Lupus Science & Medicine
(GCs), immunosuppressants (IS) and biologic agents are the main treatment options for SLE. 3 The European Alli- ance of Associations for Rheumatology (EULAR) recom- mendations suggest that the addition of IS and/or biolog- ical agents should be considered in patients with SLE who have an inadequate response to HCQ (alone or in combi- nation with GCs) or in those who are unable to reduce GCs doses below levels acceptable for chronic use. 3 While the efficacy of biologic agents has been established in high-quality randomised controlled trials (RCTs), 3–8 with the exception of mycophenolate, 9 comparable data are lacking for conventional immunosuppressive drugs, with use based largely on clinical experience. 3 EULAR recom- mendations do not classify prior failure of IS as a prereq- uisite for initiation of biologic treatment; however, there are limited data on the clinical benefits of biologics in patients with SLE who have not been treated with IS. In post hoc analyses of the Phase 3 TULIP-1 and TULIP-2 trials of anifrolumab in which patients with SLE were analysed according to the standard therapy they were receiving at baseline, patients who received anifrolumab (300 mg) had consistently higher British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response rates than patients who received placebo, regardless of baseline standard therapy. 10 However, these analyses did not evaluate an effect of prior IS exposure. This post hoc analysis aims to evaluate the efficacy and safety of anifrolumab in patients with moderate- to-severe SLE who, at baseline, had a treatment history of antimalarials and/or oral GCs, but no reported history of IS use. METHODS Full details of the study designs and patient inclusion and exclusion criteria for the randomised, double-blind TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials have been previously described. 4 5 Briefly, the 52-week TULIP trials included patients 18–70 years of age with moderate-to-severe SLE despite standard therapy and investigated treatment with intravenous anifrolumab 150mg (TULIP-2 only), 300 mg or placebo every 4 weeks alongside standard therapy. At screening, eligible patients had an SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥ 6 (excluding points from fever, lupus headache or organic brain syndrome), a clinical SLEDAI-2K ≥ 4 (excluding points from laboratory results), ≥ 1 A or ≥ 2 B BILAG−2004 items and Physician Global Assess- ment (PGA) (scale: 0–3) disease activity ≥ 1. 4 5 During the TULIP-1/TULIP-2 trial period, 4 5 patients with GC dosage ≥ 10 mg/day at baseline were required to attempt tapering to ≤ 7.5mg/day between week 8 and week 40. Stable GC dosages were required from week 40 to week 52 (except for the management of adverse events (AEs)). Patients who received an increase in their GC dose after week 40 were considered non-responders for subse- quent assessments of disease activity. GC tapering was
also encouraged, but not required, in patients who were receiving <10 mg/day GC at baseline. In this post hoc analysis, efficacy and safety outcomes over the 52-week TULIP-1/TULIP-2 period were analysed in patients treated with anifrolumab 300 mg versus placebo alongside standard therapy, comparing IS-experienced patients versus patients without any known prior IS use. Investigators were instructed to report any SLE-specific therapy since time of SLE diagnosis. Patients with no reported IS use since time of SLE diagnosis and no use for at least 12 weeks prior to study consent comprised the ‘IS-inexperienced’ group. The IS-experienced group comprised patients who had a history of IS use (azathioprine, methotrexate, mycophenolate mofetil, mycophenolic acid or mizoribine) prior to TULIP trial enrolment. Patients who had been on IS for at least 8 weeks before entering the trial were required to remain on stable IS during the trial. No patient in either group was allowed to start a new IS during the trial. If a patient started a new IS during the trial, they could remain in the study but were required to discontinue the study treatment and were considered non-responders for efficacy endpoint analyses; for other changes in medication during the study, the restricted medication rules from TULIP-2 were used to determine discontinuation and non-responder status. 5 Efficacy endpoints Attainment of efficacy endpoints over 52 weeks in the TULIP-1/TULIP-2 trials was determined by study treat- ment (intravenous anifrolumab 300 mg vs placebo) among patients characterised as IS-inexperienced or IS-experienced. Efficacy endpoints included achieve- ment of Definition of Remission in SLE (DORIS), Lupus Low Disease Activity State (LLDAS), LLDAS in addition to GC tapering to ≤ 5 mg/day (LLDAS-5), BICLA response, Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)−50 response in patients with baseline CLASI Activity score ≥ 10 and SLE Responder Index (SRI)(4). 4 5 GC use was evaluated in detail: the mean daily GC doses at each timepoint, changes in GC dose from baseline over 52 weeks, and the percentage of patients who achieved GC taper from baseline dose ≥ 10 mg/day to ≤ 7.5 mg/day by week 40 and maintained GC ≤ 7.5 mg/day from week 40 to week 52 were determined. For these endpoints, no use of restricted medications or premature study treatment discontinuation was allowed. Annualised flare rates were also assessed, with a flare defined as either ≥ 1 new BILAG-2004 A or ≥ 2 BILAG-2004 B items compared with the previous visit. Achievement of DORIS required all of the following criteria to be fulfilled: total clinical SLEDAI (sum of all SLEDAI items except for increased DNA binding and low complement) =0, PGA (0–3) <0.5, prednisone/ equivalent dosage ≤ 5 mg/day and stable maintenance
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Doria A, et al . Lupus Science & Medicine 2026; 13 :e001891. doi:10.1136/lupus-2025-001891
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