TABLE 1.
Baseline, demographic and steroid response characteristics in seven GSK-sponsored clinical studies
| Clinical Studies | |||||||
|---|---|---|---|---|---|---|---|
| FFA109684 | FFA109685 | FFA109687 | FFA112059 | HZA106827 | HZA106829 | HZA106837 | |
| Clinical Phase | PIIb | PIIb | PIIb | PIIIa | PIIIa | PIIIa | PIIIa |
| N | 255 | 225 | 259 | 143 | 142 | 284 | 616 |
| Age (years) | 48.5 ± 13 | 42.1 ± 17.3 | 41.3 ± 15.9 | 42.4 ± 16.1 | 42.4 ± 16.0 | 47.3 ± 13.7 | 43.9 ± 16.5 |
| Age of Onset (Years) | 29.9 ± 17.9 | 25.0 ± 18.8 | 25.7 ± 18.5 | 25.3 ± 16.9 | 30.6 ± 18.5 | 33.6 ± 17.5 | 29.6 ± 18.1 |
| FEV1 at baseline (L) | 2.3 ± 0.6 | 2.4 ± 0.6 | 2.4 ± 0.7 | 2.4 ± 0.7 | 2.3 ± 0.6 | 2.2 ± 0.7 | 2.3 ± 0.7 |
| FEV1 at baseline (% of predicted) | 68.8 ± 11.5 | 73.7 ± 11.1 | 70.9 ± 12.2 | 72.5 ± 11.9 | 69.1 ± 10.4 | 66.3 ± 11.8 | 71.9 ± 10.5 |
| Run-In period | 28 day | 28 day | 28 day | 4 weeks | 4 weeks | 4 weeks | 2 weeks |
| Treatment on Run-In | ICS | ICS | non-CS | ICS | Asthma controller | ICS | FP or ICS |
| Sex (% female) | 56.5 | 59.6 | 58.7 | 55.9 | 63.4 | 59.5 | 66.2 |
| Height (cm) | 168.7 ± 9.5 | 168.3 ± 9.6 | 168.6 ± 10.1 | 168.8 ± 10.4 | 167.6 ± 9.0 | 167.9 ± 9.9 | 166.2 ± 9.7 |
| FF subject numbers | 199 | 182 | 210 | 71 | 142 | 142 | 616 |
| FF dose(s) mcg QD | 200, 400, 600, 800 | 100, 200, 300, 400 | 25, 50, 100, 200 | 100 | 100 | 200 | 100 |
| FP subject numbers | 56 | 43 | 49 | 72 | NA | 142 | NA |
| FP dose(s) mcg BD | 500 | 250 | 100 | 250 | NA | 500 | NA |
| Change FEV1 * | 0.18 ± 0.35 | 0.20 ± 0.42 | 0.29 ± 0.40 | 0.15 ± 0.36 | 0.33 ± 0.46 | 0.20 ± 0.44 | 0.19 ± 0.39 |
| ANCOVA Parameter Estimate** | 0.000 ± 0.030 | −0.017 ± 0.036 | −0.018 ± 0.033 | −0.034 ± 0.043 | 0.008 ± 0.050 | −0.007 ± 0.035 | −0.031 ± 0.022 |
| ANCOVA Estimate P value | 1.00 | 0.64 | 0.57 | 0.43 | 0.87 | 0.85 | 0.16 |
| GG to GA/AA Odds Ratio† | 1.62 | 1.24 | 1.61 | 4.00 | 0.63 | 1.08 | 1.33 |
| 95% confidence interval | 0.62–4.42 | 0.50–3.10 | 0.62–4.41 | 1.22–15.7 | 0.20–1.87 | 0.51–2.29 | 0.73–2.48 |
| P value | 0.33 | 0.65 | 0.33 | 0.02 | 0.40 | 0.85 | 0.35 |
*
FEV1 change was calculated as the pre-dose FEV1 measurement taken during at the clinic visit while still on-treatment minus the pre-dose FEV1 measurement taken on the first day of treatment
**
Analysis of covariance estimate of the rs37973 per-allele effect for each copy of the “G” allele, ± the standard error of the estimate. Model included five clinical covariates in addition to rs37973 coded as 0, 1, or 2.
†
Ratio of the odds of being in the lowest quartile of response (defined as change in FEV1, adjusted for five clinical covariates) given genotype GG relative to the odds given genotype GA or AA.