Trial Outcomes & Findings for A Non-Interventional Study Evaluating Rheumatoid Arthritis Participants Treated With Tocilizumab (RoActemra/Actemra) (NCT NCT01671059)

NCT ID: NCT01671059

Last Updated: 2017-02-23

Results Overview

• Recruitment status: COMPLETED
• Target enrollment: 80 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2017-02-23

Participant Flow

Participant milestones

Measure	Tocilizumab Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Overall Study STARTED	80
Overall Study COMPLETED	75
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Tocilizumab Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Overall Study Adverse Event	4
Overall Study Lack of Efficacy	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Age, Continuous	50.6 years STANDARD_DEVIATION 11.98 • n=5 Participants
Gender Female	67 Participants n=5 Participants
Gender Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Enrolled participants.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants on Tocilizumab 6 Months After Treatment Initiation	93.75 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants With Dose Modifications	11.2 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

Outcome measures

Measure	Tocilizumab n=73 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants Receiving Tocilizumab After Failing Disease-Modifying Anti-Rheumatic Drugs (DMARDs)	81.35 percentage of participants

SECONDARY outcome

Timeframe: Baseline

Population: Enrolled participants.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants Receiving Tocilizumab After Failing Other Biologic Agents	18.8 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Reasons for Dose Modifications Adverse event	3 participants
Reasons for Dose Modifications Low level of neutrophils	1 participants
Reasons for Dose Modifications Other reason	1 participants
Reasons for Dose Modifications Missing data	1 participants
Reasons for Dose Modifications Unknown reason	3 participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants With Dose Interruptions	3.75 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy Adverse Event	3 percentage of participants
Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy Lack of Efficacy	1 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

Outcome measures

Measure	Tocilizumab n=73 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants on Tocilizumab Monotherapy at Study Entry	13.6 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Disease Activity Score Based on 28-Joint Count (DAS28) Combination therapy	2.78 units on a scale Interval 0.51 to 5.25
Disease Activity Score Based on 28-Joint Count (DAS28) Monotherapy	2.45 units on a scale Interval 0.63 to 5.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants on Combination Therapy Achieving a Response by European League Against Rheumatism (EULAR) Category Good response	62.3 percentage of participants
Percentage of Participants on Combination Therapy Achieving a Response by European League Against Rheumatism (EULAR) Category Moderate response	32.1 percentage of participants
Percentage of Participants on Combination Therapy Achieving a Response by European League Against Rheumatism (EULAR) Category No response	5.7 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants on Monotherapy Achieving a Response by European League Against Rheumatism (EULAR) Category Good response	71.4 percentage of participants
Percentage of Participants on Monotherapy Achieving a Response by European League Against Rheumatism (EULAR) Category Moderate response	28.6 percentage of participants
Percentage of Participants on Monotherapy Achieving a Response by European League Against Rheumatism (EULAR) Category No response	0.0 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Simplified Disease Activity Index (SDAI) Combination therapy	6.69 units on a scale Interval 0.03 to 27.2
Simplified Disease Activity Index (SDAI) Monotherapy	4.5 units on a scale Interval 1.3 to 20.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Clinical Disease Activity Index (CDAI) Score Combination therapy	7.05 units on a scale Interval 0.0 to 27.0
Clinical Disease Activity Index (CDAI) Score Monotherapy	6 units on a scale Interval 1.0 to 20.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants With American College of Rheumatology (ACR) Response ACR20 Response: Combination therapy	87.8 percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) Response ACR20 Response: Monotherapy	100 percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) Response ACR50 Response: Combination therapy	46.3 percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) Response ACR50 Response: Monotherapy	66.6 percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) Response ACR70 Response: Combination therapy	41.4 percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) Response ACR70 Response: Monotherapy	33.3 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants.

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.

Outcome measures

Measure	Tocilizumab n=80 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) AE	25 percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) SAE	13.75 percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) AESI	1.25 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Patient Global Assessment of Disease Activity Score Combination therapy	15 units on a scale Interval 0.0 to 80.0
Patient Global Assessment of Disease Activity Score Monotherapy	14 units on a scale Interval 0.0 to 30.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Health Assessment Questionnaire Disability Index (HAQ-DI) Combination therapy	0.43 units on a scale Interval 0.0 to 2.13
Health Assessment Questionnaire Disability Index (HAQ-DI) Monotherapy	0.43 units on a scale Interval 0.1 to 2.37

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Visual Analogue Scale (VAS) for Fatigue Combination therapy	15 units on a scale Interval 0.0 to 70.0
Visual Analogue Scale (VAS) for Fatigue Monotherapy	11 units on a scale Interval 0.0 to 30.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Visual Analogue Scale (VAS) for Morning Stiffness Combination therapy	10 units on a scale Interval 0.0 to 100.0
Visual Analogue Scale (VAS) for Morning Stiffness Monotherapy	12 units on a scale Interval 0.0 to 30.0

SECONDARY outcome

Timeframe: 6 months

Population: Enrolled participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	Tocilizumab n=79 Participants Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Visual Analogue Scale (VAS) for Pain Combination therapy	20 units on a scale Interval 0.0 to 80.0
Visual Analogue Scale (VAS) for Pain Monotherapy	20 units on a scale Interval 0.0 to 30.0

Adverse Events

Tocilizumab

Serious events: 11 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab n=80 participants at risk Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Injury, poisoning and procedural complications Pelvic fracture	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Injury, poisoning and procedural complications Acetabulum fracture	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Injury, poisoning and procedural complications Limb injury	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Injury, poisoning and procedural complications Medication error	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Infections and infestations Oral herpes	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Infections and infestations Arthritis bacterial	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Infections and infestations Pneumonia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Blood and lymphatic system disorders Neutropenia	2.5% 2/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Blood and lymphatic system disorders Leukopenia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Alanine aminotransferase increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Aspartate aminotransferase increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Transaminases increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Neutrophil count decreased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Other adverse events

Measure	Tocilizumab n=80 participants at risk Participants with rheumatoid arthritis (RA) receiving tocilizumab either as combination therapy or monotherapy through routine clinical practice.
Investigations Aspartate aminotransferase increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Alanine aminotransferase increased	2.5% 2/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Transaminases increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Thrombocytopenia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Blood cholesterol increased	2.5% 2/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Blood triglycerides increased	2.5% 2/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigations Gamma-Glutamyltransferase increased	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Infections and infestations Tonsillitis	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Gastrointestinal disorders Abdominal pain	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Reproductive system and breast disorders Gynaecomastia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Metabolism and nutrition disorders Hyperlipidaemia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Blood and lymphatic system disorders Neutropenia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Blood and lymphatic system disorders Leukopenia	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Skin and subcutaneous tissue disorders Diabetic foot	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.
General disorders Lack of drug effect	1.2% 1/80 • 6 months An adverse event is any unfavorable or unintended sign or symptom associated with the use of a medicinal product, whether or not considered related to the medicinal product.

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