Table 2.
Primary and key secondary efficacy outcomes during the placebo-controlled period*
| FIL200 (n=475) |
FIL100 (n=480) |
ADA (n=325) |
PBO (n=475) |
|
| Primary outcome | ||||
| ACR20, week 12 | ||||
| n/N | 364/475 | 335/480 | 229/325 | 237/475 |
| % (95% CI) | 76.6 (72.7 to 80.5) | 69.8 (65.6 to 74.0) | 70.5 (65.3 to 75.6) | 49.9 (45.3 to 54.5) |
| Difference vs PBO (95% CI)† | 26.7 (20.6 to 32.8) | 19.9 (13.6 to 26.2) | 20.6 (13.6 to 27.5) | |
| P value vs placebo | <0.001 | <0.001 | <0.001‡ | |
| Key secondary outcomes with hierarchical testing | ||||
| HAQ-DI change from baseline to week 12 | ||||
| N | 457 | 459 | 311 | 435 |
| Mean±SD | −0.69±0.61 | −0.56±0.56 | −0.61±0.56 | −0.42±0.54 |
| Difference vs PBO (95% CI)† | −0.29 (−0.36 to −0.22) | −0.17 (−0.24 to −0.10) | −0.20 (−0.28 to −0.13) | |
| P value vs PBO | <0.001 | <0.001 | <0.001‡ | |
| DAS28(CRP) <2.6, week 12 | ||||
| n/N | 162/475 | 114/480 | 77/325 | 44/475 |
| % (95% CI) | 34.1 (29.7 to 38.5) | 23.8 (19.8 to 27.7) | 23.7 (18.9 to 28.5) | 9.3 (6.6 to 12.0) |
| Difference vs PBO (95% CI)† | 24.8 (19.6 to 30.0) | 14.5 (9.7 to 19.3) | 14.4 (8.9 to 20.0) | |
| P value vs PBO | <0.001 | <0.001 | <0.001‡ | |
| mTSS change from baseline to week 24 | ||||
| N | 405 | 404 | 271 | 351 |
| Mean±SD | 0.13±0.9 | 0.17±0.91 | 0.16±0.95 | 0.37±1.42 |
| Difference vs PBO (95% CI)† | −0.27 (−0.43 to −0.12) | −0.25 (−0.40 to −0.10) | −0.22 (−0.39 to −0.05) | |
| P value vs PBO | <0.001 | 0.001 | 0.012‡ | |
| Non-inferiority DAS28(CRP) ≤3.2, week 12 | ||||
| n/N | 236/475 | 186/480 | 141/325 | 111/475 |
| % (95% CI) | 49.7 (45.1 to 54.3) | 38.8 (34.3 to 43.2) | 43.4 (37.8 to 48.9) | 23.4 (19.5 to 27.3) |
| P value vs ADA | <0.001 | 0.054 | ||
| Key secondary outcomes without multiplicity adjustment | ||||
| SF-36 PCS change from baseline to week 12 | ||||
| N | 459 | 463 | 310 | 440 |
| Mean±SD | 9.2±8.1 | 8.5±7.7 | 8.4±7.9 | 5.8±7.1 |
| Difference vs PBO (95% CI)† | 3.7 (2.8 to 4.6) | 3.1 (2.2 to 4.0) | 2.6 (1.6 to 3.6) | |
| Exploratory p value vs PBO | <0.001 | <0.001 | <0.001 | |
| FACIT-F change from baseline to week 12 | ||||
| N | 452 | 455 | 304 | 432 |
| Mean±SD | 9.2±9.8 | 9.1±10.2 | 8.8±9.2 | 6.8±9.9 |
| Difference vs PBO (95% CI)† | 2.8 (1.7 to 3.9) | 2.6 (1.5 to 3.7) | 2.1 (0.9 to 3.3) | |
| Exploratory p value vs PBO | <0.001 | <0.001 | <0.001 | |
| Superiority DAS28(CRP) ≤3.2, week 12 | ||||
| Difference vs ADA (95% CI)† | 6.3 (−1.0 to 13.6) | −4.6 (−11.8 to 2.6) | ||
| Exploratory p value vs ADA | 0.069 | 0.18 | ||
| Non-inferiority DAS28(CRP) <2.6, week 12 | ||||
| Exploratory p value vs ADA | <0.001 | 0.002 | ||
| Superiority DAS28(CRP) <2.6, week 12 | ||||
| Difference vs ADA (95% CI)† | 10.4 (3.9 to 17.0) | 0.1 (−6.2 to 6.3) | ||
| Exploratory p value vs ADA | 0.001 | 0.99 | ||
*Hierarchical testing according to prespecified, US Food and Drug Administration-reviewed, statistical analysis plan. Patients who had missing values were defined as non-responders, and NRI was employed for both primary and key secondary analyses.
†Difference in response rates vs placebo or ADA for categorical outcomes; least-squares mean difference vs placebo or ADA for continuous outcomes.
‡Exploratory p value without multiplicity adjustment.
ACR20, American College of Rheumatology criteria 20% decrease from baseline; ADA, adalimumab; DAS28(CRP), Disease Activity Score in 28 joints with C reactive protein; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; HAQ-DI, Health Assessment Questionnaire-Disability Index; mTSS, van der Heijde modified total Sharp score; NRI, non-responder imputation; PBO, placebo; SF-36 PCS, Short Form 36 Physical Component Summary.