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Background: Patients with cutaneous lupus erythematosus (CLE) experience disfiguring and painful lesions that can lead to psychological distress and significant impacts on quality of life. 1 Treatment of patients with systemic lupus erythematosus (SLE) with anifrolumab, a type I interferon receptor antagonist, was associated with CLE Disease Area and Severity Index–Activity (CLASI-A) improvements compared with placebo through Week 52 in the phase 3 TULIP-1 and TULIP-2 SLE trials. 2,3 CLASI assesses overall skin improvement and may be driven by erythema over the other components. 4
Objectives: To better understand the effect of anifrolumab on mucocutaneous SLE manifestations by analyzing the individual domains of CLASI-A using pooled data from the TULIP trials.
Methods: TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were randomized, double-blind, placebo-controlled, 52-week trials that evaluated efficacy and safety of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE despite standard therapy. 2,3 In a post hoc analysis, individual CLASI-A domains (erythema, scale/hypertrophy, alopecia, and mucosal) were assessed at Week 24 (time point chosen to ensure adequate duration for improvement in slow-remitting manifestations [eg, scale, alopecia]) in 2 patient subgroups: 1) the “chronic” mucocutaneous subgroup (resembling chronic/discoid CLE), defined as patients with a baseline erythema score ≥4 and scale score ≥2, and alopecia score ≥1 or baseline mucosal lesions or ulceration score of 1; and 2) the “extended” mucocutaneous subgroup (resembling all CLE subtypes), defined as patients who met the “chronic” criteria or those who had a baseline erythema score ≥8.
Results: Across the pooled TULIP trials, 360 patients received anifrolumab 300 mg and 366 patients received placebo. In patients with assessments at Week 24 in the “chronic” (anifrolumab n=58, placebo n=50) and “extended” (anifrolumab n=104, placebo n=96) subgroups, anifrolumab led to a greater mean percent reduction from baseline compared with placebo in erythema (chronic: −63.6% vs −39.9%; extended: −63.7% vs −41.2%) and scale/hypertrophy (chronic: −72.2% vs −42.6%; extended: −45.3% vs −7.3%). Anifrolumab-treated patients in both subgroups had no worsening in alopecia (chronic: 93.3% [56/60] vs 96.0% [48/50]; extended: 95.3% [102/107] vs 95.8% [92/96]) or mucous membrane (chronic: 95.0% [57/60] vs 96.0% [48/50]; extended: 96.3% [103/107] vs 94.8% [91/96]) from baseline vs placebo (
Skin Responses at Week 24 Compared With Baseline
| Criteria, n (%) | Chronic subgroup | Extended subgroup | ||
|---|---|---|---|---|
| Anifrolumab 300 mg (n=60) | Placebo (n=50) | Anifrolumab 300 mg (n=107) | Placebo (n=96) | |
| Erythema score reduction | ||||
| ≥25% | 53 (88.3) | 32 (64.0) | 93 (86.9) | 68 (70.8) |
| ≥50% | 42 (70.0) | 22 (44.0) | 71 (66.4) | 47 (49.0) |
| ≥60% | 34 (56.7) | 18 (36.0) | 61 (57.0) | 32 (33.3) |
| Scale/hypertrophy score reduction | ||||
| ≥10% | 49 (81.7) | 34 (68.0) | 55 (51.4) | 38 (39.6) |
| ≥25% | 47 (78.3) | 30 (60.0) | 53 (49.5) | 34 (35.4) |
| ≥50% | 46 (76.7) | 28 (56.0) | 51 (47.7) | 31 (32.3) |
| No new/worsened lesions in any individual body area | 44 (73.3) | 26 (52.0) | 81 (75.7) | 56 (58.3) |
| Alopecia | ||||
| ≥1-point decrease
| 25 (41.7) | 19 (38.0) | 35 (32.7) | 27 (28.1) |
| No worsening | 56 (93.3) | 48 (96.0) | 102 (95.3) | 92 (95.8) |
| Mucosal lesion/ulceration | ||||
| 1-point decrease
| 25 (41.7) | 13 (26.0) | 39 (36.4) | 23 (24.0) |
| No worsening | 57 (95.0) | 48 (96.0) | 103 (96.3) | 91 (94.8) |
a If baseline score ≥1.
b If baseline score =1.
Conclusion: In the phase 3 TULIP trials, SLE patients with mucocutaneous manifestations treated with anifrolumab experienced numerical improvements in erythema and scale/hypertrophy and no worsening in alopecia or mucous membrane CLASI-A domains compared with placebo, regardless of whether skin disease was classified by chronic or extended definitions. These encouraging data support further evaluation of anifrolumab in patients with CLE.
REFERENCES:
[1]Klein R. J Am Acad Dermatol. 2011;64:849–58.
[2]Furie RA. Lancet Rheumatol . 2019;1:e208–19.
[3]Morand EF. N Engl J Med. 2020;382:211–21.
[4]Albrecht J. J Invest Dermatol. 2005;125:889–94.
Acknowledgements: Writing assistance by Naomi Atkin (Fishawack Health). This study was sponsored by AstraZeneca.
Disclosure of Interests: Victoria Werth Consultant of: Celgene, Medimmune, Resolve, Genentech, Idera, Janssen, Lilly, Pfizer, Biogen, BMS, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Sorona, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kwoya Kirin, Regeneron, AstraZeneca, Abbvie, Octapharma, GSK, Cugene, UCB, Corcept, Beacon Bioscience, Rome Pharmaceuticals, Horizon, Merck, Kezar, Sanofi, Bayer, Akari, Grant/research support from: Celgene, Janssen, Pfizer, Biogen, Gilead, Corbus Pharmaceuticals, Genentech, AstraZeneca, Viela, Syntimmune, Amgen, Regeneron, Argenx, CSL Behring, Ventus, q32 Bio, BMS, Jenny Wissmar Shareholder of: AstraZeneca, Employee of: AstraZeneca, Anna Strömbeck Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca, Christi Kleoudis Shareholder of: AstraZeneca, Employee of: AstraZeneca, Marius Albulescu Shareholder of: AstraZeneca Ltd, Consultant of: UCB, Kymab Ltd, Employee of: AstraZeneca Ltd