worst] VAS scale); participant assessment of disability measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessed on a 0 to 3 scale, where higher scores represented higher disease activity); acute phase reactant (CRP or ESR). A reduction in the level of and acute phase reactants was considered an improvement. ACR50 and ACR70 require a 50% and 70% improvement from baseline, respectively. | 6 months | 
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) | An AESI includes serious/medically significant infections; opportunistic infections; cases of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), in combination with either elevated bilirubin or clinical jaundice; suspected transmission of an infectious agent by the study drug; myocardial infarction /acute coronary syndrome; gastrointestinal perforations; malignancies; anaphylaxis / hypersensitivity reactions (including injection site reactions); demyelinating disorders; stroke; serious/medically significant bleeding events; or serious/medically significant hepatic events. | 6 months | 
| Patient Global Assessment of Disease Activity Score | The Patient Global Assessment of disease activity provides an overall assessment of how RA affects the participant using a visual analogue score, where 0 indicates they are managing very well and 100 indicates they are managing very poorly. A decrease in the score indicates improvement. | 6 months | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) | The HAQ is a participant self-reported questionnaire for assessing the extent of the participant's functional ability. It consists of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question has 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ scale is an average of all the scores and ranges from 0 to 3, where higher scores represent higher disease activity. | 6 months | 
| Visual Analogue Scale (VAS) for Fatigue | The VAS-fatigue provides an overall assessment of the level of fatigue that the participant is experiencing using a visual analogue score, where 0 indicates no fatigue, and 100 indicates extreme fatigue. A decrease in the score indicates improvement. | 6 months | 
| Visual Analogue Scale (VAS) for Morning Stiffness | Morning stiffness was defined by the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was as limber as he/she would be during a day involving typical activities. Morning stiffness was assessed on a 100 mm VAS, where 0= none and 100= very severe. | 6 months | 
| Visual Analogue Scale (VAS) for Pain | The VAS-Pain provides an overall assessment of the severity of pain that the participant is experiencing using a visual analogue score, where 0 indicates no pain and 100 indicates unbearable pain. A decrease in the score indicates improvement. | 6 months |