Trial Outcomes & Findings for A Non-Interventional Study of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis (NCT NCT01670045)

NCT ID: NCT01670045

Last Updated: 2016-10-24

Results Overview

• Recruitment status: COMPLETED
• Target enrollment: 43 participants
• Primary outcome timeframe: Month 6
• Results posted on: 2016-10-24

Participant Flow

Participant milestones

Measure	Rheumatoid Arthritis Participants Participants with moderate to severe rheumatoid arthritis (RA) according to the American College of Rheumatology (ACR) criteria and the Disease Activity Score Based on 28 Joint Count (DAS28) who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Overall Study STARTED	43
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Measure	Rheumatoid Arthritis Participants Participants with moderate to severe rheumatoid arthritis (RA) according to the American College of Rheumatology (ACR) criteria and the Disease Activity Score Based on 28 Joint Count (DAS28) who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Lost to Follow-up	11

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Age, Continuous	44 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: ITT.

Outcome measures

Measure

Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.

Percentage of Participants Who Remained on Tocilizumab Treatment at 6 Months After Treatment Initiation

63 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 5

Population: ITT.

Percentage of participants was reported based on the timing RA was diagnosed. Timings included more than 5 years, less than 5 years. Participants with unknown timing were reported under "unknown".

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants With RA Diagnosis Less than 5 years	55.8 percentage of participants
Percentage of Participants With RA Diagnosis Unknown	4.6 percentage of participants
Percentage of Participants With RA Diagnosis More than 5 years	39.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 5

Population: ITT.

BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2). BMI from 16 to 18.5 = underweight, BMI from 18.5 to 25= normal weight, BMI from 25 to 30= overweight, BMI from 30 to 40 = obese.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants With Different Body Mass Index (BMI) Normal weight	39.5 percentage of participants
Percentage of Participants With Different Body Mass Index (BMI) Overweight	14 percentage of participants
Percentage of Participants With Different Body Mass Index (BMI) Obese	20.9 percentage of participants
Percentage of Participants With Different Body Mass Index (BMI) Underweight	25.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 5

Population: ITT.

Percentage of participants with rheumatoid factor status was reported as "positive" or "negative".

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants With Rheumatoid Factor Status Negative	58.1 percentage of participants
Percentage of Participants With Rheumatoid Factor Status Positive	41.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 5

Population: ITT.

Percentage of participants with anti-CCP status were reported as "positive", negative" and "unknown".

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants With Anti-Citrullinated Cyclic Peptide (Anti-CCP) Status Positive	81.4 percentage of participants
Percentage of Participants With Anti-Citrullinated Cyclic Peptide (Anti-CCP) Status Negative	11.6 percentage of participants
Percentage of Participants With Anti-Citrullinated Cyclic Peptide (Anti-CCP) Status Unknown	7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 1, 2, 3, 4, 5, 6

Population: ITT.

The DAS28 score is a measure of the participants' disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment (PtGA) of disease activity [visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 was calculated using following formulas: DAS28-ESR = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*PtGA of disease activity. A total possible score of 0 to approximately 10, with higher score indicating worse disease activity. A reduction of at least 2.6 units from Baseline in DAS28 was considered as significant clinical improvement.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 5	55.9 percentage of participants
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 6	63 percentage of participants
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 1	6.8 percentage of participants
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 2	12.5 percentage of participants
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 3	25.6 percentage of participants
Percentage of Participants With a Reduction of at Least 2.6 Units in DAS28 From Baseline Month 4	41.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Month 6

Population: ITT.

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 improvement from Baseline. Participants with a score less than or equal to (≤) 3.2 and DAS28 improvement of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score ≤3.2 and DAS28 improvement of >0.6 to ≤1.2 points, score of >3.2 and ≤5.1 with DAS28 improvement of >0.6 to ≤1.2 points, score of >3.2 and ≤5.1 with DAS28 improvement of >1.2 points, score of >5.1 and DAS28 improvement of >1.2 points were assessed as having a 'moderate' response. Participants with a score ≤3.2 and DAS28 improvement of ≤ 0.6 points, score of >3.2 and ≤5.1 with DAS28 improvement of ≤ 0.6 points, score of >5.1 and DAS28 improvement of >0.6 to ≤1.2 points, score of >5.1 and DAS28 improvement of ≤ 0.6 points were assessed as having a 'no' response.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Number of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria Good response	23 participants
Number of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria Moderate response	16 participants
Number of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria No response	4 participants

SECONDARY outcome

Timeframe: Baseline up to Month 6

Population: ITT.

The SDAI was calculated as [SJC (28 joints) + TJC (28 joints) + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity+CRP level(milligram/deciliter {mg/dL})]. VAS assessments: 0 centimeters (cm)=no disease activity to 10 cm=maximum disease activity'. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. SDAI score ≤ 3.3 is 'remission', score > 3.3 and ≤ 11 is 'low disease activity', score > 11 and ≤ 26 is 'moderate disease activity', score > 26 is 'high disease activity'. SDAI was reported as 'not available' for participants with no data on physical/patient global assessment of disease activity.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Number of Participants With Different Types of Simplified Disease Activity Index (SDAI) Remission	1 participants
Number of Participants With Different Types of Simplified Disease Activity Index (SDAI) Low disease activity	19 participants
Number of Participants With Different Types of Simplified Disease Activity Index (SDAI) Moderate disease activity	10 participants
Number of Participants With Different Types of Simplified Disease Activity Index (SDAI) High disease activity	4 participants
Number of Participants With Different Types of Simplified Disease Activity Index (SDAI) Not available	9 participants

SECONDARY outcome

Timeframe: Baseline up to Month 6

Population: ITT.

The CDAI was calculated as [SJC (28 joints) + TJC (28 joints) + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments: 0 cm =no disease activity to 100 cm=maximum disease activity'. CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. CDAI score ≤ 2.8 is 'remission', score > 2.8 and ≤ 10 is 'low disease activity', score > 10 and ≤ 22 is 'moderate disease activity', score > 22 is 'high disease activity'. CDAI was reported as 'not available' for participants with no data on physical/patient global assessment of disease activity.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Number of Participants With Different Types of Clinical Disease Activity Index (CDAI) Remission	1 participants
Number of Participants With Different Types of Clinical Disease Activity Index (CDAI) Low disease activity	19 participants
Number of Participants With Different Types of Clinical Disease Activity Index (CDAI) Moderate disease activity	11 participants
Number of Participants With Different Types of Clinical Disease Activity Index (CDAI) High disease activity	3 participants
Number of Participants With Different Types of Clinical Disease Activity Index (CDAI) Not available	9 participants

SECONDARY outcome

Timeframe: Month 1, 2, 3, 4, 5, 6

Population: ITT.

ACR20/50/70 percent (%) response is defined as a ≥ 20%/50%/70% improvement (reduction) compared with baseline for both TJC28 and SJC28, as well as for three of the additional five ACR core set variables: Participant's assessment of pain over the previous 24 hours: using a VAS, left end of the line 0 cm=no pain to right end of the line 10 cm=unbearable pain; Patient's global assessment of disease activity and physician's global assessment of disease activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; health assessment questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or erythrocyte sedimentation rate].

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 1	16.7 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 2	48.7 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 3	65.8 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 4	75.0 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 5	84.8 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR20: Month 6	84.6 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 1	4.8 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 2	15.4 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 3	31.6 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 4	61.2 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 5	63.7 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR50: Month 6	65.3 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 1	2.4 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 2	0.0 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 3	7.9 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 4	30.6 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 5	48.5 percentage of participants
Percentage of Participants Achieving a Response According to ACR Criteria ACR70: Month 6	53.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, up to Month 6

Population: ITT.

Participants with reduction/withdrawal of DMARDs and corticosteroids at baseline (before trial period) and up to Month 6 (during trial period) were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Number of Participants With Reduction/Withdrawal of Disease-modifying Anti-rheumatic Drugs (DMARDs) and/or Corticosteroids DMARDS: Baseline	16 participants
Number of Participants With Reduction/Withdrawal of Disease-modifying Anti-rheumatic Drugs (DMARDs) and/or Corticosteroids DMARDS: up to Month 6	1 participants
Number of Participants With Reduction/Withdrawal of Disease-modifying Anti-rheumatic Drugs (DMARDs) and/or Corticosteroids Corticosteroid: Baseline	1 participants
Number of Participants With Reduction/Withdrawal of Disease-modifying Anti-rheumatic Drugs (DMARDs) and/or Corticosteroids Corticosteroid: up to Month 6	1 participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6

Population: ITT. Here "number of participants analyzed" included evaluable participants for the outcome measure and "n" included evaluable participants at specified time point.

Physician's global assessment of disease activity over the previous 24 hours was assessed using a VAS where left end of the line 0 mm=no disease activity to right end of the line 100 mm=maximum disease activity.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=36 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Change From Baseline in Physician Global Assessment of Disease Activity at Months 3 and 6 Month 6 (n=0)	NA mm Standard Deviation NA Data was not reported as there were no evaluable participants for this time point.
Change From Baseline in Physician Global Assessment of Disease Activity at Months 3 and 6 Month 3 (n=36)	-29 mm Standard Deviation 3.11

SECONDARY outcome

Timeframe: Baseline up to Month 6

Population: ITT.

Outcome measures

Measure

Rheumatoid Arthritis Participants n=43 Participants Participants with moderate to severe RA according to the ACR criteria and the DAS28 who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.

Percentage of Participants With Tocilizumab Dose Modifications

33 percentage of participants

Adverse Events

Rheumatoid Arthritis Participants

Serious events: 14 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rheumatoid Arthritis Participants n=43 participants at risk Participants with moderate to severe RA and the DAS28 joint scores who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.
Gastrointestinal disorders Diarrhea	4.7% 2/43 • Baseline up to Month 6
General disorders Febris	2.3% 1/43 • Baseline up to Month 6
General disorders Severe pain	2.3% 1/43 • Baseline up to Month 6
Cardiac disorders Arrhythmia	2.3% 1/43 • Baseline up to Month 6
Gastrointestinal disorders Nausea	2.3% 1/43 • Baseline up to Month 6
Gastrointestinal disorders Vomiting	2.3% 1/43 • Baseline up to Month 6
Gastrointestinal disorders Gastropathy	4.7% 2/43 • Baseline up to Month 6
General disorders Dry Gangrene	2.3% 1/43 • Baseline up to Month 6
General disorders Left below knee lower limb amputation	2.3% 1/43 • Baseline up to Month 6
Vascular disorders Popliteal artery thrombosis	2.3% 1/43 • Baseline up to Month 6
General disorders Severe breakthrough back pain	2.3% 1/43 • Baseline up to Month 6
Nervous system disorders Syncope	2.3% 1/43 • Baseline up to Month 6

Other adverse events

Measure

Rheumatoid Arthritis Participants n=43 participants at risk Participants with moderate to severe RA and the DAS28 joint scores who were on tocilizumab treatment within 8 weeks prior to start of study received tocilizumab in accordance with the licensed label recommendations, were observed for 6 months. The study was designed as non-interventional, no additional intervention in terms of follow-up visit, complementary examination or medication was required.

Blood and lymphatic system disorders Neutropenia

7.0% 3/43 • Baseline up to Month 6

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER