Trial Outcomes & Findings for A Retrospective, Observational Chart Review of Biologics in Monotherapy Versus the Combination Biologic Plus Methotrexate in Patients With Rheumatoid Arthritis (NCT NCT01866150)

Last Updated: 2015-10-05

Results Overview

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], participant's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. DAS28 equals (=) (0.56 multiplied by \[\*\] the square root \[√\] of TJC) plus (+) (0.28 \* √ of SJC) + (0.70 \* the natural logarithm \[ln\] ESR in millimeters per hour \[mm/h\]) + (0.014 \* participant's global assessment of disease activity). DAS28 Remission is defined as a DAS28 score \<2.6.

Recruitment status

COMPLETED

Target enrollment

476 participants

Primary outcome timeframe

Month 6

Results posted on

2015-10-05

Participant Flow

Retrospective data was collected for 450 participants of whom 151 received biologic monotherapy, 289 received biologic combination therapy and 10 could not be categorized. Participant flow and baseline characteristics are presented for overall population and endpoints are presented for individual group.

Participant milestones

Participant milestones
Measure	Overall Population Retrospective chart review of all participants with rheumatoid arthritis (RA) who were being treated with first-line biologic drug therapy (any) as monotherapy or biologic combination therapy according to National Institute for Health and Care Excellence (NICE) guidelines. Biologic combination therapy included biologic drug therapy (any) plus methotrexate (MTX) or biologic plus MTX plus any other and classical disease-modifying antirheumatic drugs (DMARDs).
Overall Study STARTED	450
Overall Study COMPLETED	450
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Retrospective, Observational Chart Review of Biologics in Monotherapy Versus the Combination Biologic Plus Methotrexate in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Population n=450 Participants Retrospective chart review of all participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy or biologic combination therapy according to NICE guidelines. Biologic combination therapy included biologic drug therapy (any) plus MTX or biologic plus MTX plus any other and classical DMARDs.
Age, Continuous	61.5 years STANDARD_DEVIATION 11.53 • n=5 Participants
Sex: Female, Male Female	331 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: Ten participants from all participants entered analysis set who could not be categorized as under biologic monotherapy or biologic combination therapy were excluded from analysis. Number of participants analyzed=participants with available data for DAS28-ESR at Month 6.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=114 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=191 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Percentage of Participants Who Achieved Disease Activity Score Based on 28-joint Count (DAS-28) and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at 6 Months (DAS28<2.6)	30.7 percentage of participants	31.9 percentage of participants

SECONDARY outcome

Timeframe: Month 3 and the last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the ESR for a total possible score of 0 to approximately 10. DAS28 = (0.56 \* √ of TJC) + (0.28 \* √ of SJC) + (0.70 \* ln ESR in mm/h) + (0.014 \* participant's global assessment of disease activity). DAS28 Remission is defined as a DAS28 score \< 2.6.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=133 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=243 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Percentage of Participants Who Achieved DAS28-ESR Remission (DAS28-ESR <2.6) at 3 Months and at the Last Visit After Initiation of First-Line Biologic Treatment Month 3 (n=113,214)	23.9 percentage of participants	27.6 percentage of participants
Percentage of Participants Who Achieved DAS28-ESR Remission (DAS28-ESR <2.6) at 3 Months and at the Last Visit After Initiation of First-Line Biologic Treatment Last visit (n=133,243)	44.4 percentage of participants	46.9 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6 and last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the ESR for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \<2.6. LDA was defined as a DAS28 score \<3.2.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=133 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=243 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Percentage of Participants Who Achieved Low Disease Activity (LDA) (DAS28-ESR <3.2) at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Month 3 (n=113,214)	42.5 percentage of participants	41.6 percentage of participants
Percentage of Participants Who Achieved Low Disease Activity (LDA) (DAS28-ESR <3.2) at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Month 6 (n=114,191)	50.0 percentage of participants	53.4 percentage of participants
Percentage of Participants Who Achieved Low Disease Activity (LDA) (DAS28-ESR <3.2) at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Last visit (n=133,243)	57.1 percentage of participants	67.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 3, 6 and last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and either ESR or C Reactive Protein (CRP) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \<2.6.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=115 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=215 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Change From Baseline in DAS28 at Months 3, 6 and at The Last Visit After Initiation of First-Line Biologic Treatment Month 3 (n=103,198)	-2.74 units on a scale Standard Error 0.123	-2.84 units on a scale Standard Error 0.089
Change From Baseline in DAS28 at Months 3, 6 and at The Last Visit After Initiation of First-Line Biologic Treatment Month 6 (n=105,180)	-3.00 units on a scale Standard Error 0.119	-3.18 units on a scale Standard Error 0.089
Change From Baseline in DAS28 at Months 3, 6 and at The Last Visit After Initiation of First-Line Biologic Treatment Last visit (n=115,215)	-3.39 units on a scale Standard Error 0.124	-3.54 units on a scale Standard Error 0.091

SECONDARY outcome

Timeframe: Baseline, Month 3, 6 and last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and either ESR or CRP for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \<2.6.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=136 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=254 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Percentage of Participants by Category of DAS28 Score and Timepoint Baseline: <2.6 (n=117,219)	2.6 percentage of participants	0.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Baseline: ≥2.6 to ≤3.2 (n=117,219)	0.9 percentage of participants	0.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Baseline: >3.2 (n=117,219)	96.6 percentage of participants	99.1 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Baseline: >4 (n=117,219)	95.7 percentage of participants	98.2 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 3: <2.6 (n=117,222)	24.1 percentage of participants	27.9 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 3: ≥2.6 to ≤3.2 (n=117,222)	19.8 percentage of participants	17.6 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 3: >3.2 (n=117,222)	56.0 percentage of participants	54.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 3: >4 (n=117,222)	37.1 percentage of participants	32.9 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 6: <2.6 (n=117,200)	29.9 percentage of participants	30.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 6: ≥2.6 to ≤3.2 (n=117,200)	23.1 percentage of participants	24.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 6: >3.2 (n=117,200)	47.0 percentage of participants	45.0 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Month 6: >4 (n=117,200)	29.9 percentage of participants	22.5 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Last visit: <2.6 (n=136,254)	44.1 percentage of participants	46.9 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Last visit: ≥2.6 to ≤3.2 (n=136,254)	18.4 percentage of participants	23.2 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Last visit: >3.2 (n=136,254)	37.5 percentage of participants	29.9 percentage of participants
Percentage of Participants by Category of DAS28 Score and Timepoint Last visit: >4 (n=136,254)	20.6 percentage of participants	15.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

Drug retention was defined as the total duration of time in months the participant was on treatment (combination therapy or monotherapy). The duration was the time in months between the start date of biologic therapy to the date of most recent visit.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=131 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=247 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Duration of Treatment	57.30 months Standard Deviation 38.227	48.48 months Standard Deviation 34.619

SECONDARY outcome

Timeframe: Baseline up to last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

Population: Participants in biologic combination group from All Participants Entered Analysis Set. Number of participants analyzed=participants with available data for methotrexate dose.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=178 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Average Methotrexate Dose of Participants on Biological Combination Treatment	17.12 milligrams per week Standard Deviation 5.64	—

SECONDARY outcome

Timeframe: Baseline, Month 3, 6 and last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The 28 joints to be assessed for tenderness were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=129 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=245 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Change From Baseline in Total Number of Tender Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Baseline (n=129,245)	17.1 tender joints Standard Deviation 6.98	16.3 tender joints Standard Deviation 7.21
Change From Baseline in Total Number of Tender Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Change from baseline at Month 3 (n=106,203)	-12.5 tender joints Standard Deviation 7.72	-12.4 tender joints Standard Deviation 6.95
Change From Baseline in Total Number of Tender Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Change from baseline at Month 6 (n=107,184)	-14.4 tender joints Standard Deviation 6.93	-13.4 tender joints Standard Deviation 7.51
Change From Baseline in Total Number of Tender Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment. Change from baseline at Last visit (n=114,215)	-14.9 tender joints Standard Deviation 8.18	-14.3 tender joints Standard Deviation 7.28

SECONDARY outcome

Timeframe: Baseline, Month 3, 6 and last visit (maximum 147.1 months for monotherapy and 189.1 months for combination therapy)

The 28 joints to be assessed for swelling were shoulder, elbow, wrist, MCP joints 1-5, PIP joints 1-5, and knee on both sides of the body. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Outcome measures

Outcome measures
Measure	Biologic Monotherapy n=129 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) as monotherapy according to NICE guidelines.	Biologic Combination n=246 Participants Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (any) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
Change From Baseline in Total Number of Swollen Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment Baseline (n=129,246)	9.1 swollen joints Standard Deviation 5.27	10.0 swollen joints Standard Deviation 5.64
Change From Baseline in Total Number of Swollen Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment Change From Baseline at Month 3 (n=106,205)	-7.0 swollen joints Standard Deviation 5.05	-7.2 swollen joints Standard Deviation 5.10
Change From Baseline in Total Number of Swollen Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment Change From Baseline at Month 6 (n=107,185)	-7.7 swollen joints Standard Deviation 5.24	-8.3 swollen joints Standard Deviation 5.57
Change From Baseline in Total Number of Swollen Joints at Months 3 and 6 and at the Last Visit After Initiation of First-Line Biologic Treatment Change From Baseline at Last Visit (n=114,216)	-7.9 swollen joints Standard Deviation 5.73	-8.8 swollen joints Standard Deviation 5.64

Adverse Events

Biologic Monotherapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Biologic Combination

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Biologic Monotherapy n=7 participants at risk Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (only rituximab or tocilizumab) as monotherapy according to NICE guidelines.	Biologic Combination n=9 participants at risk Retrospective chart review of participants with RA who were being treated with first-line biologic drug therapy (only rituximab or tocilizumab) plus MTX or biologic plus MTX plus any other classical DMARDs according to NICE guidelines.
General disorders Fatigue	0.00% 0/7 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.	11.1% 1/9 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.
General disorders Influenza Like Illness	0.00% 0/7 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.	11.1% 1/9 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.
Ear and labyrinth disorders Ear Pruritus	0.00% 0/7 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.	11.1% 1/9 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.
Infections and infestations Nasopharyngitis	0.00% 0/7 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.	11.1% 1/9 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.
Vascular disorders Hot Flush	0.00% 0/7 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.	11.1% 1/9 • Baseline up to the last visit after initiation of first line biologic treatment (maximum 147.1 months for monotherapy and 189.1 months for combination therapy) Adverse events data were planned to be collected only for those participants who received rituximab or tocilizumab, as biologic therapy.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800 821-8590

Email: [email protected]

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