Takako Hashimoto*
Hidekata Yasuoka
- Division of Rheumatology, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan
Background: Anifrolumab, a monoclonal antibody against the type I interferon receptor, has shown efficacy in systemic lupus erythematosus (SLE). However, sustained remission after drug discontinuation has been rarely reported.
Case presentation: We reported two females with SLE who achieved biologic-free clinical remission after discontinuation of anifrolumab, with no major adverse events observed during or after treatment. Case 1: A 25-year-old woman with newly diagnosed SLE presented with active disease (SLEDAI-2K 14), including arthritis, facial rash, alopecia, mucosal ulcers, hypocomplementemia, and anti–double-stranded DNA antibody positivity. She was initially treated with prednisolone (PSL) and hydroxychloroquine (HCQ); however, a flare occurred during glucocorticoid (GC) tapering, and anifrolumab was initiated with concomitant methotrexate (MTX). The patient achieved clinical remission according to the Definition of Remission In SLE (DORIS) criteria, despite persistent hypocomplementemia and anti–dsDNA antibody positivity. After sustained remission, PSL was discontinued, MTX was tapered, and anifrolumab was discontinued after 25 months due to sustained clinical remission according to the DORIS criteria and patient preference related to work-related difficulty with long-term regular follow-up. She has remained in clinical remission for 6 months on HCQ and low-dose MTX. Case 2: A 22-year-old woman with SLE diagnosed at age 16 presented after disease relapse following GC withdrawal at age 21. At relapse, her disease activity was moderate (SLEDAI-2K 11), characterized by facial rash, alopecia, mucosal ulcers, leukopenia, hypocomplementemia, and anti–dsDNA positivity. She was treated with anifrolumab in combination with HCQ. Her disease activity achieved and maintained clinical remission according to the DORIS criteria, despite persistent hypocomplementemia and anti–dsDNA antibody positivity. Dose spacing and subsequent discontinuation of anifrolumab were attempted because of patient preference related to work-related limitations to long-term follow-up, and future pregnancy plans, and sustained remission was maintained. Even after switching to tacrolimus (Tac), she has maintained remission without anifrolumab for 12 months.
Conclusion: These cases suggested that clinical remission could be maintained after discontinuation of anifrolumab in selected patients with SLE.
1 Introduction
Anifrolumab is a fully human monoclonal antibody targeting the type I interferon receptor subunit 1 and has demonstrated efficacy in reducing disease activity and GC dependence in patients with moderate-to-severe SLE, as shown in the TULIP-1 and TULIP-2 trials (1). Long-term extension studies have further supported its sustained clinical benefit and acceptable safety profile during continued treatment (2). However, evidence regarding clinical outcomes after discontinuation of anifrolumab remains extremely limited.
In clinical practice, treatment de-escalation has become an important therapeutic option in SLE, particularly for patients who achieve sustained remission. While GC tapering and withdrawal are well-established treatment goals because of the GC toxicity, discontinuing biologics in patients with stable disease has been under the discussion. The concept of biologic-free remission may be clinically relevant, especially for young women, because of therapeutic decision-making based on the patients' preference.
Here, we reported two young women with relapsing SLE who achieved sustained clinical remission after discontinuation of anifrolumab, following prolonged disease control during treatment. Importantly, both of the patients maintained remission for 6–12 months after anifrolumab withdrawal while receiving only conventional immunomodulatory therapy, without experiencing disease flare or adverse events. These cases might provide preliminary clinical observations suggesting that, in carefully selected patients, stepwise de-escalation of biologics after sustained remission could be an option.
The clinical courses of the two patients and the timing of treatment modifications are summarized in Figure 1.
Figure 1. (A) Clinical course of Case 1. (B) Clinical course of Case 2.
2 Case description
2.1 Case 1
A 25-year-old woman was diagnosed with SLE in April 2023. At disease onset, she presented with fever, arthritis, facial rash, alopecia, mucosal ulcers, hypocomplementemia, and anti-dsDNA antibody positivity. Her SLEDAI-2K score was 14, indicating moderate disease activity.
She was started on HCQ at 200 and 400 mg on alternating days and PSL 20 mg/day. Her disease activity rapidly improved, with a decrease in the SLEDAI-2K score to 4 reflecting persistent anti-dsDNA antibody positivity and hypocomplementemia, and fulfilling clinical remission according to the Definition of Remission In SLE (DORIS) criteria. Based on the response, PSL was tapered to 15 mg/day on April 28 and further to 8 mg/day on May 12, 2023. However, she experienced disease relapse with arthritis and malar rash. A SLEDAI-2K score was 10, requiring re-escalation of PSL to 20 mg/day on May 19, 2023.
To achieve sustained disease control, intravenous anifrolumab 300 mg every 4 weeks was initiated on May 26, 2023, followed by the addition of 8 mg/week MTX on June 9, 2023. Her disease activity improved again, and on August 5, 2023, she re-achieved clinical remission according to the DORIS criteria, with a SLEDAI-2K score of 4 attributable to persistent serological activity alone. PSL was subsequently tapered to 7.5 mg/day.
After sustained DORIS remission, complete discontinuation of PSL was possible on August 27, 2024. Due to mild nausea, MTX was reduced to 6 mg/week on November 19, 2024, and further to 4 mg/week on March 14, 2025. Despite dose reductions, the patient maintained clinical remission according to the DORIS criteria. Following shared decision-making, anifrolumab was discontinued in June 2025, 25 months after initiation, primarily due to the patient's preference and difficulty attending long-term regular hospital visits because of a demanding work schedule. Clinical and laboratory parameters before initiation of anifrolumab and at the time of treatment discontinuation in Case 1 are summarized in Table 1.
Table 1. Clinical and laboratory parameters before initiation and at discontinuation of anifrolumab in case 1 and case 2.
As of December 2025, she has maintained clinical remission according to the DORIS criteria on 200 mg/day HCQ and 4 mg/week MTX, even without relapse or adverse events following discontinuation of anifrolumab.
2.2 Case 2
A 22-year-old woman with SLE presented to our department because of disease relapse. She was initially diagnosed with SLE at age 16 in 2016, presenting with facial rash, arthritis, leukopenia, hypocomplementemia, and anti-dsDNA antibody positivity and was treated with GC. Because of remission, GC was withdrawn at age 21. She was also positive for lupus anticoagulant and anticardiolipin IgG antibodies with prolonged activated partial thromboplastin time; although no thrombotic events were observed, low-dose aspirin was prescribed prophylactically. After the visit, HCQ was started at 200 and 400 mg on alternating days and PSL 50 mg/day. Since her disease activity was improved, dose of PSL was gradually tapered and discontinued in September 2021. At that time, she maintained clinical remission with a SLEDAI-2K score of 2 due to persistent anti-dsDNA antibody positivity, fulfilling clinical remission according to the DORIS criteria.
After GC withdrawal, she developed disease relapse characterized by malar rash, alopecia, mucosal ulcers, leukopenia, hypocomplementemia, and anti-dsDNA antibody positivity, and referred to our department on December 28, 2021. At the relapse, her SLEDAI-2K score was 11 indicating moderate disease activity. However, she was not willing to re-introduce GC, anifrolumab was initiated on January 11, 2022, in combination with HCQ.
Three months after initiation of anifrolumab, improvement in malar rash and alopecia was observed. By July 2022, her disease activity was improved to a SLEDAI-2K score of 4, reflecting persistent anti-dsDNA antibody positivity and hypocomplementemia. Further improvement was noted by January 24, 2023, when her SLEDAI-2K score decreased to 2 due to anti-dsDNA antibody positivity alone, maintaining clinical remission according to the DORIS criteria. Based on sustained disease control, dose spacing of anifrolumab was initiated on February 2, 2024, extending the dosing interval from every 4 weeks to every 6 weeks.
Following shared decision-making, anifrolumab was discontinued on October 29, 2024, primarily due to the patient's preference, difficulty attending long-term regular follow-up because of a demanding work schedule, and future pregnancy planning. 1.5 mg/day Tac was subsequently introduced on December 10, 2024. On February 4, 2025, her SLEDAI-2K score was increased to 4 reflecting persistent anti-dsDNA antibody positivity and hypocomplementemia, but she continued to fulfill clinical remission according to the DORIS criteria. As of December 2025, she has been maintained clinical remission according to the DORIS criteria with HCQ and low-dose Tac without clinical relapse or adverse events following discontinuation of anifrolumab. Clinical and laboratory parameters before initiation of anifrolumab and at the time of treatment discontinuation in Case 2 are summarized in Table 1.
3 Timeline
The clinical course of Case 1 is shown. The timing of intravenous anifrolumab administration is indicated by blue arrows. The doses of HCQ, MTX, and PSL are shown as bars. In the graph, the dotted line represents the C3 level (mg/mL), the dashed line represents the anti-double-stranded DNA (dsDNA) antibody titer (IU/mL), and the solid line represents the SLEDAI-2K score. HCQ: hydroxychloroquine, MTX: Methotrexate, PSL: Prednisolone
The clinical course of Case 2 is shown. The timing of intravenous anifrolumab administration is indicated by blue arrows. The doses of HCQ and Tac are shown as bars. In the graph, the dotted line represents the C3 level (mg/mL), the dashed line represents the anti-double-stranded DNA (dsDNA) antibody titer (IU/mL), and the solid line represents the SLEDAI-2K score. HCQ: hydroxychloroquine, Tac: Tacrolimus.
4 Discussion
Reports describing sustained clinical remission after discontinuation of anifrolumab in SLE have been extremely limited. In this report, we showed two young women with SLE achieved and maintained biologic-free clinical remission for 6–12 months following anifrolumab discontinuation, without experiencing adverse events during treatment or follow-up. These cases provide insight into potential treatment de-escalation strategies in selected patients with well-controlled disease.
Accumulating evidence shows a role of aberrant activation of innate immunity, particularly type I interferon signaling, in the pathogenesis of SLE (3). Interferon signaling is considered an upstream driver of immune dysregulation, making it an attractive therapeutic target. Anifrolumab has been shown to suppress interferon-stimulated gene expression and modulate peripheral immune cell subsets during treatment (1, 2, 4). However, although sustained clinical remission was observed after discontinuation of anifrolumab in these patients, it remains difficult to attribute this outcome to an immunologic “reset.” Therefore, our findings should not be overinterpreted, and further basic and translational investigations are needed.
There are various approaches after achieving remission. We usually consider the cessation of GC at first and then discontinuation of immunosuppressants or that of biologics are also possible. Usually, discontinuation of immunosuppressants is due to side-effects caused by the long-term use or the future pregnancy. On the other hands, discontinuation anifrolumab prior to other immunomodulatory agents might be due to patient preference, practical considerations, economic reasons, and side-effects. In our cases, the decision to withdraw the biologic was strongly based on each patient preference based on shared-decision making in addition to the maintenance of clinical remission according to the DORIS criteria. In precise, practical considerations such as difficulty attending regular hospital visits due to demanding work schedules and future pregnancy planning played a significant role in these cases. These considerations are particularly relevant in young women and align with treat-to-target principles in SLE, which emphasize sustained remission with the lowest effective treatment burden.
Notably, both patients continued background therapy with HCQ, with or without low-dose MTX or Tac, after anifrolumab discontinuation. Maintenance of such conventional immunomodulatory therapy might contribute to immune stability and prevention of disease flare. In Case 2, prophylactic introduction of low-dose Tac was intended to minimize relapse risk, suggesting that treatment de-escalation might give a better disease control compared with the abrupt withdrawal of anifrolumab.
The absence of adverse events during and after anifrolumab therapy in these cases might be related to patient-specific factors, including young age, absence of significant comorbidities, and concomitant HCQ use, which is associated with reduced infection risk in SLE (5). However, no definitive concerns for the safety were shown in these cases.
Since this is a case report, several limitations had to be accepted. This report describes only two cases, precluding generalization and causal inference. Follow-up duration after biologic withdrawal remains limited, and interferon signatures were not longitudinally assessed. Furthermore, optimal criteria for selecting candidates for biologic discontinuation remain undefined.
Despite these limitations, our observations suggested that, in selected patients, particularly younger women with sustained clinical remission and ongoing background therapy, a stepwise de-escalation of anifrolumab might be possible. Prospective studies with longer follow-up, standardized remission definitions, and longitudinal immunologic monitoring are needed to identify predictors of successful biologic withdrawal and to establish safe de-escalation strategies in SLE (6).
5 Patient perspective
Case 1: Because my SLE is stable, I am now able to lead my social life with hope and confidence, without being limited by ongoing treatment. I feel reassured knowing that my disease remains stable without the use of glucocorticoids or anifrolumab.
Case 2: I am now able to engage in my social and professional life without being constrained by treatment or its side effects, including during my job search. I feel relieved that my disease remains stable without the use of glucocorticoids or anifrolumab.
6 Conclusion
These two case reports illustrate that clinical remission achieved with anifrolumab could be maintained after its discontinuation in selected patients with SLE. Both patients sustained biologic-free clinical remission for 6–12 months after withdrawal of anifrolumab, without experiencing adverse events during treatment or follow-up. Importantly, although serological activity such as persistent anti-dsDNA antibody positivity and hypocomplementemia remained, both patients continued to fulfill clinical remission according to the DORIS criteria, which permit persistent serological abnormalities in the absence of clinical disease activity.
While these observations are limited by the small number of cases, they suggest that stepwise de-escalation of biologic therapy after sustained remission might be feasible in selected patients, particularly young women with stable clinical disease receiving appropriate background therapy. Further prospective studies are needed to define optimal patient selection, long-term outcomes, and safe strategies for treatment de-escalation in SLE.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Ethics statement
Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
TH: Conceptualization, Data curation, Investigation, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing. HY: Conceptualization, Supervision, Writing – review & editing.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Keywords: anifrolumab, biologic-free remission, de-escalation strategy, interferon blocking agents, systemic lupus erythematosus
Citation: Hashimoto T and Yasuoka H (2026) Case Report: Biologic-free clinical remission following anifrolumab discontinuation in systemic lupus erythematosus—two-case reports. Front. Lupus 3:1737535. doi: 10.3389/flupu.2025.1737535
Received: 2 November 2025; Revised: 28 December 2025;
Accepted: 29 December 2025;
Published: 14 January 2026.
Edited by:
Charalampos Skarlis, University of Nicosia, CyprusReviewed by:
Yusuke Miyazaki, University of Occupational and Environmental Health, JapanChiara Cardelli, University of Pisa, Italy
Copyright: © 2026 Hashimoto and Yasuoka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Takako Hashimoto, dGFrYWtvLWtAZnVqaXRhLWh1LmFjLmpw