Trial Outcomes & Findings for A Retrospective Chart Review on the Use of Biologics in Monotherapy for the Treatment of Patients With Rheumatoid Arthritis (NCT NCT01640548)

NCT ID: NCT01640548

Last Updated: 2016-11-02

Results Overview

bDMARDS for RA treatment include etanercept, adalimumab, tocilizumab, rituximab, certolizumab pegol, infliximab, golimumab, abatacept and anakinra medications. Current bDMARDs were defined as those with a start date on or after the date of collection, or those with a start date before the date of collection and an end date on or after the date of collection. NICE guidelines recommend the participants with severe active RA who inadequately responded to prior DMARD treatment (trial of 2 DMARDs, one which includes methotrexate) and were intolerant to methotrexate or the treatment with methotrexate considered inappropriate be treated with a biologic DMARD monotherapy.

• Recruitment status: COMPLETED
• Target enrollment: 320 participants
• Primary outcome timeframe: 9 months
• Results posted on: 2016-11-02

Participant Flow

Participant milestones

Measure	Rheumatoid Arthritis (RA) Cohort Participants on biologic disease modifying anti-rheumatic drug (bDMARD) monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Overall Study STARTED	309
Overall Study COMPLETED	309
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Retrospective Chart Review on the Use of Biologics in Monotherapy for the Treatment of Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Rheumatoid Arthritis Cohort n=309 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Age, Continuous	61.8 years STANDARD_DEVIATION 11.99 • n=5 Participants
Gender Female	224 Participants n=5 Participants
Gender Male	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: 9 months

Population: Included all the participants who entered the retrospective chart review.

bDMARDS for RA treatment include etanercept, adalimumab, tocilizumab, rituximab, certolizumab pegol, infliximab, golimumab, abatacept and anakinra medications. Current bDMARDs were defined as those with a start date on or after the date of collection, or those with a start date before the date of collection and an end date on or after the date of collection. NICE guidelines recommend the participants with severe active RA who inadequately responded to prior DMARD treatment (trial of 2 DMARDs, one which includes methotrexate) and were intolerant to methotrexate or the treatment with methotrexate considered inappropriate be treated with a biologic DMARD monotherapy.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=309 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Etanercept	39.5 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Adalimumab	28.8 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Tocilizumab	12.3 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Rituximab	10.7 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Certolizumab Pegol	6.1 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Infliximab	1.0 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Golimumab	1.0 percentage of participants
Percentage (%) of Participants Receiving Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Monotherapy as Current Treatment for RA According to National Institute for Health and Clinical Excellence (NICE) Guidelines by Type of bDMARD Abatacept	0.6 percentage of participants

PRIMARY outcome

Timeframe: 9 months

Population: Included all the participants who took any past traditional DMARDs.

Traditional DMARDS for RA treatment include methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold compounds, penicillamine, cyclosporine, azathioprine, chlorambucil, mercaptopurine, and mycophenolate mofetil medications. Previous RA treatment included all the treatments received prior to switching to current RA treatment.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=303 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Methotrexate	94.7 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Sulfasalazine	78.9 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Leflunomide	46.9 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Hydroxychloroquine	42.9 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Gold Compounds	29.4 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Penicillamine	9.9 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Cyclosporine	9.2 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Azathioprine	8.9 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Chlorambucil	0.3 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Mercaptopurine	0.3 percentage of participants
Percentage of Participants Treated With Traditional DMARDs as Their Previous Treatment for RA by Type of DMARD Mycophenolate Mofetil	0.3 percentage of participants

PRIMARY outcome

Timeframe: 9 months

Population: Included participants who were previously treated with any bDMARD with concomitant traditional DMARD prior to switch to bDMARD monotherapy as current RA treatment.

bDMARDS for RA treatment include etanercept, adalimumab, tocilizumab, rituximab, certolizumab pegol, infliximab, golimumab, abatacept and anakinra medications. Only the most frequently used (> 10% of participants) bDMARDs with concomitant traditional DMARD as previous treatment for RA were reported. If a participant was recorded to have been treated with a single bDMARD more than once, the participant was counted only once per type of bDMARD. If participant received 2 different types of bDMARDs as part of their previous treatment, the participant was counted twice, once per each type of bDMARD; therefore, the percentage of participants did not add up to 100%.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=131 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Abatacept	1.5 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Anakinra	0.8 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Etanercept	51.9 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Adalimumab	45.0 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Rituximab	16.8 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Infliximab	15.3 percentage of participants
Percentage of Participants With bDMARD and Concomitant Traditional DMARD Regimen as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy by Type of bDMARD Tocilizumab	9.2 percentage of participants

PRIMARY outcome

Timeframe: 9 months

Population: Included participants who received bDMARD as monotherapy as previous treatment prior to switch to bDMARD monotherapy as current treatment.

bDMARDS for RA treatment include etanercept, adalimumab, tocilizumab, rituximab, certolizumab pegol, infliximab, golimumab, abatacept and anakinra medications. Only the most frequently used (> 10% of participants) bDMARDs in monotherapy as previous treatment for RA were reported. If a participant was recorded to have been treated with a single bDMARD more than once, the participant was counted only once per type of bDMARD. If participant received 2 different types of bDMARDs as part of their previous treatment, the participant was counted twice, once per each type of bDMARD; therefore, the percentage of participants did not add up to 100%.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=117 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage of Participants With bDMARD Monotherapy as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy Etanercept	53.0 percentage of participants
Percentage of Participants With bDMARD Monotherapy as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy Adalimumab	41.9 percentage of participants
Percentage of Participants With bDMARD Monotherapy as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy Certolizumab Pegol	13.7 percentage of participants
Percentage of Participants With bDMARD Monotherapy as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy Rituximab	11.1 percentage of participants
Percentage of Participants With bDMARD Monotherapy as Previous RA Treatment at Anytime Prior to Switch to bDMARD Monotherapy Tocilizumab	6.0 percentage of participants

PRIMARY outcome

Timeframe: 9 months

Population: Included all the participants who entered the retrospective chart review.

All corticosteroids and non-steroidal anti-inflammatory drugs taken as previous and current treatments for RA were coded according to the Roche international non-proprietary name dictionary.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=309 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage of Participants With Concomitant Treatment Other Than DMARDs for RA by Type of Treatment Participants with any previous treatment for RA	96.1 percentage of participants
Percentage of Participants With Concomitant Treatment Other Than DMARDs for RA by Type of Treatment Non-steroidal anti-inflammatories	83.8 percentage of participants
Percentage of Participants With Concomitant Treatment Other Than DMARDs for RA by Type of Treatment Corticosteroids	77.3 percentage of participants

PRIMARY outcome

Timeframe: 9 months

Population: Included all participants who entered the retrospective chart review.

Both previous and current bDMARDs were presented together for each subgroup, therefore the percentage of participants under each reason did not add up to 100%.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=309 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Percentage of Participants by Reason for Choosing Previous and Current bDMARDs in Monotherapy Physician's preference/experience/Unknown	84.1 percentage of participants Interval 79.6 to 88.0
Percentage of Participants by Reason for Choosing Previous and Current bDMARDs in Monotherapy Participant preference	5.8 percentage of participants Interval 3.5 to 9.1
Percentage of Participants by Reason for Choosing Previous and Current bDMARDs in Monotherapy Contra-indication to alternative drug	4.9 percentage of participants Interval 2.7 to 7.9
Percentage of Participants by Reason for Choosing Previous and Current bDMARDs in Monotherapy Other	8.4 percentage of participants Interval 5.6 to 12.1

SECONDARY outcome

Timeframe: 9 months

Population: Included the number of participants who were evaluable for DAS28 assessment. "n" represents the number of participants who were evaluable for that particular assessment.

DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, ESR (in millimeters/hour) or CRP (in milligrams/liter), and the participant's global assessment of disease activity (visual analog scale: 0=no disease activity to 100=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56 x square root (√) of TJC + 0.28 x √(SJC) + 0.70 x log natural (ESR) + 0.014 x global assessment of RA score. The formula for calculating DAS28 score using CRP value is: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x log natural (CRP+1) + 0.014 x global assessment of RA score +0.96. The DAS28 score range was 0-9.4 where higher scores represented higher disease activity.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=149 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Assessment of Disease Activity Score of 28 Joint Count (DAS28) by Either Erythrocyte Sedimentation Ratio (ESR) or C-Reactive Protein (CRP) ESR-DAS28 score (n=149)	3.41 scores on a scale Interval 3.16 to 3.66
Assessment of Disease Activity Score of 28 Joint Count (DAS28) by Either Erythrocyte Sedimentation Ratio (ESR) or C-Reactive Protein (CRP) CRP-DAS28 score (n=72)	3.21 scores on a scale Interval 2.84 to 3.58

SECONDARY outcome

Timeframe: 9 months

Population: Includes all participants who were evaluable for this outcome. "n" represents the number of participants who were evaluable for that particular assessment.

DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, ESR (in millimeters/hour) or CRP (in milligrams/liter), and the participant's global assessment of disease activity (visual analog scale: 0=no disease activity to 100=maximum disease activity). TJC and SJC assessed as part of the DAS28 outcome measure assessment were reported.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=164 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods ESR-TJC (n=164)	3.2 joints count Interval 2.4 to 4.0
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods ESR-SJC (n=163)	1.6 joints count Interval 1.2 to 2.0
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods ESR-Non-evaluable DAS28 joints (n=125)	0.4 joints count Interval 0.1 to 0.8
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods CRP-TJC (n=73)	3.7 joints count Interval 2.4 to 4.9
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods CRP-SJC (n=74)	2.3 joints count Interval 1.5 to 3.2
Total Number of Tender Joints and Swollen Joints and Non-Evaluable DAS 28 Joints When Assessed Using Both ESR and CRP Methods CRP-Non-evaluable DAS28 joints (n=30)	0.5 joints count Interval 0.2 to 0.8

SECONDARY outcome

Timeframe: 9 months

Population: Included all participants who received bDMARD monotherapy as their current treatment for RA. "n is the number of participants who received that particular bDMARD as their current RA treatment.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=308 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Duration of Treatment With the Current bDMARD Usage in Monotherapy Abatacept (n=2)	38.70 months Interval 10.3 to 67.1
Duration of Treatment With the Current bDMARD Usage in Monotherapy Adalimumab (n=89)	41.70 months Interval 1.1 to 148.2
Duration of Treatment With the Current bDMARD Usage in Monotherapy Certolizumab Pegol (n=19)	13.20 months Interval 1.1 to 26.0
Duration of Treatment With the Current bDMARD Usage in Monotherapy Etanercept (n=121)	36.20 months Interval 1.7 to 145.1
Duration of Treatment With the Current bDMARD Usage in Monotherapy Golimumab (n=3)	6.60 months Interval 0.8 to 20.3
Duration of Treatment With the Current bDMARD Usage in Monotherapy Infliximab (n=3)	13.60 months Interval 0.2 to 32.0
Duration of Treatment With the Current bDMARD Usage in Monotherapy Rituximab (n=33)	18.20 months Interval 1.1 to 71.1
Duration of Treatment With the Current bDMARD Usage in Monotherapy Tocilizumab (n=38)	12.05 months Interval 0.1 to 54.7

SECONDARY outcome

Timeframe: 9 months

Population: Included participants treated with a bDMARD monotherapy as previous treatment for RA prior to switch to current bDMARD monotherapy. "n" is the number of participants who received particular bDMARD as previous RA treatment.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=117 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Duration of Treatment With bDMARDs in Monotherapy as Previous Treatment for RA Etanercept (n=82)	10.50 months Interval 0.5 to 123.0
Duration of Treatment With bDMARDs in Monotherapy as Previous Treatment for RA Rituximab (n=14)	4.25 months Interval 0.5 to 44.0
Duration of Treatment With bDMARDs in Monotherapy as Previous Treatment for RA Tocilizumab (n=7)	7.80 months Interval 0.9 to 14.1
Duration of Treatment With bDMARDs in Monotherapy as Previous Treatment for RA Adalimumab (n=56)	8.55 months Interval 0.4 to 102.5
Duration of Treatment With bDMARDs in Monotherapy as Previous Treatment for RA Certolizumab Pegol (n=16)	0.90 months Interval 0.6 to 12.0

SECONDARY outcome

Timeframe: 9 months

Population: Included participants who were treated with a bDMARD with concomitant traditional DMARD as previous treatment for RA. "n" is the number of participants who received particular bDMARD as previous RA treatment.

Outcome measures

Measure	Rheumatoid Arthritis Cohort n=131 Participants Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Abatacept (n=2)	4.10 months Interval 2.9 to 5.3
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Adalimumab (n=62)	18.60 months Interval 1.2 to 107.9
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Anakinra (n=1)	9.50 months Interval 9.5 to 9.5
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Etanercept (n=72)	15.95 months Interval 0.7 to 87.2
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Infliximab (n=21)	10.00 months Interval 0.0 to 106.3
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Rituximab (n=41)	0.00 months Interval 0.0 to 37.2
Duration of Treatment of bDMARD Administered With Concomitant Traditional DMARD as Previous Treatment for RA Tocilizumab (n=15)	3.40 months Interval 0.0 to 31.6

Adverse Events

Rheumatoid Arthritis Cohort

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rheumatoid Arthritis Cohort n=71 participants at risk Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Infections and infestations Lower Respiratory Tract Infection	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Infections and infestations Necrotising fascitis	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Hepatobiliary disorders Cholecystitis	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.

Other adverse events

Measure	Rheumatoid Arthritis Cohort n=71 participants at risk Participants on bDMARD monotherapy for RA and on any RA treatment in the past were observed and data was collected retrospectively from a chart review for approximately 9 months.
Skin and subcutaneous tissue disorders Drug eruption	2.8% 2/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Skin and subcutaneous tissue disorders Rash	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Hepatobiliary disorders Hepatitis	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.
Blood and lymphatic system disorders Neutropenia	1.4% 1/71 • 9 months Adverse events data were collected retrospectively for participants treated with rituximab or tocilizumab only.

Additional Information

Medical Communications

Hoffmann-LaRoche

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