An Observational Study of RoActemra/Actemra (Tocilizumab) in Monotherapy in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This multicenter observational study will evaluate the use of RoActemra/Actemra (tocilizumab) in monotherapy in patients with active moderate to severe rheumatoid arthritis unable to use methotrexate. Eligible patients initiated on RoActemra/Actemra treatment will be followed for 6 months.

Official Title
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HAQIMONO a Non-interventional National Multicenter Study, Observing RA Patients Treated With Tocilizumab in Mono-therapy, i.e. Without Combination With DMARD

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 Moderate to severe rheumatoid arthritis according to the revised (1987) ACR criteria Patients who for any reason do not take methotrexate and for whom the treating physician has made a decision to prescribe RoActemra/Actemra as monotherapy; patients who commenced RoActemra/Actemra as monotherapy within 8 weeks prior to the enrolment visit may be included Concomitant treatment with non-steroidal anti-inflammatory drug (NSAID) or corticosteroids (orally or intra-articularly) is allowed Exclusion Criteria: Patients who have received RoActemra/Actemra more than 8 weeks prior to enrolment visit Previous RoActemra/Actemra treatment in a clinical trial or for compassionate use Concomitant DMARD treatment for rheumatoid arthritis (e.g. hyroxychloroquine, sulfasalazine, methotrexate, leflunomide, gold compounds, cyclosporine) Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before starting RoActemra/Actemra treatment 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 |
| --- | --- |
| Cohort<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants on Tocilizumab Treatment at Month 6 |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Dose Modifications of Tocilizumab | Dose modification is any change in dose; this also included participants who stopped treatment with tocilizumab. | Baseline to Month 6 | 
| Swollen Joint Count (SJC) | Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of swollen joints compared to baseline indicates improvement. | Baseline, Month 3, Month 6 | 
| Tender Joint Count (TJC) | Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of tender joints compared to baseline indicates improvement. | Baseline, Month 3, Month 6 | 
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) | DAS28-4 (CRP) was calculated from the SJC and TJC using the 28 joints count, CRP (milligram per liter [mg/L]) and patient global assessment (PtGA) of disease activity (measured on a 0 to 100 millimeter [mm] Visual Analog Scale [VAS]) where 0=no disease activity and 100=worst disease activity). DAS28-4 (CRP) was calculated using the following formula: DAS28-4 (CRP) = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*PtGA + 0.96. Total score range: 0 to 10, higher score indicated more disease activity. DAS28-4 (CRP) less than or equal to (<= 3.2) implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (CRP) less than (<) 2.6 = clinical remission. | Baseline, Month 3, Month 6 | 
| Percentage of Participants Achieving Clinical Remission Based on DAS28-4 (CRP) | DAS28-4 (CRP) was calculated from the SJC and TJC using the 28 joints count, CRP (mg/L) and PtGA of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity). DAS28-4 (CRP) was calculated using the following formula: DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*PtGA + 0.96. Total score range: 0 to 10, higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 implied low disease activity and > 3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (CRP) < 2.6 = clinical remission. | Month 3 and Month 6 | 
| Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) | DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (millimeter per hour [mm/hour]), and PtGA of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity). DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*PtGA. Total score range: 0-10, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = clinical remission. | Baseline, Month 3, Month 6 | 
| Percentage of Participants Achieving Clinical Remission Based on DAS28-4 (ESR) | DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and PtGA of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity). DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*PtGA. Total score range: 0-10, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = clinical remission. | Month 3 and Month 6 | 
| Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28-4 (CRP) | The DAS28-4 (CRP) [described in Outcome Measure 5] based EULAR response criteria were used to measure individual response as good, moderate, or no response depending on the extent of change from baseline in DAS28 score and the level of disease activity (low, moderate or high) reached. Good responders: change from baseline >1.2 with DAS28 <= 3.2; moderate responders: change from baseline >1.2 with DAS28 in the range of >3.2 to <=5.1 or change from baseline in the range of >0.6 to <=1.2 with DAS28 in the range of >3.2 to <=5.1 or change from baseline >1.2 with DAS28 >5.1 or change from baseline in the range of >0.6 to <=1.2 with DAS28 <=3.2; non-responders: change from baseline <= 0.6 or change from baseline in the range of >0.6 to <=1.2 with DAS28 >5.1 or change from baseline <=0.6 with DAS28 <=3.2 or in the range of >3.2 to <=5.1. | Month 3 and Month 6 | 
| Percentage of Participants With EULAR Response Based on DAS28-4 (ESR) | The DAS28-4 (ESR) [described in Outcome Measure 7] based EULAR response criteria were used to measure individual response as good, moderate, or no response depending on the extent of change from baseline in DAS28 score and the level of disease activity (low, moderate or high) reached. Good responders: change from baseline >1.2 with DAS28 <= 3.2; moderate responders: change from baseline >1.2 with DAS28 in the range of >3.2 to <=5.1 or change from baseline in the range of >0.6 to <=1.2 with DAS28 in the range of >3.2 to <=5.1 or change from baseline >1.2 with DAS28 >5.1 or change from baseline in the range of >0.6 to <=1.2 with DAS28 <=3.2; non-responders: change from baseline <= 0.6 or change from baseline in the range of >0.6 to <=1.2 with DAS28 >5.1 or change from baseline <=0.6 with DAS28 <=3.2 or in the range of >3.2 to <=5.1. | Month 3 and Month 6 | 
| Simplified Disease Activity Index (SDAI) | The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and physician global assessment (PGA) assessed on 0-10 centimeter (cm) VAS; 0 = no disease activity and 10 = worst disease activity, and CRP (mg/dL). SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. | Baseline, Month 3, Month 6 | 
| Percentage of Participants Achieving Clinical Remission Based on SDAI | The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-10 cm VAS; 0 = no disease activity and 10 = worst disease activity, and CRP (mg/dL). SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. | Month 3 and Month 6 | 
| Clinical Disease Activity Index (CDAI) | The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-10 cm VAS; 0 = no disease activity and 10 = worst disease activity. CDAI total score = 0-76. CDAI <= 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity. | Baseline, Month 3, Month 6 | 
| Percentage of Participants Achieving Clinical Remission Based on CDAI | The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-10 cm VAS; 0 = no disease activity and 10 = worst disease activity. CDAI total score = 0-76. CDAI <= 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity. | Month 3 and Month 6 | 
| Number of Participants With an American College of Rheumatology (ACR) Response | ACR response: improvement in tender or swollen joint counts and improvement in 3 of the following 5 criteria: 1) PGA of disease activity, 2) PtGA of disease activity, 3) patient's assessment of pain, 4) patient's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. ACR response is based on 66/68 total joint count. | Baseline to Month 6 | 
| Patient Global Assessment (PtGA) of Disease Activity Score | Patient Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity. | Baseline, Month 3, Month 6 | 
| Physician Global Assessment (PGA) of Disease Activity | Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity. | Baseline, Month 3, Month 6 | 
| Percentage of Participants in a PGA of Disease Activity Score Category | A categorical scale (Lickert scale) with the following categories: none, mild, moderate, severe and maximal was used to evaluate disease activity in clinical practice. | Baseline, Month 3, Month 6 | 
| Patient Global Assessment of Pain | Patient Global Assessment of Pain was assessed using a 100 mm VAS (0 to 100) where 0 = no pain to 100 = worst possible pain. | Baseline, Month 3, Month 6 | 
| Percentage of Participants With Morning Stiffness | The percentage of participants with morning stiffness (yes, no, or do not know) was assessed at each visit. | Baseline, Month 3, Month 6 | 
| Percentage of Participants With Duration of Morning Stiffness | Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness. Duration was recorded as less than (<) 30 minutes, 30 to 60 minutes, 60 to 120 minutes, 120 to 240 minutes, more than (>) 240 minutes, or whole day. | Baseline, Month 3, Month 6 | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Months 3 and 6 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. | Baseline, Month 3 and Month 6 | 
| Percentage of Participants With Concomitant Corticosteroids Treatment |  | Baseline to Month 6 | 
| Number of Participants With Use of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) During the Study |  | Baseline to Month 6 |