IMPACT ON DISEASE ACTIVITY

TULIP-1 and TULIP-2 had similar study designs. In TULIP-1, 457 adult patients with moderate to severe SLE were randomized (2:1:2) to SAPHNELO 300 mg IV Q4W (N=180), anifrolumab 150 mg IV Q4W (N=93), or placebo IV Q4W (N=184) in addition to ST at stable doses [either one or any combination of antimalarials (73%), immunosuppressants (47%), nonsteroidal anti-inflammatory agents (18%), and/or OCS (83%)]. OCS (prednisone or equivalent) was tapered per protocol. The primary endpoint was SRI-4 response rate at Week 52 in the SAPHNELO 300 mg group vs the placebo group. Key secondary endpoints were similar. Other prespecified endpoints included BICLA response rate at Week 52.^2,4,8,24

A 3-year, phase 3, randomized, double-blind, placebo-controlled, LTE safety study in adult patients with moderate to severe SLE that completed TULIP-1 or TULIP-2 through the 52-week double-blind treatment period and met all eligibility requirements (N=547). Patients were blinded to treatment and received either SAPHNELO 300 mg or placebo, IV Q4W plus ST. ST included at least one of the following: OCS, antimalarials, nonsteroidal anti-inflammatory agents and immunosuppressants. Investigators could modify background ST treatment, including immunosuppressants and OCS, per clinical judgment. The primary outcome was long-term safety and tolerability as assessed by adverse events (AEs), serious AEs (including deaths), AEs leading to treatment discontinuations (DAEs), and AEs of special interest (AESIs). For primary safety, the main comparison during the 3-year LTE study was between patients who received SAPHNELO 300 mg in the TULIP trials and continued to receive SAPHNELO 300 mg (n=257) and those who received placebo at the start of the TULIP trials and who were re-randomized to receive placebo (n=112). Exploratory efficacy outcomes included SLEDAI-2K, PGA, OCS use, and SDI global score. Flare incidence and severity were also assessed. The main comparison groups for exploratory efficacy outcomes were patients who received SAPHNELO 300 mg or placebo in the TULIP trials and continued the same treatments throughout the LTE study (combined SAPHNELO 300 mg [n=358] versus combined placebo [n=178] groups, respectively).^16,25

LTE STUDY KEY LIMITATIONS: Study was not powered for statistical comparison of safety or efficacy between groups and the duration of study may not capture rare events with longer latency periods; data regarding elderly patients are limited and pregnant patients were excluded; potential selection bias (only patients completing a TULIP study were eligible); survival bias (no imputation was performed for patients who discontinued and/or received additional immunosuppressants); and efficacy data could be biased based on patient withdrawals related to SLE flares.¹⁶

A 52-week, multicenter, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of SAPHNELO administered subcutaneously in adults with SLE. Eligible patients were ≥18 years old with moderate to severe disease (SLEDAI-2K ≥6), organ involvement as assessed by BILAG, and a PGA score ≥1, while receiving stable doses of standard SLE therapy (OCS, antimalarials, and/or immunosuppressants) at baseline. Patients continued their existing SLE therapy at stable doses throughout the study, except for OCS (prednisone or equivalent), which was tapered per protocol in those receiving ≥10 mg/day at baseline. Patients with active lupus nephritis or severe central nervous system lupus were excluded.

Patients were randomized 1:1 to receive 120 mg anifrolumab-fnia or placebo via subcutaneous injection every week, stratified by baseline SLEDAI-2K score (<10 vs ≥10 points), OCS dose (<10 mg/day vs ≥10 mg/day prednisone or equivalent), and IFNGS status (high vs low). The primary endpoint was the proportion of patients achieving a BICLA response at Week 52. A pre-specified interim analysis was conducted after 220 patients had completed Week 52 or withdrawn from the trial.^2,26

MUSE was a 52-week, Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 305 adult patients with moderately to severely active SLE who were randomized (1:1:1) to SAPHNELO 300 mg (N=99), anifrolumab 1000 mg (N=104), or placebo (N=102), administered IV Q4W. Patients were also receiving ST at stable doses (either one or any combination of antimalarials, immunosuppressants, or OCS). Tapering of OCS was encouraged but was at the discretion of the investigators. Patients had seropositivity for antinuclear antibodies and/or anti-dsDNA and/or anti-Sm antibodies; SLEDAI-2K score of ≥6 (excluding points from lupus headache or organic brain syndrome); clinical SLEDAI-2K score of ≥4 (excluding points from laboratory results); BILAG-2004 organ domain scores of ≥1 A or ≥2 B items; and a PGA of score ≥1. Patients were stratified by IFNGS test status (high or low), SLEDAI-2K score (<10 or ≥10), and OCS dosage (<10 mg/day or ≥10 mg/day). The primary endpoint was a combined assessment of SRI-4 response rate and sustained reduction in OCS (<10 mg/day and ≤ OCS dose at Week 1, sustained for 12 weeks) measured at Week 24.²⁷

A multinational, prospective, observational study assessing the effectiveness of SAPHNELO in patients with SLE in routine clinical practice. The objective of this interim analysis is to evaluate the effects of SAPHNELO treatment on DORIS remission (and LLDAS) attainment in patients with SLE from the first 6 months of the ASTER study. Eligible adults with SLE were enrolled at routine clinical visits before the first SAPHNELO infusion date (index) and started SAPHNELO treatment per the approved country-specific label at study sites.¹²

ASTER STUDY KEY LIMITATIONS: The patient population was restricted to those with moderate to severe SLE initiating SAPHNELO treatment, and the requirement for a smartphone and mobile application for patient-reported outcomes excluded patients without the necessary technology or willingness to use it. The extended 3-year follow-up period introduced a risk of patient attrition, potentially affecting data completeness, especially in later time points. Finally, as a single-arm observational study, ASTER lacks a control group, which prevents causal inferences regarding the effectiveness of SAPHNELO and only allows for the observation of outcome changes among patients who began treatment.¹³

A real-world evidence, retrospective, observational cohort study of SAPHNELO-treated adult patients with SLE from the American Rheumatology Network, a consortium of US community rheumatology practices. Eligible patients included those aged ≥18 years at anifrolumab initiation (index); ≥6 months of medical history before index; ≥12 months of follow-up post-index; ≥6 infusions within 12 months post-index and receiving OCS therapy. Observation periods included baseline (6 months prior to index), follow-up period 1 (0-6 months post-index), and follow-up period 2 (>6-12 months post-index). Outcome measures included mean daily OCS dose (or prednisone equivalent) for days supplied, proportion of patients receiving OCS, mean daily OCS dose >5 mg/≤5 mg or >7.5 mg/≤7.5 mg, and clinical disease assessments (SLEDAI-2K, complement C3/C4).^19,20

SPIREA STUDY KEY LIMITATIONS: Data are limited by accuracy and completeness of input at the provider level into the care-management tools at the source (eg, EMR, infusion logs, and medical claims) and by actual practice (ie, individual providers may not conduct labs, disease assessments, etc, as regularly or at all compared with other providers).^19,20

A retrospective study that compared patients who initiated SAPHNELO 300 mg IV Q4W + ST in TULIP-1 and TULIP-2, the SAPHNELO + ST arm (n=354), with similar patients in the UTLC who received real-world standard of care, the RW ST arm (n=561). For SAPHNELO + ST, ST included OCS, antimalarials, and immunosuppressants. Patients were not allowed to initiate new antimalarials or immunosuppressants, and dosage was required to remain stable through Week 52. Oral corticosteroids were tapered per TULIP trial protocols in all patients with baseline OCS ≥10 mg/day. For RW ST, ST included OCS, antimalarials, and immunosuppressants, without restriction on dosage or length of treatment. All eligible patients who initiated 300 mg of SAPHNELO in TULIP-1 or TULIP-2 were included in the SAPHNELO + ST arm (regardless of subsequent enrollment in the LTE study). Patients in the RW ST arm were included if they met key eligibility criteria from TULIP-1 and TULIP-2.²¹

Patients in the SAPHNELO + ST arm were indexed at SAPHNELO initiation and followed until the earliest occurrence of death, loss to follow-up, or Week 208 assessment in the LTE study. Patients in the RW ST arm were indexed at the first instance of meeting all eligibility criteria, in which they were receiving ≥1 eligible SOC treatment (their “index assessment”) and followed until the earliest occurrence of death, loss to follow-up, or end of the treatment study period. The primary endpoint was change in SDI from index date to Week 208. Secondary endpoint was time to first SDI progression.²¹

LASER STUDY KEY LIMITATIONS: The study used propensity score methods instead of a randomized trial design; differential outcome misclassification could affect results due to the combination of trial and RW data sources; changes in SOC over time could also affect study results; while the SAPHNELO and RW SOC arms were balanced at baseline, balance was not guaranteed during follow-up; more proactive attention to glucocorticoid sparing has been a feature of more recent SLE management guidelines which may have influenced results; the possibility of residual confounding cannot completely be excluded as there were temporal improvements in the screening and management of key comorbidities such as hypertension, hyperlipidemia, and bone protection.²¹