An Observational Study of MabThera/Rituxan (Rituximab) in Patients With Sero-Positive Rheumatoid Arthritis Who Are Non-Responders or Intolerant to a Single TNF-Inhibitor (PORTSMAB)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01309282
First received: March 3, 2011
Last updated: March 29, 2016
Last verified: March 2016
  Purpose
This observational study will assess the long-term efficacy and safety of MabThera/Rituxan in routine clinical practice in patients with sero-positive rheumatoid arthritis who are non-responders or intolerant to a single tumour necrosis factor (TNF) inhibitor. Data will be collected from each patient over 2 years.

Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Portuguese Observational Re-Treatment Study of MabThera (PORTSMAB) - A Two-centre Observational Study in Sero-positive Rheumatoid Arthritis (RA) Patients Who Are Non-responders or Intolerant to a Single Tumor Necrosis Factor (TNF) Inhibitor

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Mean Change From Baseline in Disease-activity Score 28-Erythrocyte Sedimentation Rate at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The disease-activity score 28 (DAS28) score is a measure of validated instrument for the assessment of the overall severity of RA disease activity calculated using the tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity, and erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.


Secondary Outcome Measures:
  • Mean Change From Baseline in TJC at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in SJC at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/ not swollen (0) giving a total possible SJC score of 0 to 28. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in ESR at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in C-reactive Protein at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The C-reactive protein is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Physician's Global Assessment of Disease Activity At Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The Physician's Global Assessment of disease activity was assessed using a Visual Analogue Scale (VAS). 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).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  • Mean Change From Baseline in Patient's Global Assessment of Disease Activity at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The Patient's Global Assessment of disease activity was assessed using VAS. 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).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  • Mean Change From Baseline in Severity of Pain at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The patient's assessment of pain was performed using a 100 mm VAS ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.

  • Mean Change Form Baseline in Functional Capacity at Month 24 [ Time Frame: Baseline (Day 0) and Month 24 ] [ Designated as safety issue: No ]
    The functional capacity was analyzed using Health Assessment Questionnaire-Disability Index (HAQ-DI). It is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 domains (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each domain are scored from 0 to 3 (0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do). Overall score was computed as sum of domain scores and divided by the number of domains. A total possible score ranged from 0 (best) to 3 (worst).

  • Reason for Change From First TNF-inhibitor Therapy to Rituximab [ Time Frame: At Screening ] [ Designated as safety issue: No ]
    Adverse event, primary and secondary insufficient responses and monoclonal gammopathy were the reasons for starting rituximab therapy.

  • Number of Participants on Each Pattern of Re-treatment [ Time Frame: Up to Month 24 ] [ Designated as safety issue: No ]

    There are two patterns of re-treatment, namely treat-to-target and according to the clinic.

    Treat-to-target: a new cycle every 6 months if not in remission, with the participant receiving no new course of treatment as long as he is in remission.

    On demand (according to clinic): a new cycle when, in an assessment performed at least 16 weeks after the last treatment cycle, the participant shows moderate or high disease activity [DAS28 > 3.2 or difference in DAS28 (ΔDAS28) > 0.6]


  • Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions [ Time Frame: At Months 6, 12 and 24 ] [ Designated as safety issue: No ]
    An infusion reaction or injection site reaction is an event that occurs after infusion or injection which may include hypersensitivity reactions or anaphylactic reactions.

  • Number of Participants With Incidence of Infectious Events [ Time Frame: At Months 6, 12 and 24 ] [ Designated as safety issue: No ]
    Follow-up of the infectious events was done after Month 6 visit, Month 12 visit and Month 24 visit.

  • Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events [ Time Frame: Up to Month 24 ] [ Designated as safety issue: No ]
    An Adverse Events (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect


Enrollment: 9
Study Start Date: July 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Rituximab
Sero-positive [Rheumatoid Factor (RF) and/or anti-Cyclic Citrullinated Peptide (CCP+)] rheumatoid arthritis (RA) patients, who had initiated therapy with Rituximab (MabThera) following lack of response or intolerance to a single tumour necrosis factor (TNF)-inhibitor will be included in this arm

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with sero-positive rheumatoid arthritis starting treatment with MabThera/Rituxan following lack of response or intolerance to single TNF-inhibitor
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Rheumatoid arthritis positive for rheumatoid factor and/or anti-CCP
  • Non-responder or intolerant to single TNF-inhibitor therapy
  • Initiating treatment with MabThera/Rituxan

Exclusion Criteria:

  • Contra-indications to MabThera/Rituxan therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309282

Locations
Portugal
Lisboa, Portugal, 1649-035
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01309282     History of Changes
Other Study ID Numbers: ML22935 
Study First Received: March 3, 2011
Results First Received: February 12, 2016
Last Updated: March 29, 2016
Health Authority: Portugal: Instituto Nacional da Farmácia e do Medicamento INFARMED

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on May 04, 2016