An Observational Study of MabThera/Rituxan (Rituximab) in Patients With Rheumatoid Arthritis and an Inadequate Response or Intolerance to One Anti-Tumor Necrosis Factor (Anti-TNF) Agent

NCT01641952 | Completed Results

• 1 other identifier: ML27953
• Study Type: observational
• Target: 505
• Locations: 1 country
• Sites: 1

Brief Summary

This observational, prospective, multicenter study will evaluate the efficacy and safety of MabThera/Rituxan in participants with active rheumatoid arthritis and an inadequate response or intolerance to one anti-TNF therapy. Participants who receive MabThera/Rituxan according to the current standard and in line with the summary of product characteristics at a dose of 1000 milligram (mg) intravenously on Days 1 and 15 will be followed for 20 weeks.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (9)

• Percentage of Participant With Good or Moderate Response According to European League Against Rheumatism (EULAR) Response Criteria

  The DAS28 score is a measure of the participant's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\], and ESR. DAS28 total scores range from 0 to 10. DAS28 \<=3.2 indicates low disease activity, DAS28 \>3.2 to 5.1 indicates moderate to high disease activity. A negative change from Baseline indicates improvement. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline (CFB) and the level of disease activity reached. Good response: DAS28 \<=3.2 and a CFB \>1.2. Moderate response: DAS28 \<=3.2 and CFB \>0.6 to \<=1.2, DAS28 \>3.2 to \<=5.1 and CFB \>1.2 or \>0.6 to \<=1.2, DAS28 \>5.1 and CFB \>1.2. No response: DAS28 \<=3.2 and CFB \>=0.6, DAS28 \>3.2 to \<=5.1 and CFB \<=0.6, DAS28 \>5.1 and CFB \>0.6 to \<=1.2 or \<=0.6.

  Week 20

• Change From Baseline in DAS28-ESR at Week 20

  DAS28 was calculated from SJC and TJC using an assessment of 28 joints, the erythrocyte sedimentation rate (ESR) (milliliter per hour \[ml/hr\]), and Patient's Global Assessment (PGH) of disease activity \[measured on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0=no disease activity and 100=worst disease activity\]. DAS28 was calculated using the 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, with a higher score indicated 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.

  Baseline and Week 20

• Mean DAS28-ESR Score at Visit 4 (Week 20)

  DAS28 was calculated from SJC and TJC using an assessment of 28 joints, the erythrocyte sedimentation rate (ESR) (milliliter per hour \[ml/hr\]), and Patient'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 the 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, with a higher score indicated 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.

  Week 20

• Percentage of Participants With Change in DAS28-ESR of Greater Than or Equal (>=) 1.2 After First Course of Treatment

  DAS28 was calculated from SJC and TJC using an assessment of 28 joints, the erythrocyte sedimentation rate (ESR) (milliliter per hour \[ml/hr\]), and Patient'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 the 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, with a higher score indicated 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.

  Week 20

• Percentage of Participants With EULAR Response

  The DAS28 score is a measure of the participant's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\], and ESR. DAS28 total scores range from 0 to 10. DAS28 \<=3.2 indicates low disease activity, DAS28 \>3.2 to 5.1 indicates moderate to high disease activity. A negative CFB indicates improvement. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of CFB and the level of disease activity reached. Good response: DAS28 \<=3.2 and a CFB \>1.2. Moderate response: DAS28 \<=3.2 and CFB \>0.6 to \<=1.2, DAS28 \>3.2 to \<=5.1 and CFB \>1.2 or \>0.6 to \<=1.2, DAS28 \>5.1 and CFB \>1.2. No response: DAS28 \<=3.2 and CFB \>=0.6, DAS28 \>3.2 to \<=5.1 and CFB \<=0.6, DAS28 \>5.1 and CFB \>0.6 to \<=1.2 or \<=0.6.

  Week 20

• Percentage of Participants With EULAR Response in Subgroup of Participants Who Had Been Treated With Anti-TNF Previously

  The DAS28 score is a measure of the participant's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\], and ESR. DAS28 total scores range from 0 to 10. DAS28 \<=3.2 indicates low disease activity, DAS28 \>3.2 to 5.1 indicates moderate to high disease activity. A negative CFB indicates improvement. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of CFB and the level of disease activity reached. Good response: DAS28 \<=3.2 and a CFB \>1.2. Moderate response: DAS28 \<=3.2 and CFB \>0.6 to \<=1.2, DAS28 \>3.2 to \<=5.1 and CFB \>1.2 or \>0.6 to \<=1.2, DAS28 \>5.1 and CFB \>1.2. No response: DAS28 \<=3.2 and CFB \>=0.6, DAS28 \>3.2 to \<=5.1 and CFB \<=0.6, DAS28 \>5.1 and CFB \>0.6 to \<=1.2 or \<=0.6.

  Week 20

• Percentage of Participants With Remission (DAS28 <2.6) and Low Disease Activity Following Each Treatment Course

  DAS28 was calculated from SJC and TJC using an assessment of 28 joints, the erythrocyte sedimentation rate (ESR) (milliliter per hour \[ml/hr\]), and Patient'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 the 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, with a higher score indicated 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.

  Week 20

• Number of Participants With Remission (DAS28 <2.6) and Low Disease Activity Following Each Treatment Course for Subgroup of Participants Who Had Been Treated With Etanercept or Adalimumab or Infliximab Before Rituximab

  The DAS28 score is a measure of the participant's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\], and ESR. DAS28 total scores range from 0 to 10. DAS28 \<=3.2 indicates low disease activity, DAS28 \>3.2 to 5.1 indicates moderate to high disease activity. A negative change from Baseline (CFB) indicates improvement. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of CFB and the level of disease activity reached. Good response: DAS28 \<=3.2 and a CFB \>1.2. Moderate response: DAS28 \<=3.2 and CFB \>0.6 to \<=1.2, DAS28 \>3.2 to \<=5.1 and CFB \>1.2 or \>0.6 to \<=1.2, DAS28 \>5.1 and CFB \>1.2. No response: DAS28 \<=3.2 and CFB \>=0.6, DAS28 \>3.2 to \<=5.1 and CFB \<=0.6, DAS28 \>5.1 and CFB \>0.6 to \<=1.2 or \<=0.6.

  Week 20

• Number of Participants With Adverse Events (AE)

  An AE was defined as 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.

  Up to 39 months

Secondary Outcomes (1)

• Health Assessment Questionnaire (HAQ) Score at Week 20

  Baseline and Week 20

Study Arms (1)

Rituximab

Participants who had an inadequate response or intolerance to one anti- tumor necrosis factor (anti-TNF) agent received rituximab (Mabthera) at a dose determined by the investigator, guided by the recommendation in the Summary of Product Characteristics.

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab at a dose determined by the investigator, guided by the recommendation in the Summary of Product Characteristics.

Also known as: Mabthera

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants with active rheumatoid arthritis and an inadequate response or intolerant to one prior anti-TFN therapy initiated on treatment with MabThera/Rituxan

You may qualify if:

• Adult participants, \>/= 18 years of age
• Participants with rheumatoid arthritis, eligible for treatment with MabThera/Rituxan in accordance with summary of product characteristics (SPC)
• Inadequate response to a single TNF inhibitor defined as change in disease activity score-28 erythrocyte sedimentation rate (DAS28-ESR) \<1.2 or DAS28-ESR \>3.5 at 5 months after first course of anti-TNF therapy
• Participants with a clinical and biological evaluation performed within 12 weeks prior to enrollment may be included

You may not qualify if:

• More than one previous anti-TNF therapies
• Any other biological therapy apart from the one anti-TNF therapy
• Hypersensitivity to rituximab or any of the excipients or to murine proteins
• Active severe infections
• Participants in a severely immunocompromised state
• Severe heart failure \[New York Heart Association (NYHA) Class IV\] or severe, uncontrolled cardiac disease
• Women of childbearing potential not willing to use contraception
• Pregnant or breastfeeding women
• Participation in another trial

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

Bucharest, 020983, Romania

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: July 17, 2012
• Study Start: October 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: August 17, 2016
• Results First Posted: August 17, 2016

Record last verified: 2016-07

Locations

RO (1)