Background: Achievement and maintenance of the Lupus Low Disease Activity State (LLDAS) are necessary for the long-term prevention of organ damage progression in patients with systemic lupus erythematosus (SLE); however, minor flares lower the achievement and maintenance rates, and consequent treatment changes such as glucocorticoid (GC) dose increase. Therefore, there is a demand for therapeutic strategies to control disease activity and achieve dose reduction or discontinuation of GCs using molecular targeted drugs.

Objectives: This study aimed to analyze the safety and efficacy of anifrolumab in patients with SLE who experience minor flares after achieving LLDAS in real-world clinical practice.

Methods: In this retrospective observational study, we assessed 65 SLE patients who experienced minor flares after achieving LLDAS. Of these, 30 were treated with the addition of glucocorticoids (GCs) or immunosuppressants, forming the standard of care (SoC) group. The remaining 35 patients were treated with the additon of only anifrolumab, constituting the anifrolumab group. Minor flare was defined as the revised Safety of Estrogens in Lupus Erythematosus National Assessment Flare Index. The LLDAS achievement rate at 26 weeks in the SoC and anifrolumab group were compared after adjusting with inverse probability of treatment weighting using propensity score (PS-IPTW).

Results: The retention rate of anifrolumab was 97.1% (34/35 patients) at week 26. No significant difference was observed in the patient background between the two groups after adjustment by PS-IPTW. There was no difference between the two groups in either the LLDAS achievement rate or the DORIS remission rate at week 12 after the onset of minor flares followed by treatment intensification. At week 26, the anifrolumab group had a higher the rate of LLDAS achievement (SoC: anifrolumab=53.3:85.7%, p=0.0042) and DORIS remission (SoC: anifrolumab=6.7:25.7 %, p=0.0412). The SoC group did not exhibit a significant decrease in GC dose at 26 weeks, while the anifrolumab group exhibited a significant decrease. GC doses at week 26 were lower in the anifrolumab group (SoC: anifrolumab=6.9±3.5: 3.1±3.8mg/day, prednisolone equivalent, p<0.0001). The incidence of adverse events were fewer in the anifrolumab group (p=0.0012), especially infections (p=0.0169).

Compared with patients treated for minor flares by GC dose increase (GC dose increase group, n=18) after adjustment by PS-IPTW, the anifrolumab group had a higher rate of LLDAS achievement (GC dose increase: anifrolumab=39.8:89.1%, p<0.0001) and DORIS remission (GC dose increase: anifrolumab=12.4:40.8%, p=0.0011). GC dose at week 26 was lower in the anifrolumab group (GC dose increase: anifrolumab=7.2±2.6:3.1±3.8 mg/day, prednisolone equivalent, p=0.0001). In anifrolumab group, three cases discontinued GC 26weeks after introduction of anifrolumab. The incidence of adverse events (p=0.0086) and infection (p=0.0442) were significant lower in the anifrolumab group.

Conclusion: The current study demonstrated the safety and efficacy of anifrolumab in patients with minor flares who once achieved LLDAS but had difficulty maintaining LLDAS. These findings suggested that disease activity could be improved by initiating anifrolumab therapy alone without GC dose increase in patients with minor flares. Anifrolumab may prevent the accumulation of disease-induced organ damage caused by SLE and drug-induced organ damage caused by GCs, thereby improving long-term QOL and prognosis in patients with SLE.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Yusuke Miyazaki Y.Miyazaki has received speaking feesfrom Bristol-Myers, Pfizer, GlaxoSmithKline, Astellas, Asahi-Kasei, and Boehringer Ingelheim., Shingo Nakayamada: None declared, Satoshi Kubo Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca. research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Satoshi Kubo has received research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Satsuki Matsunaga: None declared, Hiroaki Tanaka: None declared, Kentaro Hanami: None declared, Shunsuke Fukuyo: None declared, Yurie Satoh-Kanda: None declared, Yoshino Inoue: None declared, Yasuyuki Todoroki: None declared, Masanobu Ueno: None declared, Yoshiya Tanaka Y. Tanaka has received Speakers bureau from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Y. Tanaka has received Grant/research support from Mitsubishi-Tanabe, Eisai, Chugai, Taisho.