ACR 70 response at 3 years⁹

Three-year ACR 70 nonresponder imputation (NRI) methodology^{3, 9}

‡At 3 years, the intent-to-treat (ITT) population differs between last-observation-carried-forward (LOCF) and NRI analyses due to the exclusion of patients enrolled at sites that were closed prior to year 3. Patients remaining in the study at the time of site closure were excluded from the NRI analysis.

TEMPO = Trial of Etanercept and MTX with Radiographic Outcomes.

Please see TEMPO study design.

Patients who achieved DAS 44 clinical remission at 3 years⁴

Please see TEMPO study design.

Modified Total Sharp Scores at 3 years⁹

Per protocol, in order to read the year 3 data, the years 1 and 2 data were reread. Because of the known variability in reading of the radiographic images in RA, all radiographs were reread, blinded to patient and time point, by the two physicians who read the images for the year 2 report. Thus, the year 3 scoring of the radiographic images is considered a new reading of the years 1 and 2 time points.⁹

Please see TEMPO study design.

Modified TSS at 1 year^9*

*Modified Total Sharp Score is based on the Sharp/van der Heijde method (0 = no damage). All radiographic data based on ITT analysis of patients with an acceptable baseline and post baseline radiograph. Linear extrapolation methodology was used.

Please see COMET study design.

Joint erosion and joint space narrowing scores at 1 year^9*

• Joint space narrowing is applied to the hands and feet and based on a scale of 0 to 4⁹
• Joint erosion scores are measured per joint and range from 0 to 5 (for the hands) and 0 to 10 (for the feet)⁹

*The combined scores of joint erosions and joint space narrowings are the basis of the modified TSS.⁹

All radiographic data based on ITT analysis of patients with an acceptable baseline and postbaseline radiograph. Linear extrapolation methodology was used.⁹

Please see COMET study design.

ACR 70 response at 1 year^9*

1-year ACR 70 NRI methodology⁹

*The modified ITT (mITT) efficacy population included all subjects who received at least one dose of drug and reported both baseline and postbaseline DAS 28 results. The mITT populations for the ENBREL + MTX combination therapy and MTX monotherapy groups were 265 and 263, respectively. The mITT populations for ACR 70 response were smaller because some patients did not have complete data. Patients were not included in the ACR or DAS analyses unless they had at least one postbaseline ACR or DAS value.

Please see COMET study design.

DAS 44 clinical remission at 1 year^9*

• DAS 44 clinical remission was seen as early as 4 weeks (11% ENBREL + MTX [n=264] vs 2% MTX [n=262], P < 0.001)⁹
• DAS 28 clinical remission at 1 year: 50% ENBREL + MTX vs 28% MTX, P < 0.001.⁹
  • DAS 28 clinical remission was seen as early as 2 weeks: 5% ENBREL + MTX [n=258] vs 0.4% MTX [n=252], P = 0.002⁹

*DAS 44 clinical remission is defined as a DAS <1.6 units. Calculation of DAS 44 utilizes tenderness scores (Ritchie Articular Index), swollen joint count, ESR, and VAS from a patient’s general health assessment. The DAS 44 is a validated tool used in clinical trialsand serves as the basis for the EULAR response criteria.¹⁴

In this study, a modified DAS, DAS 28, was also utilized based on the 28-joint count (tender28 and swollen28) rather than 44 joints. Clinical remission is defined as DAS 28 < 2.6 units.¹⁴

Please see COMET study design.

Patients with DAS 28 painful joint count of zero (LOCF)⁹

Patients with DAS 28 swollen joint count of zero (LOCF)⁹

• Swollen joint counts and painful joint counts were prorated to a full count of 69 (swollen joints) or 71 (painful joints) before analysis in order to adjust for missing joint assessments⁹

Please see COMET study design.

Percent of patients who achieved a HAQ Disability Index (DI)* score of ≤ 0.50)⁹

• The Health Assessment Questionnaire Disability Index (HAQ-DI) is designed to assess patient outcomes in the following 8 areas: dressing, walking, grip, arising, hygiene, common activities, eating, and reach.

*The HAQ-DI is scored on a scale of 0 to 3 units. A HAQ-DI score of 0 indicates the lack of any measurable degree of disability, whereas a score of 3 means that a patient is unable to perform all activities.¹⁵

At week 52, the HAQ-DI response populations were smaller (than DAS 28) as some patients did not have complete data. Patients were not included in the HAQ-DI analysis unless they had at least one postbaseline value.^9,15

Please see COMET study design.

Measures of disease activity at 1 year⁹

TSS = Total Sharp Score; ACR = American College of Rheumatology; DAS = Disease Activity Score, HAQ = Health Assessment Questionnaire. For further definitions of the efficacy measurements, please see each specific graph in the pull–downs featured above.

ACR responses at 12 and 24 weeks^9*

ACR 20/50/70 NRI methodology at 12 and 24 weeks^9*

• In clinical trials, responses (ACR 20) generally appeared within 2 weeks of therapy, and nearly always occurred by 3 months³
• The incremental response of patients was analyzed at weeks 12 and 24⁹

*The modified ITT (mITT) efficacy population included all subjects who received at least one dose of drug and reported both baseline and postbaseline DAS 28 results. The mITT populations for the ENBREL + MTX combination therapy and MTX monotherapy groups were 265 and 263, respectively. The mITT populations for ACR 70 response were smaller because some patients did not have complete data. Patients were not included in the ACR or DAS analyses unless they had at least one postbaseline ACR or DAS value.

Please see COMET study design.

DAS 44 clinical remission at 12 and 24 weeks^9*

• DAS 44 clinical remission was seen as early as 4 weeks (11% ENBREL + MTX [n=264] vs 2% MTX [n=262], P < 0.001)⁹
• DAS 28 clinical remission at 1 year: 50% ENBREL + MTX vs 28% MTX, P < 0.001.⁹
  • DAS 28 clinical remission was seen as early as 2 weeks: 5% ENBREL + MTX [n=258] vs 0.4% MTX [n=252]. P = 0.002⁹

*DAS 44 clinical remission is defined as a DAS <1.6 units. Calculation of DAS 44 utilizes tenderness scores (Ritchie Articular Index), swollen joint count, ESR, and VAS from a patient general health assessment. The DAS 44 is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.

In this study, a modified DAS, DAS 28, was also utilized based on the 28-joint count (tender28 and swollen28) rather than 44 joints. Clinical remission is defined as DAS 28<2.6 units.¹³

Please see COMET study design.

Patients with DAS 28 painful joint count of zero^9*

Patients with DAS 28 swollen joint count of zero⁹

Please see COMET study design.

DAS 44 clinical response and radiographic outcomes⁹

• In clinical trials, responses (ACR 20) generally appeared within 2 weeks after initiation of therapy and nearly always occurred by 3 months³
• Not all DAS 44 partial responders at week 12 had radiographic data available at week 52.

No radiographic progression=TSS change ≤ 0.0.

*Partial responders were defined as patients who achieved a DAS 44 low or moderate disease activity and achieved at least an ACR 20 response at 12 weeks.
†Increased response = decreased disease activity by at least one level (moderate disease ⇒ low disease activity or clinical remission, low disease activity ⇒ clinical remission).
‡Maintained response = maintained level of disease activity (moderate disease activity ⇒ moderate disease activity, low disease activity ⇒ low disease activity).
§Decreased response = increase in disease activity by at least one level (moderate disease activity ⇒ high disease activity, low disease activity ⇒ moderate or high disease activity).

Please see COMET study design.