Table 2.
Enthesitis resolution/improvementa through week 52 in patients with enthesitis at baseline and clinical responsea through week 52 in PsA patients with or without enthesitis at baseline
| Outcome | Patients with enthesitis (LEI EC ≥1) |
Patients without enthesitis (LEI EC = 0) |
|||||
|---|---|---|---|---|---|---|---|
| Guselkumab 100 mg |
Placebo (wks 0–24)→Q4W (wks 24–52) | Guselkumab 100 mg |
Placebo (wks 0–24)→Q4W (wks 24–52) | ||||
| Week | Q4W | Q8W | Q4W | Q8W | |||
| Randomized, treated pts, n | 243 | 230 | 255 | 130 | 144 | 116 | |
| Enthesitis resolution (LEI = 0), % (95% CI)b; adjusted P-value vs placeboc | 24 | 44.9 (38.4, 51.3); 0.0301 | 49.6 (42.9, 56.2); 0.0301 | 29.4 (23.6, 35.2) | — | — | — |
| 52 | 57.6 (51.2, 64.4) | 57.8 (51.2, 64.4) | 61.6 (55.4, 67.7) | — | — | — | |
| Randomized, treated pts with evaluable data at week 52, n | 237 | 225 | 251 | — | — | — | |
| 24 | −1.6 (−1.8, −1.4) | −1.5 (−1.7, −1.3) | −1.0 (−1.2, −0.8) | — | — | — | |
| 52 | −1.8 (−2.0, −1.6) | −1.8 (−2.0, −1.6) | −1.8 (−2.0, −1.7) | — | — | — | |
| Clinical outcomes in randomized, treated pts, n | 243 | 230 | 255 | 130 | 144 | 116 | |
| ACR20, % (95% CI)b | 24 | 61.3 (55.0, 67.6) | 59.6 (53.0, 66.1) | 29.8 (24.0, 35.6) | 63.8 (55.2, 72.5) | 60.4 (52.1, 68.8) | 27.6 (19.0, 36.2) |
| 52 | 72.4 (66.6, 78.3) | 68.3 (62.0, 74.5) | 58.0 (51.8, 64.3) | 70.0 (61.7, 78.3) | 71.5 (63.8, 79.2) | 69.0 (60.1, 77.8) | |
| ACR50, % (95% CI)b | 24 | 31.3 (25.2, 37.3) | 27.4 (21.4, 33.4) | 13.3 (9.0, 17.7) | 39.2 (30.5, 48.0) | 36.8 (28.6, 45.0) | 10.3 (4.4, 16.3) |
| 52 | 46.9 (40.4, 53.4) | 42.6 (36.0, 49.2) | 33.3 (27.4, 39.3) | 51.5 (42.6, 60.5) | 49.3 (40.8, 57.8) | 45.7 (36.2, 55.2) | |
| ACR70, % (95% CI)b | 24 | 11.1 (7.0, 15.3) | 11.7 (7.4, 16.1) | 5.1 (2.2, 8.0) | 23.8 (16.1, 31.6) | 23.6 (16.3, 30.9) | 3.4 (0.0, 7.2) |
| 52 | 24.7 (19.1, 30.3) | 25.7 (19.8, 31.5) | 15.7 (11.0, 20.3) | 31.5 (23.2, 39.9) | 29.9 (22.0, 37.7) | 20.7 (12.9, 28.5) | |
| DAS28-CRP, LS mean (95% CI)b change from baselined | 24 | −1.6 (−1.8, −1.5) | −1.5 (−1.7, −1.4) | −0.9 (−1.1, −0.8) | −1.5 (−1.7, −1.3) | −1.5 (−1.7, −1.3) | −0.8 (−1.0, −0.6) |
| 52 | −2.0 (−2.2, −1.9) | −1.9 (−2.1, −1.8) | −1.8 (−2.0, −1.7) | −1.9 (−2.1, −1.7) | −1.9 (−2.1, −1.6) | −1.8 (−2.0, −1.6) | |
| 24 | −0.4 (−0.4, −0.3) | −0.4 (−0.4, −0.3) | −0.1 (−0.2, 0.0) | −0.4 (−0.5, −0.3) | −0.3 (−0.4, −0.2) | −0.1 (−0.2, −0.0) | |
| 52 | −0.5 (−0 6, −0.4) | −0.4 (−0.5, −0.4) | −0.3 (−0.4, −0.2) | −0.5 (−0.6, −0.4) | −0.4 (−0.5, −0.3) | −0.3 (−0.4, −0.3) | |
| 24 | 6.7 (5.8, 7.7) | 7.0 (6.0, 7.9) | 3.3 (2.4, 4.2) | 6.9 (5.6, 8.2) | 6.4 (5.1, 7.7) | 1.9 (0.5, 3.4) | |
| 52 | 8.5 (7.4, 9.6) | 8.1 (7.0, 9.2) | 6.9 (5.8, 7.9) | 8.1 (6.6, 9.5) | 7.4 (5.9, 8.8) | 6.2 (4.6, 7.8) | |
| SF-36 MCS, LS mean (95% CI)b change from baselined | 24 | 4.1 (3.0, 5.2) | 4.1 (2.9, 5.2) | 1.8 (0.7, 2.9) | 3.5 (2.0, 4.9) | 3.3 (1.9, 4.7) | 2.6 (1.1, 4.2) |
| 52 | 4.7 (3.6, 5.8) | 5.0 (3.9, 6.1) | 4.0 (2.9, 5.0) | 3.8 (2.3, 5.2) | 3.4 (2.0, 4.8) | 4.3 (2.7, 5.8) | |
| MDA, % (95% CI)b | 24 | 16.9 (12.0, 21.8) | 19.1 (13.8, 24.4) | 7.1 (3.7, 10.4) | 33.8 (25.3, 42.4) | 32.6 (24.6, 40.6) | 9.5 (3.7, 15.2) |
| 52 | 30.9 (24.9, 36.9) | 26.5 (20.6, 32.4) | 23.5 (18.1, 28.9) | 45.4 (36.4, 54.3) | 37.5 (29.2, 45.8) | 37.9 (28.7, 47.2) | |
| Skin responses in randomized, treated pts with ≥3% BSA psoriasis and IGA ≥2 at baseline, n | 187 | 162 | 182 | 86 | 96 | 79 | |
| IGA 0/1, % (95% CI)b | 24 | 71.1 (64.4, 77.9) | 64.8 (57.2, 72.5) | 17.6 (11.8, 23.4) | 69.8 (59.5, 80.1) | 68.8 (59.0, 78.5) | 19.0 (9.7, 28.3) |
| 52 | 80.2 (74.2, 86.2) | 71.6 (64.4, 78.9) | 76.4 (69.9, 82.8) | 80.2 (71.2, 89.2) | 69.8 (60.1, 79.5) | 74.7 (64.5, 84.9) | |
| PASI75, % (95% CI)b | 24 | 81.8 (76.0, 87.6) | 77.2 (70.4, 83.9) | 18.7 (12.7, 24.6) | 79.1 (69.9, 88.2) | 79.2 (70.5, 87.8) | 24.1 (14.0, 34.1) |
| 52 | 89.3 (84.6, 94.0) | 81.5 (75.2, 87.8) | 81.9 (76.0, 87.7) | 87.2 (79.6, 94.8) | 82.3 (74.1, 90.4) | 74.7 (64.5, 84.9) | |
| PASI90, % (95% CI)b | 24 | 62.6 (55.4, 69.8) | 61.7 (53.9, 69.5) | 8.8 (4.4, 13.2) | 59.3 (48.3, 70.3) | 64.6 (54.5, 74.7) | 13.9 (5.7, 22.2) |
| 52 | 77.0 (70.7, 83.3) | 71.0 (63.7, 78.3) | 69.2 (62.3, 76.2) | 74.4 (64.6, 84.2) | 68.8 (59.0, 78.5) | 68.4 (57.5, 79.2) | |
| PASI100, % (95% CI)b | 24 | 44.4 (37.0, 51.8) | 35.8 (28.1, 43.5) | 2.2 (0.0, 4.6) | 45.3 (34.2, 56.5) | 44.8 (34.3, 55.3) | 7.6 (1.1, 14.1) |
| 52 | 57.8 (50.4, 65.1) | 48.1 (40.1, 56.2) | 49.5 (41.9, 57.0) | 64.0 (53.2, 74.7) | 53.1 (42.6, 63.6) | 58.2 (46.7, 69.7) | |
Results are pooled across DISCOVER-1 and DISCOVER-2.
Patients meeting treatment failure criteria and with missing dichotomous end point data were considered non-responders. Continuous end point data missing following discontinuation or for other reasons were imputed as no change from baseline or using MI (assumed to be missing-at-random), respectively. Patients who received placebo only before discontinuing treatment had missing data imputed as non-response or no improvement through week 52.
95% confidence intervals based on the Wald statistic.
P-value adjusted for multiplicity [18]. Treatment difference assessed via a Cochran–Mantel–Haenszel test.
LS mean determined using an analysis of covariance model.
ACR20/50/70: ≥20/50/70% improvement per ACR response criteria; BSA: body surface area; EC: enthesitis count; IGA 0/1: Investigator’s Global Assessment of psoriasis score of 0 or 1 and ≥ 2-point reduction from baseline; LEI: Leeds Enthesitis Index; LS: least squares; MDA: Minimal Disease Activity; MI: multiple imputation; PASI75/90/100: ≥75/90/100% improvement in the Psoriasis Area and Severity Index; pts: patients; Q4/8W: every 4/8 weeks; SF-36 PCS/MCS: 36-item short form health survey physical/mental component summary; wk: week.