Primary and secondary outcomes in patients with SLE by IFNGS in pooled data from the TULIP-1 and TULIP-2 trials
| End point | All patients | IFNGS-high | IFNGS-low | ||||||
| Placebo (n=366) | Anifrolumab 300 mg (n=360) | Difference (95% CI), nominal p value* | Placebo (n=302) | Anifrolumab 300 mg (n=298) | Difference (95% CI), nominal p value* | Placebo (n=64) | Anifrolumab 300 mg (n=62) | Difference (95% CI), nominal p value* | |
| n/N (%) | Percentage points | n/N (%) | Percentage points | n/N (%) | Percentage points | ||||
| BICLA response, week 52 | 112/366 (30.8) | 171/360 (47.5) | 16.6 (9.7 to 23.6),<0.001 | 88/302 (29.4) | 142/298 (47.6) | 18.2 (10.5 to 25.8),<0.001 | 24/64 (37.5) | 29/62 (46.8) | 9.3 (–8.0 to 26.5), 0.292 |
| SRI(4) response, week 52 | 147/366 (40.1) | 188/360 (52.2) | 12.1 (4.9 to 19.3),<0.001 | 118/302 (39.0) | 160/298 (53.7) | 14.7 (6.8 to 22.6),<0.001 | 29/64 (45.3) | 28/62 (45.2) | –0.2 (–17.5 to 17.2), 0.986 |
| Sustained GC taper, weeks 40–52† | 59/185 (31.8) | 96/190 (50.5) | 18.7 (8.9 to 28.4),<0.001 | 48/160 (30.1) | 86/168 (51.2) | 21.1 (10.7 to 31.5),<0.001 | 11/25 (43.8) | 10/22 (45.6) | 1.8 (–25.6 to 29.2), 0.897 |
| ≥50% reduction in CLASI-A score, week 12‡ | 24/94 (24.9) | 49/107 (46.0) | 21.0 (8.1 to 34.0), 0.001 | 23/81 (27.9) | 47/93 (50.5) | 22.6 (8.4 to 36.9), 0.002 | 1/13 (8.3) | 2/14 (15.0) | 6.7 (–26.3 to 39.6), 0.692 |
| ≥50% reduction in active (swollen and tender) joints, week 52§ | 71/190 (36.8) | 81/164 (49.4) | 12.6 (2.4 to 22.9), 0.016 | 61/157 (38.4) | 64/129 (49.7) | 11.3 (–0.2 to 22.8), 0.054 | 10/33 (30.4) | 17/35 (48.5) | 18.1 (–5.0 to 41.3), 0.125 |
| Annualised flare rate through week 52¶ | 0.67 | 0.51 | 0.75 (0.60 to 0.95), 0.017 | 0.77 | 0.54 | 0.70 (0.54 to 0.90), 0.005 | 0.49 | 0.55 | 1.12 (0.62 to 2.01), 0.705 |
| FACIT-F response, week 52** | 97/366 (26.5) | 124/360 (34.3) | 7.8 (1.0 to 14.5), NA | 78/302 (25.9) | 102/298 (34.1) | 8.2 (0.8 to 15.6), 0.030 | 19/64 (29.7) | 22/62 (35.5) | 5.8 (–10.7 to 22.3), 0.491 |
| SF-36 MCS response, week 52†† | 75/366 (20.3) | 96/360 (26.5) | 6.1 (−0.1 to 12.4), NA | 57/302 (18.7) | 81/298 (26.9) | 8.2 (1.4 to 15.0), 0.018 | 18/64 (28.1) | 15/62 (24.2) | –3.9 (–19.7 to 11.8), 0.624 |
| SF-36 PCS response, week 52‡‡ | 95/366 (26.1) | 118/360 (32.8) | 6.7 (0.0 to 13.5), NA | 77/302 (25.7) | 98/298 (33.0) | 7.3 (–0.1 to 14.6), 0.053 | 18/64 (28.1) | 20/62 (32.3) | 4.1 (–12.2 to 20.5), 0.620 |
*Percentages of responders, the differences between groups, 95% CIs and nominal p values were calculated using a stratified Cochran-Mantel-Haenszel method with stratification factors SLEDAI-2K score at screening (<10 vs ≥10), GC dosage at week 0 (<10 mg/day vs ≥10 mg/day of prednisone or equivalent) and study. In the overall analysis, IFNGS status at screening (high vs low) was also a stratification factor. Patients treated with restricted medication beyond protocol-allowed thresholds and those who discontinued investigational product were classified as non-responders; between-group differences were calculated in percentage points (the percentage in the anifrolumab group minus the percentage in the placebo group), except as indicated.
†Defined as an oral GC taper to ≤7.5 mg/day from week 40 to week 52 in patients receiving ≥10 mg/day of oral GCs at baseline (prednisone or equivalent).
‡Among patients with baseline CLASI-A score ≥10.
§Among patients with ≥6 swollen and ≥6 tender joints at baseline.
¶Values are annualised flare rates; difference is a rate ratio (with 95% CIs) rather than a percentage point difference. A flare is defined as either ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B items compared with the previous visit.
**FACIT-F response defined as a >3-point improvement from baseline to week 52.
††SF-36 MCS response defined as a >4.6-point improvement from baseline to week 52.
‡‡SF-36 PCS response defined as a >3.4-point improvement from baseline to week 52.
BICLA, BILAG-based Combined Lupus Assessment; BILAG-2004, British Isles Lupus Assessment Group 2004; C, complement; CI, confidence interval; CLASI-A, Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; GC, glucocorticoid; IFNGS, interferon gene signature; MCS, mental component summary; N, number of patients in group; n, number of responders; NA, not available; PCS, physical component summary; SF-36, Short Form 36 Health Survey; SLE, systemic lupus erythematosus; SLEDAI-2K, SLE Disease Activity Index 2000; SRI(4), SLE Responder Index of ≥4.