6 was 0.6 (from 1.6 to 1.0)for the 25 mg etanercept group and 0 (from 1.7 to 1.7) for the placebo group. In Study II, the mean improvement frombaseline to month 6 was 0.6 (from 1.5 to 0.9) for the etanercept/MTX group and 0.2 (from 1.3 to 1.2) for theplacebo/MTX group. In Study III, the mean improvement in the HAQ score from baseline to month 6 was 0.7 (from1.5 to 0.7) for 25 mg etanercept twice weekly. All subdomains of the HAQ in Studies I and III were improved inpatients treated with etanercept.
In Study III, patients treated with 25 mg etanercept twice weekly showed greater improvement from baseline in SF-36physical component summary score compared to etanercept 10 mg twice weekly and no worsening in the SF-36mental component summary score. In open-label etanercept studies, improvements in physical function and disabilitymeasures have been maintained for up to 4 years.
In Study IV, median HAQ scores improved from baseline levels of 1.8, 1.8, and 1.8 to 1.1, 1.0, and 0.6 at 12 monthsin the MTX, etanercept, and etanercept/MTX combination treatment groups, respectively (combination versus bothMTX and etanercept, p < 0.01). Twenty-nine percent of patients in the MTX alone treatment group had animprovement of HAQ of at least 1 unit versus 40% and 51% in the etanercept alone and the etanercept/MTXcombination treatment groups, respectively.
Radiographic Response
In Study III, structural joint damage was assessed radiographically and expressed as change in Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing (JSN) score. Radiographs of hands/wrists and
forefeet were obtained at baseline, 6 months, 12 months, and 24 months and scored by readers who were unaware oftreatment group. The results are shown in Table 9. A significant difference for change in erosion score was observedat 6 months and maintained at 12 months.
Table 9. Mean Radiographic Change Over 6 and 12 Months in Study III
MTX
25 mg
Etanercept
MTX/Etanercept
(95% Confidence Interval
*
) P Value
12
Months
6 Months
Total Sharp
Score 1.59 1.00 0.59 (-0.12, 1.30)
Erosion Score 1.03 0.47 0.56 (0.11, 1.00)
JSN Score 0.56 0.52 0.04 (-0.39, 0.46)
Total Sharp
Score
1.06 0.57 0.49 (0.06, 0.91)
Erosion Score 0.68 0.30 0.38 (0.09, 0.66)
JSN Score 0.38 0.27 0.11 (-0.14, 0.35)
0.1
0.002
0.5
0.001
0.001
0.6
* 95% confidence intervals for the differences in change scores between MTX and etanercept.
Patients continued on the therapy to which they were randomized for the second year of Study III. Seventy-twopercent of patients had x-rays obtained at 24 months. Compared to the patients in the MTX group, greater inhibitionof progression in TSS and erosion score was seen in the 25 mg etanercept group, and, in addition, less progressionwas noted in the JSN score.
In the open-label extension of Study III, 48% of the original patients treated with 25 mg etanercept have beeneva luated radiographically at 5 years. Patients had continued inhibition of structural damage, as measured by the TSS,and 55% of them had no progression of structural damage. Patients originally treated with MTX had further reductionin radiographic progression once they began treatment with etanercept.
In Study IV, less radiographic progression (TSS) was observed with etanercept in combination with MTX comparedwith etanercept alone or MTX alone at month 12 (Table 10). In the MTX treatment group, 55% of patientsexperienced no radiographic progres |
