Lupus Science & Medicine
Table 2 Safety overview, including SAEs, DAEs and AESIs, during treatment in IS-inexperienced and IS-experienced patients receiving anifrolumab or placebo in addition to standard therapy IS-inexperienced IS-experienced Anifrolumab 300mg (n=127) Placebo (n=130) Total (n=257) Anifrolumab 300mg (n=233) Placebo (n=236) Total (n=469) Any AE 110 (86.6) 95 (73.1) 205 (79.8) 208 (89.3) 201 (85.2) 409 (87.2) Any AE with outcome of death 1 (0.8) 0 1 (0.4) 1 (0.4) 0 1 (0.2) Any SAE* 17 (13.4) 19 (14.6) 36 (14.0) 23 (9.9) 42 (17.8) 65 (13.9) Any DAE 6 (4.7) 5 (3.8) 11 (4.3) 11 (4.7) 13 (5.5) 24 (5.1) Any treatment-related AE 35 (27.6) 32 (24.6) 67 (26.1) 98 (42.1) 63 (26.7) 161 (34.3) Any AE by maximum intensity Mild 61 (48.0) 45 (34.6) 106 (41.2) 80 (34.3) 95 (40.3) 175 (37.3) Moderate 37 (29.1) 44 (33.8) 81 (31.5) 113 (48.5) 84 (35.6) 197 (42.0) Severe 12 (9.4) 6 (4.6) 18 (7.0) 15 (6.4) 22 (9.3) 37 (7.9) Any AESI† 9 (7.1) 11 (8.5) 20 (7.8) 37 (15.9) 25 (10.6) 62 (13.2) Non-opportunistic serious infections 4 (3.1) 7 (5.4) 11 (4.3) 12 (5.2) 15 (6.4) 27 (5.8) Opportunistic infections 0 0 0 1 (0.4) 0 1 (0.2) Malignancy 0 0 0 3 (1.3) 3 (1.3) 6 (1.3) Herpes zoster 2 (1.6) 1 (0.8) 3 (1.2) 21 (9.0) 4 (1.7) 25 (5.3) TB (including latent TB) 0 0 0 2 (0.9) 1 (0.4) 3 (0.6) Influenza 2 (1.6) 4 (3.1) 6 (2.3) 4 (1.7) 4 (1.7) 8 (1.7) Major adverse cardiovascular events 1 (0.8) 0 1 (0.4) 0 0 0 *Including events with outcome of death. †AESI with no events during treatment in any group: anaphylaxis and vasculitis (non-SLE). AE, adverse event; AESI, AE of special interest; DAE, AE leading to discontinuation; IS, immunosuppressant; SAE, serious AE; SLE, systemic lupus erythematosus; TB, tuberculosis.
disease. This could have been related to the shorter time since SLE diagnosis and the lower rate of IFNGS-high status in this group. Less severe disease among IS-inexpe- rienced patients compared with IS-experienced patients could have contributed to the higher placebo response rates among these patients for some endpoints (LLDAS, LLDAS-5 and SRI-4) and may have driven the lack of nomi- nally significant differences between anifrolumab versus placebo in IS-inexperienced patients at week 52 for some outcomes. Higher baseline levels of antimalarial use and fewer months since SLE diagnosis in patients receiving placebo compared with those receiving anifrolumab within the IS-inexperienced group could also affect the differences between the treatments. Furthermore, the lower proportion of IFNGS-high patients at baseline in the IS-inexperienced vs IS-experienced group is expected to play an important role in SLE disease activity, progres- sion and treatment response, as well as the risk of flare. 17 18 Among patients treated with anifrolumab, IS-inexperi- enced patients were more likely to be able to maintain their GC dosage reduction to ≤ 7.5mg/day from baseline use ≥ 10 mg/day compared with those who had previously received IS, suggesting that anifrolumab may be a strong candidate to facilitate GC reduction in IS-naïve patients. However, the generally lower flare rates and less severe disease observed in IS-inexperienced patients could also explain the greater
number of patients able to maintain lower doses of GCs. In both groups, observed average GC doses decreased from baseline through week 36 and then increased slightly without returning to baseline levels. This increase may be explained in the IS-experienced group by patient attrition at the end of the study or, in both IS subgroups, by permitted exceptions to the requirement of stable GC dosages between weeks 40 and week 52, if patients with premature anifrolumab discontinua- tion, or patients prescribed GC to treat an AE. BICLA response rates favoured anifrolumab in both IS subgroups, while CLASI-50 response rates with anifrolumab were slightly lower in IS-inexperienced versus IS-experienced patients. One possible explanation is that combination treatment with anifrolumab and IS is more effective than anifrolumab alone for the treatment of more severe skin manifestations of SLE. Thus, the best treatment approach for patients with more severe skin or non-renal manifestations may be a combination of anifrolumab and IS, while anifrolumab without IS might be a better treatment option in patients with less severe skin manifestations or in patients with less severe non- renal SLE. Future studies are needed to examine these possibilities in greater detail. Anifrolumab was well tolerated regardless of IS history at baseline. Rates of AEs from any cause were lower with placebo in IS-inexperienced versus IS-experienced
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Doria A, et al . Lupus Science & Medicine 2026; 13 :e001891. doi:10.1136/lupus-2025-001891
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