Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Participants With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Non-Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) and/or Anti-tumor Necrosis Factor (Anti-TNF) Therapy

N/ACompletedNCT01362062

Hoffmann-La Roche110 enrolled

Overview

This observational study will evaluate the safety, tolerability and efficacy of tocilizumab in participants with moderate to severe RA who have an inadequate response to current non-biologic DMARD and/or anti-TNF therapy. Data will be collected from each participant during tocilizumab therapy and on follow-up for a total of 12 months.

Study Type

OBSERVATIONAL

Enrollment

110

Conditions

Rheumatoid Arthritis

Interventions

TocilizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Moderate to severe active RA with an inadequate response to existing therapies (DMARDs and/or anti-TNFs) * Considered eligible for tocilizumab therapy by the treating physician as per routine clinical practice Exclusion Criteria: * Pregnant or breastfeeding females * Immunization with live/attenuated vaccine within 4 weeks prior to baseline * Participants with clinically significant raised liver enzyme, abnormal lipid profile, platelet count, hemoglobin, white blood cell and neutrophil count * History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies * Participants with active tuberculosis (TB). Participants with latent TB should be treated with standard anti-mycobacterial therapy before initiating tocilizumab and have a negative chest x ray for active TB at enrolment * History of diverticulitis, chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations then the benefit risk ratio should be considered by treating physician * Know active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infection * History of or currently active primary or secondary immunodeficiency or known human immunodeficiency virus (HIV) positive status * Any other condition which puts the participant to undue risk for tocilizumab therapy as per local prescribing information or Investigator's judgement

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal product. An AE is considered as an SAE if it fulfills one of the following criteria: a) fatal or life-threatening, b) requires in-patient hospitalization or prolongation of existing hospitalization, c) results in a persistent or significant disability, d) results in a congenital abnormality/birth defect, e) is medically significant. AEs included serious as well as non-serious AEs.

Time frame: Up to 12 months

Secondary Outcomes

Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit

DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, erythrocyte sedimentation rate (ESR) (in millimeters \[mm\]/hour), and the participant's global assessment of disease activity (100 mm visual analog scale \[VAS\]: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*square root (√) of TJC + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement.

Time frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)

Time Required to Achieve Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units)

DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement. Time taken to achieve clinically meaningful improvement in DAS28 was reported.

Time frame: Up to 12 months

Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit

DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low Disease Activity is defined as DAS28 value of \<3.2 Units at the time of assessment.

Time Required to Achieve Low Disease Activity (DAS28 <3.2 Units)

DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low disease activity is defined as decrease in DAS28 to a value \<3.2 Units at the time of assessment. Time taken to achieve low disease activity was reported.

Time frame: Up to 12 months

Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit

Time Taken to Achieve Remission (DAS28 <2.6 Units)

DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). Remission is defined as DAS28 value of \<2.6 units at the time of assessment. Time taken to achieve remission is reported.

Time frame: Up to 12 months

Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit

ACR20/ACR50/ACR70/ACR 90 response: greater than or equal to (≥) 20%/50%/70%/90% improvement in tender and swollen joint counts and 20%/50%/70%/90% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) Participant assessment of disease activity, 3) Participant assessment of pain (VAS), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) ESR at each visit.

Change From Baseline (CFB) in ESR Values at Every Visit

Time frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)

Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit

Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit

The participant's global assessment of disease activity is assessed on 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, and is described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement.

Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit

The physician's global assessment of disease activity is assessed on 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, and is described as "maximum disease activity" (maximum arthritis disease activity).

Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit

The participant assessed their pain on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm, and is described as "unbearable pain". A negative change indicated improvement.

Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit

HAQ-DI is a self-completed patient questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The HAQ-DI is the sum of the scores from all domains and ranged from 0 (best) to 24 (worst). A negative change from baseline indicated improvement.

Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Participants With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Non-Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) and/or Anti-tumor Necrosis Factor (Anti-TNF) Therapy

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes