A Non-Interventional Study Evaluating Rheumatoid Arthritis Participants Treated With Tocilizumab (RoActemra/Actemra)

A Multi-Center, Non-Interventional Study to Evaluate Rheumatoid Arthritis (RA) Patients Treated With Tocilizumab (ACROSS)

This non-interventional study evaluated the use and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis. Eligible participants initiated on tocilizumab treatment according to the approved label were followed for 6 months.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Serbia
  • Belgrade, Serbia, 11000
  • Belgrade, Serbia, 11000
    • Military Medical Academy; Clinic of Rheumatology
  • Belgrade, Serbia, 11000
    • Institut Za Reumatologiju; Reumatologiju
  • Niska Banja, Serbia, 18205
  • Niska Banja, Serbia, 18205
    • Institute of Rheumatology and Cardiovascular Diseases; Rheumatology
  • Novi Sad, Serbia, 21000
  • Novi Sad, Serbia, 21000
    • Special Hospital for Rheumatic Diseases Novi Sad
  • Novi Sad, Serbia, 21000
    • Clinical Center Voivodina; Clinic for Immunology and Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants with rheumatoid arthritis initiated on treatment with tocilizumab (RoActemra/Actemra)

Description

Inclusion Criteria:

• Adult participants, >/= 18 years of age
• Moderate to severe rheumatoid arthritis according to the revised (1987) American College of Rheumatology (ACR) criteria
• Participants in whom the treating physician made the decision to commence tocilizumab treatment (in accordance with the local label); this could include participants who had received tocilizumab treatment within 8 weeks prior to the enrollment visit

Exclusion Criteria:

• Participants who had received tocilizumab more than 8 weeks prior to the enrollment visit
• Participants who had previously received tocilizumab in a clinical trial or for compassionate use
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever was longer) before starting treatment with tocilizumab
• History of autoimmune disease or any joint inflammatory disease other than rheumatoid arthritis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Tocilizumab; Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants on Tocilizumab 6 Months After Treatment Initiation	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Dose Modifications		6 months
Percentage of Participants Receiving Tocilizumab After Failing Disease-Modifying Anti-Rheumatic Drugs (DMARDs)		6 months
Percentage of Participants Receiving Tocilizumab After Failing Other Biologic Agents		Baseline
Reasons for Dose Modifications		6 months
Percentage of Participants With Dose Interruptions		6 months
Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy		6 months
Percentage of Participants on Tocilizumab Monotherapy at Study Entry		6 months
Disease Activity Score Based on 28-Joint Count (DAS28)	DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.	6 months
Percentage of Participants on Combination Therapy Achieving a Response by European League Against Rheumatism (EULAR) Category	Percentage of participants achieving a response by EULAR category, including moderate, good, or no response. 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 and the level of disease activity reached. Good response: change from baseline <-1.2 with a DAS28 score ≤3.2; Moderate response: change from baseline <-1.2 with DAS28 scores >3.2 to ≤ 5.1 or >5.1, or a change from baseline <-0.6 to ≥-1.2 with DAS28 scores ≤3.2 and >3.2 to ≤5.1; No response: change from baseline <-0.6 to ≥-1.2 with DAS28 score >5.1, or a change from baseline ≥-0.6 with DAS28 scores ≤3.2, >3.2 to ≤ 5.1, or >5.1.	6 months
Percentage of Participants on Monotherapy Achieving a Response by European League Against Rheumatism (EULAR) Category	Percentage of participants achieving a response by EULAR category, including moderate, good, or no response. 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 and the level of disease activity reached. Good response: change from baseline <-1.2 with a DAS28 score ≤3.2; Moderate response: change from baseline <-1.2 with DAS28 scores >3.2 to ≤ 5.1 or >5.1, or a change from baseline <-0.6 to ≥-1.2 with DAS28 scores ≤3.2 and >3.2 to ≤5.1; No response: change from baseline <-0.6 to ≥-1.2 with DAS28 score >5.1, or a change from baseline ≥-0.6 with DAS28 scores ≤3.2, >3.2 to ≤ 5.1, or >5.1.	6 months
Simplified Disease Activity Index (SDAI)	Simplified Disease Activity Index (SDAI) is an index for measuring disease activity in RA and has a good correlation with the DAS28. The index is calculated using the following formula: SDAI: swollen joint count (SJC28) + tender joint count (TJC28) + physician global assessment (PGA) (10 cm visual analogue scale [VAS]) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligrams/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores range from 0 to 86, with higher scores also indicating increased disease activity.	6 months
Clinical Disease Activity Index (CDAI) Score	Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in RA. The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity.	6 months
Percentage of Participants With American College of Rheumatology (ACR) Response	ACR response was calculated based on total joint count evaluation and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (28 joints) and tender joint count (28 joints) and at least 3 of the following 5 assessments: patient's global assessment of pain, participant's global assessment of disease activity (PGH), physician's global assessment of disease activity (PhGH) (all 3 assessed at 0 [good] to 100 mm [worst] VAS scale); participant assessment of disability measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessed on a 0 to 3 scale, where higher scores represented higher disease activity); acute phase reactant (CRP or ESR). A reduction in the level of and acute phase reactants was considered an improvement. ACR50 and ACR70 require a 50% and 70% improvement from baseline, respectively.	6 months
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs)	An AESI includes serious/medically significant infections; opportunistic infections; cases of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), in combination with either elevated bilirubin or clinical jaundice; suspected transmission of an infectious agent by the study drug; myocardial infarction /acute coronary syndrome; gastrointestinal perforations; malignancies; anaphylaxis / hypersensitivity reactions (including injection site reactions); demyelinating disorders; stroke; serious/medically significant bleeding events; or serious/medically significant hepatic events.	6 months
Patient Global Assessment of Disease Activity Score	The Patient Global Assessment of disease activity provides an overall assessment of how RA affects the participant using a visual analogue score, where 0 indicates they are managing very well and 100 indicates they are managing very poorly. A decrease in the score indicates improvement.	6 months
Health Assessment Questionnaire Disability Index (HAQ-DI)	The HAQ is a participant self-reported questionnaire for assessing the extent of the participant's functional ability. It consists of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question has 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ scale is an average of all the scores and ranges from 0 to 3, where higher scores represent higher disease activity.	6 months
Visual Analogue Scale (VAS) for Fatigue	The VAS-fatigue provides an overall assessment of the level of fatigue that the participant is experiencing using a visual analogue score, where 0 indicates no fatigue, and 100 indicates extreme fatigue. A decrease in the score indicates improvement.	6 months
Visual Analogue Scale (VAS) for Morning Stiffness	Morning stiffness was defined by the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was as limber as he/she would be during a day involving typical activities. Morning stiffness was assessed on a 100 mm VAS, where 0= none and 100= very severe.	6 months
Visual Analogue Scale (VAS) for Pain	The VAS-Pain provides an overall assessment of the severity of pain that the participant is experiencing using a visual analogue score, where 0 indicates no pain and 100 indicates unbearable pain. A decrease in the score indicates improvement.	6 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (Estimate): August 23, 2012

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 6, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML28314