Trial Outcomes & Findings for Study to Assess the Safety and Efficacy of Etanercept in Patients Treated Over the Long-term in Real-world Clinical Practice, Using Data Collected by the British Society of Rheumatology Biologics Registry (NCT NCT01646385)

Last Updated: 2014-08-05

Results Overview

Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by mean follow-up in years). Crude (unadjusted) incidence rate calculated as number of malignancy events divided by Participant-Year, multiplied by 1000.

Recruitment status

COMPLETED

Target enrollment

6393 participants

Primary outcome timeframe

Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Results posted on

2014-08-05

Participant Flow

Participant milestones

Participant milestones
Measure	Etanercept Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Overall Study STARTED	3529	2864
Overall Study COMPLETED	2691	1993
Overall Study NOT COMPLETED	838	871

Reasons for withdrawal

Reasons for withdrawal
Measure	Etanercept Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Overall Study Death	202	222
Overall Study Switched to alternate biologic	636	649

Baseline Characteristics

Study to Assess the Safety and Efficacy of Etanercept in Patients Treated Over the Long-term in Real-world Clinical Practice, Using Data Collected by the British Society of Rheumatology Biologics Registry

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.	Total n=6393 Participants Total of all reporting groups
Age, Continuous	55.3 years STANDARD_DEVIATION 12.1 • n=99 Participants	59.8 years STANDARD_DEVIATION 12.4 • n=107 Participants	57.3 years STANDARD_DEVIATION 12.4 • n=206 Participants
Sex: Female, Male Female	2727 Participants n=99 Participants	2135 Participants n=107 Participants	4862 Participants n=206 Participants
Sex: Female, Male Male	802 Participants n=99 Participants	729 Participants n=107 Participants	1531 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Population: Safety analysis population included all participants treated with ETN or nbDMARDs who had a physician diagnosis of rheumatoid arthritis and a minimum of one consultant follow-up after baseline registration.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Crude Incidence Rate of Malignancy	14.7 events per 1000 participant-years	23.9 events per 1000 participant-years

PRIMARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Participant-Year estimated by calculating all of years that participants in a study were followed (number of evaluable participants multiplied by mean follow-up in years). Crude (unadjusted) incidence rate calculated as number of LMs divided by Participant-Year, multiplied by 1000. Lymphoproliferative: medical condition characterized by the dysfunction of the immune system often resulting in excessive production of lymphocytes. LMs included lymphoma, myeloma, and leukemia. Adverse outcome was defined as 'lymphoproliferative malignancy' in the field \[lymphopro\] labeled by BSRBR.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Crude Incidence Rate of Lymphoproliferative Malignancy (LM)	1.1 events per 1000 participant-years	2.6 events per 1000 participant-years

PRIMARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of serious infections divided by Participant-Year, multiplied by 1000. Serious infections included those infections which required intravenous antibiotics, hospitalization, or resulted in death. Adverse outcome was defined as 'serious infection' in the field \[serinf\] labeled by BSRBR.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Crude Incidence Rate of Serious Infections	35.1 events per 1000 participant-years	36.2 events per 1000 participant-years

PRIMARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of other serious adverse events divided by Participant-Year, multiplied by 1000. Other serious adverse events were based on classifications assigned by the BSRBR and included cardiac serious adverse events (SAEs), central nervous system SAEs, and nonmalignant hematological SAEs.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Crude Incidence Rate of Other Serious Adverse Events	20.3 events per 1000 participant-years	29.6 events per 1000 participant-years

PRIMARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of deaths divided by Participant-Year, multiplied by 1000. Death was recorded in the adverse outcomes table and in the consultant follow-up table. Where multiple events described death for the same participant, date of death was taken as per the earliest record.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Crude Incidence Rate of All-Cause Mortality	12.0 events per 1000 participant-years	20.1 events per 1000 participant-years

SECONDARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Population: Full Analysis set (FAS) population included all participants treated with ETN or nbDMARDs who had a physician diagnosis of rheumatoid arthritis and a minimum of one consultant follow-up after baseline registration. Only participants treated with ETN were to be analyzed for this outcome measure.

Participants who switched from etanercept to either DMARDs or alternative biologic drug are reported.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Percentage of Participants Who Switched to Other Therapy Following Etanercept Discontinuation Switched to DMARDs	35.3 percentage of participants	—
Percentage of Participants Who Switched to Other Therapy Following Etanercept Discontinuation Switched to alternative biologic	18.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Population: FAS population included all participants treated with ETN or nbDMARDs who had a physician diagnosis of rheumatoid arthritis and a minimum of one consultant follow-up after baseline registration. Only participants treated with ETN were to be analyzed for this outcome measure.

Time on etanercept therapy was calculated by Kaplan-Meier survival analysis.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Time on Etanercept Therapy	4.959 years Interval 4.539 to 5.379	—

SECONDARY outcome

Timeframe: Baseline

DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the serological markers of inflammation (erythrocyte sedimentation rate \[ESR, millimeter per hour\] or C-reactive protein \[CRP, milligram per liter\]) and patient's general health assessment (recorded on a Visual Analog Scale \[VAS\] of 0 millimeter \[mm\]-100 mm). DAS28 \<=1.6 = remission, DAS28 \<=2.4 = low disease activity, DAS28 \>=3.2 to 5.1 = moderate disease activity, DAS28 \>5.1 = severe disease activity.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Disease Activity Score Based on 28-Joints Count (DAS28) at Baseline	6.6 units on a scale Standard Deviation 1.0	5.6 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline, Year 1, 2, 3, 4, 5

Population: FAS included all participants treated with ETN or nbDMARDs who had a physician diagnosis of rheumatoid arthritis and a minimum of 1 consultant follow-up after baseline registration. N (number of participants analyzed): participants evaluable for this measure, n: participants evaluable for specified time-points for each treatment arm, respectively.

DAS28 calculated from SJC and TJC using the 28 joints count, the serological markers of inflammation (ESR \[millimeter per hour\] or CRP \[milligram per liter\]) and patient's general health assessment (recorded on a VAS scale of 0 mm-100 mm). DAS28 \<=1.6 = remission, DAS28 \<=2.4 = low disease activity, DAS28 \>=3.2 to 5.1 = moderate disease activity, DAS28 \>5.1 = severe disease activity.

Outcome measures

Outcome measures
Measure	Etanercept n=3118 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=1356 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 Change at Year 1 (n= 3118, 1356)	-2.16 units on a scale Interval -2.21 to -2.11	-1.42 units on a scale Interval -1.51 to -1.33
Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 Change at Year 2 (n= 2536, 1066)	-2.40 units on a scale Interval -2.46 to -2.34	-1.79 units on a scale Interval -1.89 to -1.69
Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 Change at Year 3 (n= 2141, 783)	-2.55 units on a scale Interval -2.62 to -2.49	-1.95 units on a scale Interval -2.07 to -1.83
Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 Change at Year 4 (n= 1623, 534)	-2.16 units on a scale Interval -2.21 to -2.11	-1.42 units on a scale Interval -1.51 to -1.33
Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 Change at Year 5 (n= 1351, 415)	-2.71 units on a scale Interval -2.79 to -2.63	-2.47 units on a scale Interval -2.62 to -2.31

SECONDARY outcome

Timeframe: Year 1, 2, 3, 4, 5

Outcome measures

Outcome measures
Measure	Etanercept n=3118 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=1356 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Remission: Year 1 (n= 3118, 1356)	13.0 percentage of participants	12.6 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Remission: Year 2 (n= 2536, 1066)	17.0 percentage of participants	16.2 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Remission: Year 3 (n= 2141, 783)	20.1 percentage of participants	21.3 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Remission: Year 4 (n= 1623, 534)	23.7 percentage of participants	20.0 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Remission: Year 5 (n= 1351, 415)	23.4 percentage of participants	25.1 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Low disease activity: Year 1 (n= 3118, 1356)	24.1 percentage of participants	22.0 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Low disease activity: Year 2 (n= 2536, 1066)	30.5 percentage of participants	28.8 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Low disease activity: Year 3 (n= 2141, 783)	34.1 percentage of participants	33.2 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Low disease activity: Year 4 (n= 1623, 534)	37.6 percentage of participants	35.0 percentage of participants
Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) Low disease activity: Year 5 (n= 1351, 415)	37.3 percentage of participants	43.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Time to Remission	NA years Median time to remission could not be calculated as fewer than 50% of participants had achieved remission during the follow up period.	NA years Median time to remission could not be calculated as fewer than 50% of participants had achieved remission during the follow up period.

SECONDARY outcome

Timeframe: Baseline

HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.

Outcome measures

Outcome measures
Measure	Etanercept n=3529 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Health Assessment Questionnaire (HAQ) Score at Baseline	2.1 units on a scale Standard Deviation 0.5	1.7 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline, Year 1, 2, 3

Outcome measures

Outcome measures
Measure	Etanercept n=2291 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=1545 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Year 1, 2, and 3 Change at Year 1 (n= 2291, 1545)	-0.317 units on a scale Interval -0.339 to -0.296	-0.057 units on a scale Interval -0.084 to -0.03
Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Year 1, 2, and 3 Change at Year 2 (n= 2071, 1203)	-0.309 units on a scale Interval -0.333 to -0.286	-0.062 units on a scale Interval -0.095 to -0.03
Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Year 1, 2, and 3 Change at Year 3 (n= 1947, 995)	-0.301 units on a scale Interval -0.326 to -0.277	-0.064 units on a scale Interval -0.1 to -0.027

SECONDARY outcome

Timeframe: Year 1, 2, 3

HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3. Participants who had HAQ total score \<=0.5 were considered in remission state.

Outcome measures

Outcome measures
Measure	Etanercept n=2291 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=1545 Participants Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Percentage of Participants With Remission Based on Health Assessment Questionnaire (HAQ) Score Year 1 (n = 2291, 1545)	24.9 percentage of participants	8.4 percentage of participants
Percentage of Participants With Remission Based on Health Assessment Questionnaire (HAQ) Score Year 2 (n = 2071, 1203)	23.6 percentage of participants	8.0 percentage of participants
Percentage of Participants With Remission Based on Health Assessment Questionnaire (HAQ) Score Year 3 (n = 1947, 995)	23.9 percentage of participants	7.2 percentage of participants

SECONDARY outcome

Timeframe: 6 months prior to and 6 months post switching etanercept

Population: FAS population. Here "N" (number of participants analyzed): participants evaluable for this measure, "n": participants evaluable for specified time-points. Only participants treated with ETN were to be analyzed for this outcome measure.

Outcome measures

Outcome measures
Measure	Etanercept n=1227 Participants Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
Health Assessment Questionnaire (HAQ) Score 6 Months Prior to And 6 Months Post-Switching Etanercept 6-Months Prior to Switching (n = 1227)	2.006 units on a scale Standard Deviation 0.625	—
Health Assessment Questionnaire (HAQ) Score 6 Months Prior to And 6 Months Post-Switching Etanercept 6-Months Post-Switching (n = 754)	2.017 units on a scale Standard Deviation 0.641	—

Adverse Events

Etanercept

Serious events: 944 serious events

Other events: 0 other events

Deaths: 0 deaths

nbDMARDs

Serious events: 744 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Etanercept n=3529 participants at risk Participants with active rheumatoid arthritis (RA) who received etanercept (ETN, as their first biological drug) in doses as per approved product label or summary of product characteristics (SmPC) were observed using the data in British Society for Rheumatology Biologics Register (BSRBR) for a maximum of 10 years. Doses of ETN and any concomitant medication could be adjusted according to medical and therapeutic necessity. Participants were eligible to receive any other therapy instead of ETN, as per investigator's discretion and the doses of these were not controlled in the follow-up.	nbDMARDs n=2864 participants at risk Biological naive participants with active RA who received non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) in doses as per approved product label or SmPC were observed using the data in BSRBR for a maximum of 8.75 years. Doses of nbDMARDs and any concomitant medication could be adjusted according to medical and therapeutic necessity.
General disorders Death	5.8% 203/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	7.8% 223/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative	0.51% 18/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	1.0% 29/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Infections and infestations Pneumonia	5.8% 205/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	7.9% 225/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Infections and infestations Septicaemia	0.96% 34/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.98% 28/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Infections and infestations Bone/Joint infection	2.4% 83/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	1.1% 31/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Infections and infestations Other serious infection	8.9% 314/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	6.0% 171/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.31% 11/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.63% 18/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloma	0.03% 1/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.14% 4/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.17% 6/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.24% 7/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-melanoma skin cancer	2.2% 79/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	2.8% 79/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Solid tumours	4.3% 153/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	5.5% 158/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Cardiac disorders Congestive heart failure	0.79% 28/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	1.3% 36/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Cardiac disorders Myocardial infarction	1.8% 65/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	2.4% 69/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Cardiac disorders Other Cardiac events	2.4% 85/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	3.6% 102/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Nervous system disorders Central demyelination	0.03% 1/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.03% 1/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Nervous system disorders Optic neuritis	0.06% 2/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.00% 0/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Nervous system disorders Peripheral Neuropathy	0.28% 10/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.42% 12/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Nervous system disorders Other CNS event	3.3% 117/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	3.0% 85/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Aplastic anaemia	0.03% 1/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.00% 0/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Pancytopaenia	0.11% 4/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.28% 8/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Agranulocytosis	0.06% 2/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.00% 0/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Other dyscrasia	1.4% 51/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	1.9% 53/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Leukopaenia	0.20% 7/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.07% 2/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.
Blood and lymphatic system disorders Pulmonary fibrosis	0.40% 14/3529 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.	0.45% 13/2864 Due to retrospective nature of the study, it was difficult to capture non serious adverse events (Non-SAEs) and only serious adverse events (SAEs) were captured.