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Observational Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Clalit Health Services
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01579006
First received: April 16, 2012
Last updated: February 4, 2016
Last verified: February 2016
  Purpose
This multi-center, observational study will evaluate the clinical practice patterns, efficacy and safety of RoActemra/Actemra in patients with rheumatoid arthritis who have had an inadequate response (or were intolerant to) treatment with non-biological DMARDs or with one biological agent. Data will be collected from each eligible patient initiated on RoActemra/Actemra treatment by their treating physician according to approved label for 6 months from start of treatment.

Condition Intervention
Rheumatoid Arthritis
Drug: Tocilizumab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multi National, Multi-center Non-interventional Study in Rheumatoid Arthritis (RA) Patients Treated With Tocilizumab (Actemra)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants on TCZ Treatment at 6 Months After Treatment Initiation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Percentage of Participants on TCZ Treatment at 5-6 Months After Treatment Initiation [ Time Frame: 5-6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With Systemic Manifestations of RA at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Systemic manifestations included fibromyalgia, osteoporosis, sjogren's syndrome, anemia, rheumatoid nodules, pulmonary fibrosis, vasculitis, peripheral neuropathy or mononeuropathy, scleritis, episcleritis, hypertension, hyperlipidemia, low high-density lipoproteins, diabetes type 1 and type 2, metabolic syndrome, carotid artery disease, transient ischemic attacks, embolic stroke, atherothrombotic stroke, atrial fibrillation, heart failure New York Heart Association (NYHA) Class l/ll, coronary heart disease(angina pectoris/myocardial), aortic aneurism, peripheral arterial occlusive disease, percutaneous coronary interventions, coronary artery bypass, carotid endarterectomy and peripheral arterial bypass.

  • Percentage of Participants Who Received DMARDs Prior to Start of Study and Concomitantly With TCZ During the Study [ Time Frame: Prior to study start (8 weeks) and Baseline up to 6 months ] [ Designated as safety issue: No ]
    DMARDs exposure was evaluated for all participants. "Prior DMARDs treatment" included participants, who were treated with DMARDs 8 weeks and according to physician's discretion before being included in the study. "DMARDs treatment at baseline" included participants who were receiving DMARDs when they were included in the study and continued with this concomitant medication in addition to TCZ. Only those participants who received DMARDs prior to start of study and at Baseline up to 6 months were reported.

  • Percentage of Participants With Reason for DMARD Withdrawal [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Objective intolerance was determined by medical observation; subjective intolerance was determined by the participant; lack of efficacy was determined by physician discretion.

  • Percentage of Participants Who Received Biological RA Treatment Prior to Start of Study [ Time Frame: Prior to study start (8 weeks) ] [ Designated as safety issue: No ]
    Biological RA treatment exposure was evaluated for all participants. "Prior biological RA treatment" included participants who were treated with biological RA treatment 8 weeks before being included in the study. Percentage of participants who did not receive any biological RA treatment and percentage of participants who received one or more biologic RA treatments were reported.

  • Percentage of Participants With Type of Previous Biologic RA Treatments [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Previous biologic RA treatment included adalimumab, infliximab, golimumab, etanercept, certolizumab, and other (any other previous biologic RA treatment). Same participants may be counted in more than one previous biologic RA treatment category.

  • Duration of Previous Biologic RA Treatments [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Previous biologic RA treatment included adalimumab, infliximab, golimumab, etanercept, certolizumab, and other (any other previous biologic RA treatment).

  • Percentage of Participants With Reasons for Termination of Previous Biologic RA Treatments [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Lack of efficacy was determined by physician discretion. Previous biologic RA treatment included adalimumab, infliximab, golimumab, etanercept, certolizumab, and other (any other previous biologic RA treatment).

  • Percentage of Participants With Dose Modifications [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

  • Percentage of Participants With Reasons for Dose Modification [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations. Only those participants who had dose modifications were reported.

  • Mean Dose at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

  • Mean Number of Dose Modifications at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

  • Mean Dosing Interval of Treatment at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations. The mean dosing interval between different TCZ administrations (Adm) by participants within 6 months observational period was presented.

  • Percentage of Participants Who Discontinued From TCZ for Safety Versus Efficacy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The safety variable measured the number of participants who discontinued TCZ due to adverse reactions to TCZ, and the efficacy variable measured the participants who discontinued from TCZ due to lack of efficacy according to criteria of the treating physician.

  • Time to Restoration of Initial Dosing Regimen [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Adhered to the Dosing Regimen Recommended by Physician [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A participant's adherence was calculated based on the adverse event or laboratory abnormality experienced by the participants who required dose modifications as per local TCZ label or protocol.

  • Percentage of Participants on TCZ Monotherapy [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations. Only those participants who had TCZ as monotherapy were reported.

  • Change From Baseline in Tender Joint Count (TJC) (68 Joints) at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The number of tender joints was recorded on the joint assessment form, with no tenderness = 0, and tenderness = 1, for 68 joints, giving a total possible TJC score of 0 to 68.

  • Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The number of swollen joints was recorded on the joint assessment form, with no swelling = 0, and swelling =1, for 66 joints, giving a total possible SJC score of 0 to 66.

  • Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    DAS28 was calculated from SJC and TJC using an assessment of 28 joints, the erythrocyte sedimentation rate (ESR) (milliliter per hour [mm/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.

  • Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Clinical response assessed as per EULAR categorical DAS28 response criteria was defined as clinically meaningful improvement at a particular time point. EULAR response was based on change from baseline (CFB) in the DAS28 score and also on the actual DAS28 score at the time point so was more reflective of the current status of the participant. The DAS28 score was a measure of the participant's disease activity, based on the TJC (28 joints), SJC (28 joints), PGH (mm), and ESR (mm/hr). DAS28 total scores ranged from 0 to approximately 10. Scores <2.6 = best disease control and scores >5.1 = worse disease control. A negative CFB indicated clinically meaningful improvement. EULAR Good response: DAS28 <=3.2 and a CFB <-1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a CFB < -0.6 to ≥ -1.2. EULAR No response: DAS28 ≤3.2 or CFB >=-0.6, DAS28 >3.2 to <=5.1 or CFB >=-0.6 and DAS28 >5.1 or CFB >=-0.6.

  • Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The SDAI was a combined index for measuring disease activity in RA which reflected the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and physician's global assessment (PhGH) of disease activity, assessed on 0-100 mm VAS where 0 = no disease activity and 100 = worst disease activity, and C-reactive protein (CRP) (milligrams per deciliter [mg/dL]). SDAI total score = 0-86. A SDAI score of <=3.3 represented clinical remission, a score of <=11.0 represents low disease activity, a score of <=26.0 represented moderate disease activity and a score of >26.0 represented high (or severe) disease.

  • Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The CDAI was a combined index for measuring disease activity in RA and used to evaluate disease activity in the absence of laboratory testing of CRP and ESR. It was the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and PhGH (assessed on 0-100 mm); VAS (0 = no disease activity and 100 = worst disease activity). CDAI total score = 0-76. A CDAI score of <=2.8 represented clinical remission, a score of <=10.0 represented low disease activity, a score of <=22.0 represented moderate disease activity and a score of >22.0 represented high (or severe) disease.

  • Percentage of Participants Who Achieved 20% Improvement in ACR (ACR20) Response at Month 6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: participant's global assessment of pain, PGH, 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.

  • Percentage of Participants Who Achieved 50% Improvement in ACR (ACR50) Response at Month 6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR50 response required at least a 50% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: (participant's global assessment of pain, PGH, 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), and acute phase reactant (CRP or ESR). A reduction in the level of acute phase reactants was considered an improvement.

  • Percentage of Participants Who Achieved 70% Improvement in ACR (ACR70) Response at Month 6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR70 response required at least a 70% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: (participant's global assessment of pain, PGH, 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), and acute phase reactant (CRP or ESR). A reduction in the level of acute phase reactants was considered an improvement.

  • Change From Baseline in CRP at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The test for CRP was a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. The serum concentration of CRP was measured in mg/dL. A reduction in the level was considered an improvement.

  • Change From Baseline in ESR at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    ESR was a laboratory test that provided a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube. ESR was measured in mm/hr. A reduction in the level was considered an improvement.

  • Change From Baseline in PhGH at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The PhGH was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement.

  • Change From Baseline in PGH of Disease Activity at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The PGH of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement.

  • Change From Baseline in HAQ-DI at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The HAQ-DI was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from "no difficulty" to "unable to do", corresponding to scores from 0 to 3. The HAQ-DI scale was an average of all the scores and ranged from 0 to 3, where higher scores represented higher disease activity. A score of <0.5 represented clinical remission. A participant achieved a clinically meaningful improvement in HAQ-DI if they had a reduction from baseline of >=0.22.

  • Change From Baseline in Participant's Assessment of Fatigue Using VAS at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Fatigue was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the level of fatigue that they have experienced, ranging from 0 (no fatigue) to 100 (extreme fatigue).

  • Change From Baseline in Participant's Assessment of RA-Related Pain at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Severity of pain was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the severity of pain that they had experienced because of their RA, ranging from 0 (no pain) to 100 (unbearable pain). A decrease of 10 points was considered clinically meaningful.

  • Change From Administration 1 in Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Questionnaire at Month 6 [ Time Frame: Administration 1 (Baseline), 6 months ] [ Designated as safety issue: No ]
    The FACIT Measurement System was a collection of health-related quality of life questionnaires targeted to the management of chronic illness and included questions on Physical Well-Being, Social/Family Well-Being, Emotional Well-Being and Functional Well-Being. The FACIT Fatigue Scale was a 13-item tool that measured an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a five-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score of FACIT ranged from 0 to 160. An increase of 4 points in the FACIT-Fatigue score was considered clinically meaningful. Change from Administration 1 was reported for individual administration schedules. TCZ was administered every 4 weeks according to the label. Due to the observational nature of the study, the suggested schedule was subject to changes according to physician and participant considerations.

  • Change From Baseline in Morning Stiffness as Assessed Using VAS at Month 6 [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 184
Study Start Date: May 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cohort Drug: Tocilizumab
Other Name: Actemra

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Rheumatoid arthritis patients treated with tocilizumab
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Moderate to severe rheumatoid arthritis
  • Inadequate response (or intolerant) to non-biological DMARDs or one biologic agent
  • Patients initiating treatment with RoActemra/Actemra on their physician's decision (in accordance with the local label), including patients who started treatment with RoActemra/Actemra in the 8 weeks prior to the enrolment visit

Exclusion Criteria:

  • RoActemra/Actemra treatment more than 8 weeks prior to the enrolment visit
  • Previous RoActemra/Actemra treatment in a clinical trial or for compassionate use
  • Enrolled in an ongoing clinical trial and/or treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever is longer) before starting treatment with RoActemra/Actemra
  • History of autoimmune disease or any joint inflammatory disease other than rheumatoid arthritis
  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: NCT01579006

Locations
Israel
Afula, Israel, 18101
Beer Sheva, Israel, 8410101
Beer Yaakov, Israel, 6093000
Hadera, Israel, 38100
Haifa, Israel, 31048
Haifa, Israel, 3109601
Haifa, Israel, 34362
Jerusalem, Israel, 9112001
Jerusalem, Israel, 91240
Kfar Saba, Israel, 44281
Petach Tikva, Israel, 4937211
Petach Tikva, Israel, 4941492
Ramat Gan, Israel, 5262000
Ramat-Gan, Israel, 52621
Sponsors and Collaborators
Hoffmann-La Roche
Clalit Health Services
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01579006     History of Changes
Other Study ID Numbers: ML28164 
Study First Received: April 16, 2012
Results First Received: December 8, 2015
Last Updated: February 4, 2016
Health Authority: Israel: Ministry of Health

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

ClinicalTrials.gov processed this record on September 26, 2016