Presentation, investigations and findings
A 24-year-old clerk and mother of two presented to our hospital in August 2010 with fever, malar rash on the face, vasculitic rash on the fingers and alopecia. Her medical and family histories were unremarkable.
Serological testing revealed elevated antinuclear antibodies (ANA) with titre 1:2560 and positive results for anti–double-stranded DNA (anti–dsDNA, >200 IU/mL) and anti-Smith antibodies. Antiphospholipid antibody testing indicated the presence of lupus anticoagulant, while anticardiolipin and anti-β2 glycoprotein 1 tested negative, and C3 and C4 complement levels were low. The 24-hour urine test showed a protein level of 0.11 g/day. The patient was diagnosed with systemic lupus erythematosus (SLE), characterized by mucocutaneous involvement, alopecia and active serological markers. Her SLE Disease Activity Index 2000 (SLEDAI-2K) score was 9.
Initial treatment and response
In September 2010, the patient was initiated on a treatment regimen that consisted of prednisolone, hydroxychloroquine (HCQ), and aspirin for primary thromboprophylaxis. Two weeks later, gradual tapering of prednisolone commenced, and azathioprine was added in January 2011. Her SLEDAI-2K score had improved to 4.
In subsequent years, the patient experienced multiple cutaneous flareups that required several courses of uptitrated prednisolone. Managing her rash was challenging when prednisolone doses were reduced to ≤10 mg daily; each flare-up required a step-up to a higher dose of prednisolone, which necessitated a more gradual tapering than before. Consequently, she developed Cushingoid features, episodes of recurrent chest infections and herpes zoster.
In September 2017, investigations revealed a urine protein-to-creatinine ratio (UPCR) of 5.16. Renal biopsy confirmed class IV lupus nephritis (LN), which was successfully managed with addition of mycophenolate mofetil, leading to UPCR reduction to 0.17 by February 2018.
Between July 2018 and July 2024, multiple attempts to control the rash and flare-ups using various combinations of conventional immunosuppressants were futile. Response also remained suboptimal with biologics (rituximab and belimumab) treatment. (Figure 1) Throughout these years, the patient had persistent rash and alopecia despite normalization of serological markers, and her SLEDAI-2K score remained at 4.
Treatment and outcomes with anti–IFN-α receptor mAb
Confronted with refractory rash and limited treatment options, the patient was started on anifrolumab (300 mg intravenously Q4W), supported by the Samaritan Fund, in July 2024. Notable improvement in both the rash and alopecia was observed after the initial dose. By the third dose, alopecia was nearly resolved, and the patient achieved a lupus low disease activity state (LLDAS), with the SLEDAI-2K score improving from 4 to 2.
After the fourth dose, the patient achieved remission, meeting the criteria in the Definitions of Remission In SLE (DORIS) and the British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA). There were no recurrences of rash despite prednisolone reduction to 5 mg daily. UPCR remained stable at 0.12 and no adverse events (AEs) were reported. (Figures 1–3)
During the last consultation in February 2025, the patient remained in remission, enjoying a good quality of life with well-controlled symptoms.
Discussion
In SLE, treat-to-target (T2T) strategy — aiming for remission or low disease activity when remission is not achievable — is crucial for preventing end-organ damage.1-3
According to 2023 recommendations from the European Alliance of Associations for Rheumatology (EULAR), SLE treatment should be individualized based on different considerations, such as clinical manifestations, severity of organ involvement and patient characteristics.2 Both the EULAR guidelines and our hospital’s algorithm designate HCQ as the mainstay therapy unless contraindicated. Glucocorticoid may be needed for controlling SLE activity and manifestations but are often associated with side effects. To minimize long-term risks, oral glucocorticoid should be maintained at ≤5 mg/day, and, if possible, withdrawn.2
Our patient experienced disease flares while on prednisolone <10 mg/day, requiring dose uptitration. Although oral conventional immunosuppressants and belimumab partially managed SLE activity, symptoms such as a malar rash, vasculitic rash and alopecia persisted. Prolonged glucocorticoid use further contributed to complications, including Cushingoid features, hypertension, and recurrent infections. Given the refractory rash despite normalized and stable serology, along with exhausted treatment options, our patient was initiated on anifrolumab.
Anifrolumab provides early and sustained reduction in SLE activity and facilitates glucocorticoid tapering in patients with moderate-to-severe disease.4,5 A pooled analysis of two phase III placebo controlled trials, TULIP-1 and TULIP-2, showed a higher BICLA response from week 8 with anifrolumab vs placebo (pnominal<0.001). This trend was observed in subsequent visits up to week 52.4 At week 52, BICLA response remained higher with anifrolumab vs placebo (47.5 vs 30.8 percent; difference, 16.6 percent; pnominal<0.001).5
Anifrolumab has a well-established safety profile. Common AEs included nasopharyngitis (16.3 percent), upper respiratory tract infection (15.5 percent), urinary tract infection (12.0 percent), bronchitis (9.8 percent), infusion-related reaction (9.4 percent) and herpes zoster (6.1 percent). To mitigate the risk of herpes zoster, vaccination can be considered before starting treatment.6
After the first dose of anifrolumab, our patient demonstrated a rapid response, with significant improvements in rash and alopecia. By the third dose, her SLEDAI-2K score improved from 4 to 2. By the fourth dose, glucocorticoid was tapered from 20–30 mg to 5 mg per day, and remission as defined by DORIS criteria was achieved. Notably, she tolerated anifrolumab well and did not experience any AEs during treatment.
According to 2023 EULAR guidelines, prior use of a conventional immunosuppressant is not mandatory before initiating approved biologics, including anifrolumab and belimumab. Early use of anifrolumab as an add-on after HCQ and steroid therapy may be considered for patients with moderate-to-severe non-renal SLE, particularly those with severe skin manifestations.2 Eligible patients may be covered by the Samaritan Fund. As demonstrated in clinical trials and our patient’s case, anifrolumab effectively controls disease activity, facilitates glucocorticoid tapering, and has a well-established safety profile.4-6
