A Non-Interventional Study of RoActemra/Actemra in Patients With Moderate to Severe Rheumatoid Arthritis

Systemic manifestations of RA at baseline included anemia, fatigue, conventional risk factor(s) for cardiovascular disease, C-reactive protein (CRP) above upper limit of normal rheumatoid nodules, rheumatoid vasculitis, and interstitial lung disease.

DMARDs exposure was evaluated for all participants. "Prior DMARDs treatment" included participants, who were treated with DMARDs 8 weeks according to physician's discretion before being included in the study. "DMARDs treatment at baseline" included participants who were receiving DMARDs when they were included in the study and continued with this concomitant medication in addition to TCZ.

DMARDs exposure was evaluated for all participants. DMARDs treatment at baseline included participants, who were receiving DMARDs when they were included in the study and discontinued at baseline and not used as concomitant medication to TCZ.

The duration of previous biologic RA treatments was classified in to two categories: less than (<) 6 months and greater than (>) 6 months.

Lack of efficacy was determined as per physicians' discretion. Intolerance was defined as the participant could not be treated due to safety reason (adverse events).

Only those participants that had dose modifications were reported.

TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

The safety variable measured the number of participants who discontinued TCZ due to adverse reactions to TCZ, and the efficacy variable measured the participants who discontinued from TCZ due to lack of efficacy according to criteria of the treating physician.

The number of participants who reported restoration of initial dosing regimen of TCZ for 84.00, 133.00, 158.00, 2.3.00 and 206.00 days, were reported.

A participant's adherence was calculated based on the adverse event or laboratory abnormality experienced by the participants who required dose modifications as per local TCZ label or protocol.

TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

Objective intolerance was determined by medical observation; subjective intolerance was determined by the participant; lack of efficacy was determined by physician discretion.

The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 28 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28.

The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 68 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 28 joints and were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28.

The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 66 joints and were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

DAS28 was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeter per hour [mm/hr]), and Participant's Global Assessment (PGH) of disease activity (measured on a 0 to 100 mm Visual Analogue Scale (VAS) where 0=no disease activity and 100=worst disease activity). DAS28 was calculated using following formula: DAS28 = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*PGH of disease activity. Total score range: 0-10, higher score=more disease activity. DAS28 <3.2 implied low disease activity, DAS >3.2 to 5.1 implied moderate disease activity and DAS >5.1 implied high disease activity, and DAS28 <2.6 = clinical remission.

Clinical response assessed as per EULAR categorical DAS28 response criteria was defined as clinically meaningful improvement at a particular time point. EULAR response was based on change from baseline (CFB) in the DAS28 score and also on the actual DAS28 score at the time point so was more reflective of the current status of the participant. The DAS28 score was a measure of the participant's disease activity, based on the TJC (28 joints), SJC (28 joints), PGH (mm), and ESR (mm/hr). DAS28 total scores ranged from 0 to approximately 10. Scores <2.6 = best disease control and scores >5.1 = worse disease control. A negative CFB indicated clinically meaningful improvement. EULAR Good response: DAS28 <=3.2 and a CFB <-1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a CFB < -0.6 to ≥ -1.2. EULAR No response: DAS28 ≤3.2 or CFB greater than or equal to (>=) -0.6, DAS28 >3.2 to <=5.1 or CFB >=-0.6 and DAS28 >5.1 or CFB >=-0.6.

The SDAI was a combined index for measuring disease activity in RA which reflected the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and physician's global assessment (PhGH) of disease activity, assessed on 0-100 mm VAS where 0 = no disease activity and 100 = worst disease activity, and C-reactive protein (CRP) (milligrams per deciliter [mg/dL]). SDAI total score = 0-86. A SDAI score of <=3.3 represented clinical remission, a score of >3.4 to <=11.0 represented low disease activity, a score of >11 to <=26.0 represented moderate disease activity and a score of >26.0 represented high (or severe) disease.

The CDAI was a combined index for measuring disease activity in RA and used to evaluate disease activity in the absence of laboratory testing of CRP and ESR. It was the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and PhGH (assessed on 0-100 mm VAS); VAS (0 = no disease activity and 100 = worst disease activity). CDAI total score = 0-76. A CDAI score of <=2.8 represented clinical remission, a score of >2.8 to <=10.0 represented low disease activity, a score of >10.0 to <=22.0 represented moderate disease activity and a score of >22.0 represented high (or severe) disease.

ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: participant's global assessment of pain, PGH, 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.

ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR50 response required at least a 50% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: (participant's global assessment of pain, PGH, 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), and acute phase reactant (CRP or ESR). A reduction in the level of acute phase reactants was considered an improvement.

ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR70 response required at least a 70% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: (participant's global assessment of pain, PGH, 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), and acute phase reactant (CRP or ESR). A reduction in the level of acute phase reactants was considered an improvement.

ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR90 response required at least a 90% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: (participant's global assessment of pain, PGH, 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), and acute phase reactant (CRP or ESR). A reduction in the level of acute phase reactants was considered an improvement.

The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

The Participant's Global Assessment of Disease Activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

The HAQ-DI was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ-DI scale was an average of all the scores and ranged from 0 to 3, where higher scores represented higher disease activity.

Fatigue was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the level of fatigue that they have experienced, ranging from 0 (no fatigue) to 100 (extreme fatigue).

Severity of pain was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the severity of pain that they had experienced because of their RA, ranging from 0 (no pain) to 100 (unbearable pain).

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.