Clinical trials and drug discovery
of IS, including biologics. 11 Achievement of LLDAS required all of the following: SLEDAI-2K ≤ 4 without activity in major organ systems, no new features of lupus disease activity, PGA (0–3) ≤ 1, prednisone or equiva- lent ≤ 7.5 mg/day and standard maintenance doses of IS and approved biological agents. 12 BICLA response was defined as all of the following: reduction from baseline of all severe or moderately severe disease activity (ie, BILAG-2004 A to B, C or D, or BILAG-2004 B to C or D) and no worsening in other organ systems (ie, ≥ 1 new A or ≥ 1 new B BILAG-2004 items) and no increase from baseline in SLEDAI-2K score or ≥ 0.3-point increase in PGA. 13 CLASI-50 response was defined as ≥ 50% reduc- tion from baseline in CLASI Activity score and SRI(4) response as at least a 4-point reduction in SLEDAI-2K, no new A or <2 new B BILAG-2004 organ domain scores and a <0.3-point increase in PGA from baseline. 14 In addition, in patients with baseline GC dosage ≥ 10 mg/ day, maintenance of GC reduction was defined by attain- ment of GC (prednisone or equivalent) dosage reduc- tion to ≤ 7.5 mg/day by week 40 and maintenance of GC dosage ≤ 7.5 mg/day from weeks 40 to 52. Safety assessments Safety assessments included AEs, which were coded using the Medical Dictionary for Regulatory Activities, version 22.1. An AE was considered to occur during treatment if it had an onset date on or after the day of the first dose of study treatment and before or on the last dose of study treatment plus 28 days. AEs of special interest (AESI) included non-opportunistic serious infections, opportunistic infections, anaphy- laxis, malignancy, herpes zoster, tuberculosis (including latent tuberculosis), influenza, vasculitis (non-SLE) and major adverse cardiovascular events. Statistical analyses Patient demographics, disease characteristics and SLE- related treatments among IS-inexperienced and -expe- rienced patients at TULIP-1/TULIP-2 baseline were summarised using descriptive statistics. Daily GC doses and changes over time were evaluated using summary statistics of observed data (ie, without any non-responder impu- tation). Response rates and differences in response rates between the anifrolumab and placebo groups for DORIS remission, LLDAS, LLDAS-5, BICLA, CLASI-50, SRI(4) and maintained GC reduction were calculated using a strat- ified Cochran–Mantel–Haenszel approach. Stratification factors for all analyses except for maintained GC reduction at Week 52 were SLEDAI-2K score at screening, Day 1 GC dose, type I interferon gene signature (IFNGS) test result at screening and study (TULIP-1 vs TULIP-2). Stratification factors for maintained GC reduction included SLEDAI-2K score at screening, type I IFNGS test result at screening and study (TULIP-1 vs TULIP-2). In addition to covariates of treatment group and stratification factors, the model for
determining annualised flare rates also included a study-by- treatment interaction factor. For analyses of response rates, patients who discontinued study treatment prematurely were considered non-responders from the visit of discontin- uation onwards. All p values are nominal. Safety analyses included all patients who received at least one dose of study treatment. Safety data were summarised with descriptive statistics. Patient and public involvement No patients and/or members of the public were involved in the design, conduct, reporting or dissemination plans of this research. RESULTS Among patients who received treatment in the TULIP studies, 257 were IS-inexperienced (anifrolumab 300mg, n=127; placebo, n=130) and 469 were IS-experienced (anifrolumab 300mg, n=233; placebo, n=236). Generally, demographics were balanced between IS groups (IS-inexperienced or IS-ex- perienced) at baseline (mean (standard deviation) age 41.9 (11.6) years vs 41.7 (12.1) years; 92.6% vs 93.0%female sex); however, for IS-inexperienced patients versus IS-experienced patients, 15.6% vs 11.5% were Black or African American and 19.5% versus 26.7% were Hispanic or Latino (table 1). Additionally, compared with IS-experienced patients, lower proportions of IS-inexperienced patients were IFNGS-high at screening (78.2% vs 85.1%), had anti-double-stranded DNA positivity (35.4% vs 49.3%), low C4 serum levels (17.9% vs 26.2%)or had a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score ≥ 1 (26.5% vs 37.7%); IS-inexperienced patients also had shorter median disease duration (68.0 vs 94.0 months) (table 1). At baseline, a lower proportion of IS-inexperienced vs IS-experienced patients had a BILAG score ≥ 1 A (41.6% vs 52.5%), while a higher proportion of IS-inexperienced patients had no A and ≥ 2 B (53.3% vs 41.6%). As shown in figure 1A, DORIS remission attain- ment increased from baseline to week 52. At week 52, DORIS remission rates were higher with anifrolumab vs placebo in both IS subgroups (IS-inexperienced, 16.2% (21/127) vs 6.0% (7/130), p=0.0242; IS-experienced, 14.6% (34/233) vs 7.3% (17/236), p=0.0304). LLDAS attainment also increased from baseline to week 52 (figure 1B), and LLDAS response rates at week 52 were numerically higher with anifrolumab versus placebo in both IS subgroups (IS-inexperienced, 34.0% (43/127) vs 26.2% (34/130), p=0.1718; IS-experienced, 27.7% (65/233) vs 16.2% (38/236), p=0.0038). LLDAS-5 response rates at week 52 were numerically higher with anifrolumab vs placebo in both IS subgroups (IS-inexpe- rienced: 27.5% (35/127) vs 22.3% (29/130), p=0.3489; IS-experienced: 23.9% (56/233) vs 13.6% (32/236), p=0.0074) (figure 1C). Compared with placebo, patients treated with anifrolumab were more likely to achieve BICLA response
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Doria A, et al . Lupus Science & Medicine 2026; 13 :e001891. doi:10.1136/lupus-2025-001891
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