A Non-Comparative Study to Assess the Safety of MabThera (Rituximab) in Patients With Rheumatoid Arthritis.

An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment.

An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs).

An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification "Yes" and "No". A relationship classified as "Yes" implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments.

Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit.

The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit.

The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT.

Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT.

The mean erythrocyte concentration for each participant was estimated at Screening and at EOT.

The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit.

The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit.

The mean concentration of cholesterol, uric acid, urea, creatinine, calcium, total bilirubin and serum total proteins (STP) for each participant was estimated at Screening and at EOT visit.

The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT.

The mean aspartate transaminase (AST) and alanine transaminase (ALT), Alkaline phosphatase (AP), and Lactic dehydrogenase (LDH) concentration for each participant was estimated at Screening and at EOT visit.

The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness.

The efficacy of rituximab was assessed by evaluating painful joints.

American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender joints and swollen joints, as well as for three of the additional five ACR core set variables: patient's assessment of pain using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain); patient's global assessment of disease activity and physician's global assessment of disease activity using a VAS (0=no disease activity to 100=maximum disease activity); health assessment questionnaire (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant; C-reactive protein and globular sedimentation velocity.

Health Assessment Questionnaire - Disease Index (HAQ-DI) indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all).

C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation.

Globular sedimentation velocity is a component of ACR.

Pain assessment was assessed by using a VAS (0=no pain to 100=unbearable pain). Disease activity was also evaluated by participants and investigators by using a VAS (0=no disease activity to 100=maximum disease activity).

The efficacy of rituximab was assessed by evaluating inflamed joints.