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A Non-Interventional Study of RoActemra/Actemra in Patients With Moderate to Severe Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01672970
First received: August 22, 2012
Last updated: February 29, 2016
Last verified: February 2016
  Purpose
This multi-center observational study will evaluate the use of RoActemra/Actemra (tocilizumab) in patients with rheumatoid arthritis. Eligible patients initiated on RoActemra/Actemra treatment according to the local label will be followed for 6 months.

Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Multicenter, Post-marketing, Non-interventional, Observational Study in RA Patients Treated With Tocilizumab.

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 ]

Secondary Outcome Measures:
  • Percentage of Participants With Systemic Manifestations of RA at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Systemic manifestations of RA at baseline included anemia, fatigue, conventional risk factor(s) for cardiovascular disease, C-reactive protein (CRP) above upper limit of normal rheumatoid nodules, rheumatoid vasculitis, and interstitial lung disease.

  • Percentage of Participants Who Stopped DMARDs Prior to Start of Study and at Baseline [ Time Frame: Prior to study (8 weeks) to Baseline ] [ Designated as safety issue: No ]
    DMARDs exposure was evaluated for all participants. "Prior DMARDs treatment" included participants, who were treated with DMARDs 8 weeks 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.

  • Percentage of Participants With Reason for DMARDs Withdrawal at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    DMARDs exposure was evaluated for all participants. DMARDs treatment at baseline included participants, who were receiving DMARDs when they were included in the study and discontinued at baseline and not used as concomitant medication to TCZ.

  • Number of Previous Biologic RA Treatments Received by Participants [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Percentage of Participants With Duration of Previous Biologic RA Treatments [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The duration of previous biologic RA treatments was classified in to two categories: less than (<) 6 months and greater than (>) 6 months.

  • Percentage of Participants With Reasons for Termination of Previous Biologic RA Treatments [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Lack of efficacy was determined as per physicians' discretion. Intolerance was defined as the participant could not be treated due to safety reason (adverse events).

  • Number of Participants With Reasons for Dose Modification for TCZ [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Only those participants that had dose modifications were reported.

  • Mean Dose of TCZ 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.

  • Percentage of Participants Discontinued From Tocilizumab for Safety And Efficacy Reasons [ 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.

  • Number of Participants With Restoration of Initial Dosing Regimen of TCZ [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The number of participants who reported restoration of initial dosing regimen of TCZ for 84.00, 133.00, 158.00, 2.3.00 and 206.00 days, were reported.

  • Percentage of Participants Adhered to the Dosing Regimen Recommended by Physician for TCZ [ 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 Tocilizumab Monotherapy [ 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 Reason for DMARD Withdrawal [ Time Frame: 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.

  • Change From Baseline in Tender Joint Count (28 Joints) at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 28 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28.

  • Change From Baseline in Tender Joint Count (68 Joints) at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 68 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

  • Change From Baseline in Swollen Joint Count (28 Joints) at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 28 joints and were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28.

  • Change From Baseline in Swollen Joint Count (66 Joints) at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 66 joints and were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

  • Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    DAS28 was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeter per hour [mm/hr]), and Participant'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 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, higher score=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 [ Time Frame: Visit 2 (Month 1), Visit 3 (Month 2), Visit 4 (Month 3), Visit 5 (Month 4), Visit 6 (Month 5), Visit 7 (Months 6) and Visit 8 (Final Visit; within 2 weeks after 6months observation period) ] [ 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 greater than or equal to (>=) -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 Months 3 and 6 [ Time Frame: Baseline, 3 and 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 >3.4 to <=11.0 represented low disease activity, a score of >11 to <=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 Months 3 and 6 [ Time Frame: Baseline, 3 and 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); 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 >2.8 to <=10.0 represented low disease activity, a score of >10.0 to <=22.0 represented moderate disease activity and a score of >22.0 represented high (or severe) disease.

  • Percentage of Participants Who Achieved 20 Percent (%) Improvement in ACR (ACR20) Response [ Time Frame: Baseline, 3 and 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 [ Time Frame: Baseline, 3 and 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 [ Time Frame: Baseline, 3 and 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.

  • Percentage of Participants Who Achieved 90% Improvement in ACR (ACR90) Response [ Time Frame: Baseline, 3 and 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 ACR90 response required at least a 90% 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 Physician Global Assessment of Disease Activity at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was assessed using 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, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Participant Global Assessment of Disease Activity at Months 3 and 6 [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    The Participant's Global Assessment of Disease Activity was assessed using 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, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Months 3 and 6 [ Time Frame: Baseline, 3 and 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 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ-DI scale was an average of all the scores and ranged from 0 to 3, where higher scores represented higher disease activity.

  • Change From Baseline in Participant's Assessment of Fatigue Using VAS at Months 3 and 6 [ Time Frame: Baseline, 3 and 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 Using VAS at Months 3 and 6 [ Time Frame: Baseline, 3 and 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).

  • Change From Baseline in Particpant's Assessment of RA Morning Stiffness Assessed Using VAS at Months 3 and 6 [ Time Frame: Baseline, 3 and 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: 291
Study Start Date: July 2012
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Moderate to severe rheumatoid arthritis according to the revised (1987) ACR criteria
  • Patients in whom the treating physician has made the decision to commence RoActemra/Actemra treatment (in accordance with the local label); this can include patients who have received RoActemra/Actemra treatment within 8 week prior to the enrolment visit

Exclusion Criteria:

  • Patients who have received RoActemra/Actemra more than 8 weeks prior to the enrolment visit
  • Patients who have previously received RoActemra/Actemra 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 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: NCT01672970

Locations
Hungary
Budapest, Hungary, 1023
Budapest, Hungary, 1027
Budapest, Hungary, 1062
Debrecen, Hungary, 4032
Debrecen, Hungary, 4043
Eger, Hungary, 3300
Esztergom, Hungary, 2500
Gyor, Hungary, 9004
Gyula, Hungary, 5700
Heviz, Hungary, 8380
Kecskemet, Hungary, 6000
Kistarcsa, Hungary, 2143
Miskolc, Hungary, 3529
Nyiregyhaza, Hungary, 4400
Pécs, Hungary, 7632
Szeged, Hungary, 6724
Szekesfehervar, Hungary, 8000
Szolnok, Hungary, 5000
Szombathely, Hungary, 9700
Veszprem, Hungary, 8200
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01672970     History of Changes
Other Study ID Numbers: ML28212 
Study First Received: August 22, 2012
Results First Received: January 28, 2016
Last Updated: February 29, 2016
Health Authority: Hungary: National Institute of Pharmacy

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

ClinicalTrials.gov processed this record on September 30, 2016