POS0024 IMPROVEMENT OF HEMATOLOGICAL PARAMETERS DURING LONG-TERM ANIFROLUMAB TREATMENT AND ASSOCIATION WITH WEEK 52 BICLA RESPONSE
Authors: E. M. Vital, Z. Amoura, K. C. Kalunian, I. N. Bruce, Y. Tanaka, S. Manzi, I. Hupka, J. Knagenhjelm, H. Al-Mossawi, C. Lindholm
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Anifrolumab, a type I interferon receptor antibody, is approved for adults with moderate to severe systemic lupus erythematosus (SLE).[1] The phase 3, placebo-controlled TULIP-1/-2 and long-term extension (LTE) trials demonstrated the safety and efficacy of anifrolumab.[2] Lymphopenia, anemia, and thrombocytopenia are associated with increased disease activity and damage accrual in patients with SLE.[3-5] <h3>Objectives:</h3> (a) To evaluate normalization of lymphocytes, hemoglobin [Hb], and platelets, and (b) to investigate their association with British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response, in the TULIP-1/-2 and LTE trials. <h3>Methods:</h3> Adults with moderate to severe SLE despite standard therapy who received treatment in the 52-week TULIP-1/-2 feeder trials (NCT02446912, NCT02446899) could re-enroll in the 3-year LTE study (NCT02794285).[2] Included patients were randomized to receive intravenous anifrolumab 300 mg or placebo in both TULIP-1/-2 and the LTE. The percentages of patients with low, normal, or high levels of lymphocytes, Hb, and platelets were analyzed post hoc from Weeks 0–208. Low vs normalized levels were defined as &lt;1 GI [10<sup>9</sup> cells]/L vs ≥1 GI/L–&lt;4 GI/L for lymphocytes, &lt;120 g/L vs ≥120 g/L for Hb, and &lt;150 GI/L vs ≥150 GI/L–&lt;450 GI/L for platelets. Normalization of lymphocytes, Hb, and platelets from baseline were analyzed agnostic to treatment group in relation to BICLA response [6] at Week 52. <h3>Results:</h3> Among the 536 patients randomized to anifrolumab 300 mg (n=358) or placebo (n=178) in TULIP-1/-2 and the LTE study, similar proportions of anifrolumab- and placebo-treated patients had low baseline lymphocytes (38.5%, n=138 vs 41.6%, n=74), Hb (32.1%, n=115 vs 28.7%, n=51), or platelets (10.6%, n=38 vs 9.0%, n=16). At Week 52, lymphocytes normalized in a higher proportion of anifrolumab-treated patients versus placebo (51.4%, n=71 vs 21.6%, n=16; Figure 1). This trend was seen by Week 12 and was maintained through Week 208 (39.9%, n=55 vs 12.2%, n=9). A higher proportion of anifrolumab-treated patients had normalized Hb compared with placebo (Week 52: 26.1%, n=30 vs 17.6%, n=9; Week 208: 27.0%, n=31 vs 13.7%, n=7). Similar proportions of patients had normalized platelets in the anifrolumab and placebo groups (Week 52: 44.7%, n=17 vs 43.8%, n=7; Week 208: 34.2%, n=13 vs 31.3%, n=5). Withdrawal rates at Week 208 were lower in the anifrolumab versus placebo groups for patients who had low lymphocytes (Figure 1), Hb, or platelets at baseline (lymphocytes: 35.5%, n=49 vs 54.1%, n=40; Hb: 35.7%, n=41 vs 54.9%, n=28; platelets: 36.8%, n=14 vs 50.0%, n=8). Among all patients with low baseline levels, irrespective of treatment group, normalization (low to normal/high) of lymphocytes, Hb, and platelet levels at Week 52 was associated with Week 52 BICLA response (normalization in responders vs nonresponders, lymphocytes: 56.1% [64/114] vs 33.8% [44/130]; Hb: 33.0% [31/94] vs 20.2% [22/109]; platelets: 57.6% [19/33] vs 40.0% [12/30]). During the LTE, the percentage of patients with normalized lymphocytes remained higher among Week 52 BICLA responders vs nonresponders (Week 208: 76.5% [62/81] vs 50.9% [28/55]); a similar trend was not seen for Hb or platelets. <h3>Conclusion:</h3> Patients receiving long-term anifrolumab treatment were more likely to normalize their SLE-related lymphopenia and anemia compared with placebo (ie, standard therapy alone). Irrespective of treatment group, Week 52 BICLA response was associated with normalization of lymphocytes, Hb, and platelets. Anifrolumab treatment may confer long-term clinical benefits through reduction of lymphopenia-related risks and through improved fatigue associated with anemia. <h3>REFERENCES:</h3> [1] SAPHNELO (anifrolumab) Prescribing Information. AstraZeneca; 2023. [2] Kalunian KC. <i>Arthritis Rheumatol</i>. 2023;75:253–265. [3] Bertoli AM. <i>Rheumatol (Oxford</i>). 2007;46:1471–1476. [4] Vilá LM. <i>Arthritis Rheum.</i> 2006;55:799–806. [5] Zhao H. <i>Platelets</i>. 2010;21:380–385. [6] Morand EF. <i>N Engl J Med</i>. 2020;382:211–221. <h3>Acknowledgements:</h3> This study was sponsored by AstraZeneca. Writing assistance was provided by Vasileios Stamou, PhD, and Rosie Butler, PhD, of JK Associates Inc., part of Avalere Health, and funded by AstraZeneca. <h3>Disclosure of Interests:</h3> Edward M. Vital Speakers bureau: AstraZeneca, Lilly, Novartis, Otsuka, UCB, Consultant of: Abbvie, AstraZeneca, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support (paid to employer) from: AstraZeneca, Sandoz, Zahir Amoura Grant/research support from: Amgen, AstraZeneca, GlaxoSmithKline, Kezar, Novartis, Roche, Kenneth C. Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Equilliumbio, Genentech/Roche, GlaxoSmithKline, Kezarbio, Merck, Grant/research support from: Amgen, Lupus Foundation of America, Lupus Research Alliance, NIH, Novartis, UCB, Ian N. Bruce Speakers bureau: AstraZeneca, GlaxoSmithKline, Janssen, UCB, Consultant of: AstraZeneca, Aurinia, Dragonfly Therapeutics, GlaxoSmithKline, Horizon Therapeutics, Lilly, Takeda, UCB, Grant/research support from: AstraZeneca, GlaxoSmithKline, Janssen, Novartis, Yoshiya Tanaka Speakers bureau: Abbvie, Asahikasei, AstraZeneca, Behringer-Ingelheim, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Pfizer, Taiho, Taisho, Grant/research support from: Asahikasei, Chugai, Eisai, Mitsubishi-Tanabe, Taisho, Susan Manzi Consultant of: AstraZeneca, Cartesian, Cuegene, Exagen, GlaxoSmithKline, Lilly, Grant/research support from: AstraZeneca, Cartesian, Cuegene, Exagen, GlaxoSmithKline, Lilly, Ihor Hupka Employee of: AstraZeneca, Jacob Knagenhjelm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Hussein Al-Mossawi Speakers bureau: Novartis, Pfizer, UCB, Shareholder of: Bristol Myers Squibb, GlaxoSmithKline, UCB, Employee of: AstraZeneca (previous), UCB (previous), Immunocore (current), Consultant of: Abbvie, Novartis, Roche, Grant/research support from: UCB, Catharina Lindholm Shareholder of: AstraZeneca, Employee of: AstraZeneca.