Lupus Science & Medicine
Flare rate was numerically lower with anifrolumab versus placebo in both IS subgroups (rate ratio (RR) estimate, IS-inexperienced, 0.64, 95% CI 0.40 to 1.01, p=0.055; IS-experienced, 0.80, 0.61–1.04, p=0.097). Annu- alised flare rates were generally lower in IS-inexperienced patients (estimate, anifrolumab 0.38, 95% CI 0.26 to 0.56; placebo 0.59, 0.41–0.85) versus IS-experienced patients (estimate, anifrolumab 0.58, 0.45 to 0.74; placebo 0.72, 0.56–0.92). As shown in figure 3A, observed mean daily GC doses decreased from baseline through week 32 in IS-in- experienced patients or week 40 in IS-experienced patients. Thereafter, in the anifrolumab groups, mean GC dosages increased slightly from weeks 40 to 52 in IS-inexperienced patients (n=113 at all timepoints) and from weeks 44 to 52 in IS-experienced patients (week 44, n=206; week 48, n=203; week 52, n=199), though the mean daily GC dosages (any group) did not return to the levels required at baseline. At week 52, mean (SE) GC dosage was numerically higher with anifrolumab versus placebo in IS-inexperienced patients (n=113, 6.0 (0.73) mg/day vs n=107, 5.8 (0.61) mg/day) and numerically lower versus placebo in IS-experienced patients (n=199, 5.2 (0.45) mg/day vs n=195, 6.5 (0.50) mg/day). Three patients with baseline daily GC dosages >40 mg/day were excluded from these analyses (all treated with anifrolumab; one IS-inexperienced, two from the IS-ex- perienced group). Among patients with GC ≥ 10 mg/day at baseline, numerically more IS-inexperienced patients treated with anifrolumab maintained GC reduction at week 52 vs IS-experienced patients (58.0% (40/69) vs 46.8% (56/121)) (figure 3B). Treatment differ- ence favoured anifrolumab versus placebo in both IS subgroups (IS-inexperienced, Δ =24.3, 95% CI 8.1 to 40.6, p=0.0033; IS-experienced, Δ =16.0, 95% CI 3.6 to 28.4, p=0.0113). In patients treated with anifrolumab, rates of any AE (86.6% vs 89.3%), any serious AE (SAE; 13.4% vs 9.9%), and any AE leading to discontinuation (4.7% in both groups) were similar in both IS subgroups (IS-inexperienced, n=127; IS-experienced, n=233). However, rates of any treatment- related AEs or AESI were lower in IS-inexperienced patients versus IS-experienced patients receiving anifrolumab (treatment-related AEs, 27.6% vs 42.1%; AESIs, 7.1% vs 15.9%) (table 2). Rates of herpes zoster AESIs were lower among IS-inexperienced versus IS-experienced patients treated with anifrolumab (1.6% vs 9.0%). Among IS-inexpe- rienced patients, rates of any AESI were lower following treat- ment with anifrolumab than treatment with placebo (7.1% (9/127) vs 8.5% (11/130), respectively). A slightly lower percentage of infections and infestations was seen in IS-in- experienced vs IS-experienced patients (anifrolumab, 66.9% (85/127) vs 74.2% (173/233); placebo, 53.8% (70/130) vs 60.2% (142/236]) (table 3). DISCUSSION Patients with an inadequate response to antimalarials and GCs are frequently prescribed IS by treating physicians;
however, biologic treatments are now included in treat- ment recommendations without the requirement for prior IS failure. 3 15 According to the 2023 EULAR recom- mendations, 3 there are three options for treating patients who do not respond to HCQ alone or in combination with GCs, or who are unable to taper GCs: (1) add conventional IS first and a biologic at a later time if the patient does not achieve the target; (2) add biologic first and conventional IS at a later time if the patient does not achieve the target; or (3) treat with a combination of a biologic and IS simul- taneously. Combination therapy should be reserved for patients with more severe, non-renal SLE, 3 but in some patients with less severe non-renal SLE, a conventional IS or a biologic may be sufficient. Notably, phase 3 RCTs showed that the addition of biologics to standard therapy was more effective than placebo plus standard therapy in achieving the study endpoints; however, the standard therapies in these RCTs consisted of GCs, antimalarial agents and, in more than 40% of cases, IS. 4–6 8 16 RCTs of biologic agents were not stratified by prior IS expo- sure, and IS treatment history was not considered in the comparisons of biologics with placebo. The aim of this study was to evaluate the efficacy and safety of anifrolumab in patients with moderate-to-severe SLE who had a treatment history of antimalarials and/ or oral GCs but no reported history of IS use since SLE diagnosis. At week 52 of the TULIP-1/TULIP-2 treatment period, a higher proportion of patients attained DORIS remission with anifrolumab versus placebo regardless of IS history; the improved rates of DORIS remission with anifrolumab were nominally significant in both IS-inex- perienced and IS-experienced patients. Together, those DORIS remission rates favoured anifrolumab over placebo regardless of IS subgroup and were greater in IS-inexpe- rienced versus IS-experienced patients, supporting the efficacy of anifrolumab in treat-to-target approaches for SLE management in patients with inadequate response to antimalarials and/or GCs, even without history of IS treatment failure. 3 Similar results were seen for BICLA response, favouring anifrolumab over placebo, regardless of IS experience. LLDAS, LLDAS-5, CLASI-50 and SRI(4) response rates were also numerically higher with anifrolumab versus placebo, regardless of IS experience, although the differ- ences favouring anifrolumab reached nominal signifi- cance only for IS-experienced patients. Numerically more patients with GC ≥ 10 mg/day at baseline achieved and maintained GC reduction with anifrolumab in the IS-in- experienced versus the IS-experienced group; the treat- ment difference favoured anifrolumab versus placebo in both subgroups. Anifrolumab treatment numerically reduced annu- alised flare rates versus placebo in patients in both IS subgroups. Regardless of study treatment, IS-inexperi- enced patients generally had fewer flares compared with IS-experienced patients. This aligns with expectations based on the lower rate of IFNGS-high status among IS-inexperienced patients and the positive association
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Doria A, et al . Lupus Science & Medicine 2026; 13 :e001891. doi:10.1136/lupus-2025-001891
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