This single arm study will assess the safety of MabThera plus methotrexate in patients with rheumatoid arthritis who have had a lack of response to 1-5 DMARDs or biological agents. Patients will receive MabThera (1g i.v.) on days 1 and 15, concomitantly with methotrexate \>=15mg p.o./week. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
246
\>=15 mg po/week
1g iv on days 1 and 15
Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death
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.
Time frame: Up to Week 48
Number of Participants With AEs According to Degree of Intensity
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).
Time frame: Up to Week 48
Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and 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.
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Unnamed facility
Buenos Aires, Argentina
Unnamed facility
Buenos Aires, Argentina
Unnamed facility
Buenos Aires, Argentina
Unnamed facility
Córdoba, Argentina
Unnamed facility
San Miguel de Tucumán, Argentina
Unnamed facility
Belém, Brazil
Unnamed facility
Brasília, Brazil
Unnamed facility
Brasília, Brazil
Unnamed facility
Campinas, Brazil
Unnamed facility
Campinas, Brazil
...and 39 more locations
Time frame: Up to Week 48
Number of Participants With AEs of Special Interest During the Study
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.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration)
The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils)
The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume)
Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes)
The mean erythrocyte concentration for each participant was estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets)
The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose)
The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and 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.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit
The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit
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.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Mean Duration of Morning Joint Stiffness
The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness.
Time frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Mean Value of Painful Joints
The efficacy of rituximab was assessed by evaluating painful joints.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria
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.
Time frame: Week 1, Week 12, and Week 24
Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index)
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).
Time frame: Screening (Days -28 to 0), Week 1, Week 12, and Week 24
Mean Values of C Reactive Protein
C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation.
Time frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Mean Values of Globular Sedimentation Velocity
Globular sedimentation velocity is a component of ACR.
Time frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24
Mean Values of Pain and Activity Based on Visual Analogue Scale
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).
Time frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24
Mean Value of Inflamed Joints
The efficacy of rituximab was assessed by evaluating inflamed joints.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)